Literatur

Zuletzt geändert: 04.11.2024 https://kinderkrebsinfo.de/doi/e8952

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Autor(en)	Titel	Quelle
Gaartman AE, Sayedi AK, Gerritsma JJ, de Back TR, van Tuijn CF, Tang MW, Heijboer H, de Heer K, Biemond BJ, Nur E	Fluid overload due to intravenous fluid therapy for vaso-occlusive crisis in sickle cell disease: incidence and risk factors.	British journal of haematology 2021, Online ahead of print
Intravenous fluid therapy (IV-FT) is routinely used in the treatment of vaso-occlusive crises (VOCs), as dehydration possibly promotes and sustains erythrocyte sickling. Patients with sickle cell disease (SCD) are at risk of developing diastolic dysfunction and fluid overload due to IV-FT. However, data on the adverse effects of IV-FT for VOC is sparse. We aimed to evaluate the incidence and risk factors of fluid overload due to IV-FT in patients with SCD. Consecutive hospitalisations for VOC treated with IV-FT between September 2016 and September 2018 were retrospectively analysed. The median (interquartile range) age was 25·0 (18·3-33·8) years and 65% had a severe genotype (HbSS/HbSβ -thal). Fluid overload occurred in 21% of 100 patients. Hospital stay was longer in patients with fluid overload (6·0 vs. 4·0 days, P = 0·037). A positive history of fluid overload (P = 0·017), lactate dehydrogenase level (P = 0·011), and top-up transfusion during admission (P = 0·005) were independently associated with fluid overload occurrence. IV-FT was not reduced in 86% of patients despite a previous history of fluid overload. Fluid overload is frequently encountered during IV-FT for VOC. IV-FT is often not adjusted despite a positive history of fluid overload or when top-up transfusion is indicated, emphasising the need for more awareness of this complication and a personalised approach.
Gaab C, Adolph JE, Tippelt S, Mikasch R, Obrecht D, Mynarek M, Rutkowski S, Pfister SM, Milde T, Witt O, Bison B, Warmuth-Metz M, Kortmann RD, Dietzsch S, Pietsch T, Timmermann B, Sträter R, Bode U, Faldum A, Kwiecien R, Fleischhack G	Local and Systemic Therapy of Recurrent Medulloblastomas in Children and Adolescents: Results of the P-HIT-REZ 2005 Study.	Cancers 2022, 14
Recurrent medulloblastomas are associated with survival rates <10%. Adequate multimodal therapy is being discussed as having a major impact on survival. In this study, 93 patients with recurrent medulloblastoma treated in the German P-HIT-REZ 2005 Study were analyzed for survival (PFS, OS) dependent on patient, disease, and treatment characteristics. The median age at the first recurrence was 10.1 years (IQR: 6.9-16.1). Median PFS and OS, at first recurrence, were 7.9 months (CI: 5.7-10.0) and 18.5 months (CI: 13.6-23.5), respectively. Early relapses/progressions (<18 months, = 30/93) found mainly in molecular subgroup 3 were associated with markedly worse median PFS (HR: 2.34) and OS (HR: 3.26) in regression analyses. A significant survival advantage was found for the use of volume-reducing surgery as well as radiotherapy. Intravenous chemotherapy with carboplatin and etoposide (ivCHT, = 28/93) showed improved PFS and OS data and the best objective response rate (ORR) was 66.7% compared to oral temozolomide (oCHT, = 47/93) which was 34.8%. Intraventricular ( = 43) as well as high-dose chemotherapy ( = 17) at first relapse was not related to a significant survival benefit. Although the results are limited due to a non-randomized study design, they may serve as a basis for future treatment decisions in order to improve the patients' survival.
Gadner H, Heitger A, Grois N, Gatterer-Menz I, Ladisch S	Treatment strategy for disseminated Langerhans cell histiocytosis. DAL HX-83 Study Group.	Med Pediatr Oncol 1994, 23: 72
Gadner H, Ladisch S, Arico M, Broadbent V, Jakobson A, Komp D, Nicholson S	VP-16 and the treatment of histiocytosis.	Eur J Pediatr 1994, 153: 389
Gadner H	Etoposide in Langerhans cell histiocytosis.	Pediatr Hematol Oncol 1996, 13: 309
Gadner H	Therapie von Leukämien, Lymphomen, Soliden Tumoren, Spezielle Therapiemodalitäten, Regionale Chemotherapie, Notfälle.	Langerhans-Zell-Histiozytose in Kompendium Internistische Onkologie 1999, 2294
Gadner H	Langerhans' cell histiocytosis - still an unsolved problem editorial.	Pediatr Hematol Oncol 1999, 16: 489
Gadner H, Grois N, Arico M, Broadbent V, Ceci A, Jakobson A, Komp D, Michaelis J, Nicholson S, Potschger U, Pritchard J, Ladisch S	A randomized trial of treatment for multisystem Langerhans' cell histiocytosis.	J Pediatr 2001, 138: 728
Gadner H, Grois N, Arico M, Broadbent V, Ceci A, Jakobson A, Komp D, Michaelis J, Nicholson S, Pötschger U, Pritchard J, Ladisch S, Histiocyte Society	A randomized trial of treatment for multisystem Langerhans' cell histiocytosis.	The Journal of pediatrics 2001, 138: 728
OBJECTIVE: To compare 2 active agents, vinblastine and etoposide, in the treatment of multisystem Langerhans' cell histiocytosis (LCH) in an international randomized study. STUDY DESIGN: One hundred forty-three untreated patients were randomly assigned to receive 24 weeks of vinblastine (6 mg/m(2), given intravenously every week) or etoposide (150 mg/m(2)/d, given intravenously for 3 days every 3 weeks), and a single initial dose of corticosteroids. RESULTS: Vinblastine and etoposide were equivalent (P > or = .2) in all respects: response at week 6 (57% and 49%); response at the last evaluation (58% and 69%); toxicity (47% and 58%); and probability of survival (76% and 83%) [corrected], of disease reactivation (61% and 55%), and of developing permanent consequences (39% and 51%) including diabetes insipidus (22% and 23%). LCH reactivations were usually mild, as was toxicity. All children > or = 2 years old without risk organ involvement (liver, lungs, hematopoietic system, or spleen) survived. With such involvement, lack of rapid (within 6 weeks) response was identified as a new prognostic indicator, predicting a high (66%) mortality rate. CONCLUSIONS: Vinblastine and etoposide, with one dose of corticosteroids, are equally effective treatments for multisystem LCH, but patients who do not respond within 6 weeks are at increased risk for treatment failure and may require different therapy.
Gadner H, Haas O, Masera G, Pui C, Schrappe M	Ponte di Legno' Working Group--report on the Fifth International Childhood Acute Lymphoblastic Leukemia Workshop.	Leukemia 2003, 17: 798
Gadner H, Gaedicke G, Niemeyer CH, Ritter J (Hrsg)	Pädiatrische Hämatologie und Onkologie.	Springer-Verlag 2006
Gadner H, Minkov M, Grois N, Pötschger U, Thiem E, Aricò M, Astigarraga I, Braier J, Donadieu J, Henter JI, Janka-Schaub G, McClain KL, Weitzman S, Windebank K, Ladisch S	Therapy prolongation improves outcome in multi-system Langerhans cell histiocytosis.	Blood 2013, Epub ahead of print
LCH-III tested risk adjusted, intensified, longer treatment for multisystem Langerhans cell histiocytosis, for which optimal therapy has been elusive. Stratified by risk organ involvement [high (RO+) or low (RO-) risk groups], >400 patients were randomized. RO+ patients received 1-2 six-week courses of vinblastine+prednisone (Arm A) or vinblastine+prednisone+methotrexate (Arm B). Response triggered milder continuation therapy with the same combinations, plus 6-mercaptopurine, for 12 months total treatment. 6/12 week response rates (mean 71%) and five-year survival (84%) and reactivation rates (27%) were similar in both arms. Notably, historical comparisons revealed survival superior to that of identically stratified RO+ patients treated for 6 months in predecessor trials LCH-I (62%) or LCH-II (69%, p<0.001), and lower 5-year reactivation rates than in LCH-I (55%) or LCH-II (44%, p<0.001). RO- patients received vinblastine+prednisone throughout. Response by six weeks triggered randomization to 6 or 12 months total treatment. Significantly lower 5-year reactivation rates characterized the 12-month Arm D (37%), compared to 6-month Arm C (54%, p=0.03) or to 6 month schedules in LCH-I (52%) and LCH-II (48%, p<0.001). Thus, prolonging treatment decreased RO- patient reactivations in LCH-III, and while methotrexate added no benefit, RO+ patient survival and reactivation rates have substantially improved in the three sequential trials. (Trial No. NCT00276757 www.ClinicalTrials.gov).
Gajjar A, Sanford RA, Heideman R, Jenkins JJ, Walter A, Li Y, Langston JW, Muhlbauer M, Boyett JM, Kun LE	Low-grade astrocytoma: a decade of experience at St. Jude Children's Research Hospital.	Journal of clinical oncology : official journal of the American Society of Clinical Oncology 1997, 15: 2792
To evaluate the impact of primary tumor site, age at diagnosis, extent of resection, and histology on progression-free survival (PFS) in pediatric low-grade astrocytoma.
Gajjar A, Kühl J, Epelman S, Bailey C, Allen J	Chemotherapy of medulloblastoma.	Childs Nerv Syst 1999, 15: 554
Gallie BL, Dunn JM, Chan HS, Hamel PA, Phillips RA	The genetics of retinoblastoma. Relevance to the patient.	Pediatric clinics of North America 1991, 38: 299
The understanding of the molecular biology of human cancer has advanced rapidly in the last decade, in part due to discoveries in the rare, pediatric ocular tumor, retinoblastoma. RB studies have led to recognition of a class of human genes, the tumor suppressor genes, that are critical in the initiation and progression of the malignant process. Mutations in the RB1 gene initiate RB and other specific tumors. They may also contribute to progressive stages of many other malignancies. The protein product of RB1 (p110RB1) is a basic regulator of the cell cycle. In the absence of normal protein, the cell proceeds to the next cell division without the potential to become quiescent. Understanding the genetics of RB has benefited the patients, as the precise identification of the RB1 mutations in families has led to accurate prediction of individuals at risk for RB tumors. It seems unlikely, in the foreseeable future, that direct genetic manipulation of mutant RB1 genes will play a role in therapy, but complete understanding of the function of p110RB1 may eventually allow exploitation of its powerful antiproliferative effect. Other molecular genetic events in addition to RB1 mutations are documented in RB tumors, and may play a critical role in the full malignant phenotype. The oncogene, N-myc, is amplified in some RB tumors and is expressed in normal fetal retina. The cytogenetic abnormality, i(6p), is almost unique to RB tumors. The molecular and tissue-specific roles of these abnormalities are not yet known. Many RB tumors also acquire excessive expression of the cell surface membrane glycoprotein, p170, linked to multidrug resistance, whether or not the RB tumor has been exposed to chemotherapy. We anticipate that ways to avoid or counteract the drug resistance of excessive p170 expression will be developed for other pediatric tumors and eventually will be applied to chemotherapy for RB patients.
Galimi F, Noll M, Kanazawa Y, Lax T, Chen C, Grompe M, Verma IM	Gene therapy of Fanconi anemia: preclinical efficacy using lentiviral vectors.	Blood 2002, 100: 2732
Fanconi anemia (FA) is an inherited cancer susceptibility syndrome caused by mutations in a DNA repair pathway including at least 6 genes (FANCA, FANCC, FANCD2, FANCE, FANCF, and FANCG). The clinical course of the disease is dominated by progressive, life-threatening bone marrow failure and high incidence of acute myelogenous leukemia and solid tumors. Allogeneic bone marrow transplantation (BMT) is a therapeutic option but requires HLA-matched donors. Gene therapy holds great promise for FA, but previous attempts to use retroviral vectors in humans have proven ineffective given the impaired proliferation potential of human FA hematopoietic progenitors (HPCs). In this work, we show that using lentiviral vectors efficient genetic correction can be achieved in quiescent hematopoietic progenitors from Fanca(-/-) and Fancc(-/-) mice. Long-term repopulating HPCs were transduced by a single exposure of unfractionated bone marrow mononuclear cells to lentivectors carrying the normal gene. Notably, no cell purification or cytokine prestimulation was necessary. Resistance to DNA- damaging agents was fully restored by lentiviral transduction, allowing for in vivo selection of the corrected cells with nonablative doses of cyclophosphamide. This study strongly supports the use of lentiviral vectors for FA gene therapy in humans.
Ganz T, Nemeth E	Iron sequestration and anemia of inflammation.	Semin hematol 2009, 46: 387
Anemia of chronic disease, also called anemia of inflammation, is characterized by hypoferremia due to iron sequestration that eventually results in iron-restricted erythropoiesis. During the last decade, the molecular mechanisms of iron sequestration have been found to center on cytokine-stimulated overproduction of the iron-regulatory hormone hepcidin. The inflammatory cytokine interleukin-6 (IL-6) is a particularly prominent inducer of hepcidin, but other cytokines are likely to contribute as well. Hepcidin excess causes the endocytosis and proteolysis of the sole known cellular iron exporter, ferroportin, trapping iron in macrophages and iron-absorbing enterocytes. The supply of iron to hemoglobin synthesis becomes limiting, eventually resulting in anemia. Depending on the details of the underlying disease, other inflammation-related mechanisms may also contribute to anemia.
Ganz T	Hepcidin and iron regulation, 10 years later.	Blood 2011, 117: 4425
Under evolutionary pressure to counter the toxicity of iron and to maintain adequate iron supply for hemoglobin synthesis and essential metabolic functions, humans and other vertebrates have effective mechanisms to conserve iron and to regulate its concentration, storage, and distribution in tissues. The iron-regulatory hormone hepcidin, first described 10 years ago, and its receptor and iron channel ferroportin control the dietary absorption, storage, and tissue distribution of iron. Hepcidin causes ferroportin internalization and degradation, thereby decreasing iron transfer into blood plasma from the duodenum, from macrophages involved in recycling senescent erythrocytes, and from iron-storing hepatocytes. Hepcidin is feedback regulated by iron concentrations in plasma and the liver and by erythropoietic demand for iron. Genetic malfunctions affecting the hepcidin-ferroportin axis are a main cause of iron overload disorders but can also cause iron-restricted anemias. Modulation of hepcidin and ferroportin expression during infection and inflammation couples iron metabolism to host defense and decreases iron availability to invading pathogens. This response also restricts the iron supply to erythropoietic precursors and may cause or contribute to the anemia associated with infections and inflammatory disorders.
Ganz T	Iron and infection.	International journal of hematology 2018, 107: 7
Iron is an essential trace metal for nearly all infectious microorganisms, and host defense mechanisms target this dependence to deprive microbes of iron. This review highlights mechanisms that are activated during infections to restrict iron on mucosal surfaces, in plasma and extracellular fluid, and within macrophages. Iron overload disorders, such as hereditary hemochromatosis or β-thalassemia, interfere with iron-restrictive host responses, and thereby cause increased susceptibility to infections with microbes that can exploit this vulnerability. Anemia of inflammation (formerly known as anemia of chronic diseases) is an "off-target" effect of host defense wherein inflammatory cytokines shorten erythrocyte lifespan by activating macrophages, prioritize leukocyte production in the marrow, and induce hepcidin to increase plasma transferrin saturation and the concentration of non-transferrin-bound iron.
Garre M, El-Hossainy M, Fondelli P, Göbel U, Brisigotti M, Donati P, Nantron M, Ravegnani M, Garaventa A, De Bernardi B	Is chemotherapy effective therapy for intracranial immature teratoma?	Cancer 1996, 77: 977
Garde S, Knaup P, Herold R	Remodeling of Legacy Systems in Health Care using UML.	Stud Health Technol Inform 2002, 90: 478
Garde S, Baumgarten B, Basu O, Graf N, Haux R, Herold R, Kutscha U, Schilling F, Selle B, Spiess C, Wetter T, Knaup P	A Meta-Model of Chemotherapy Planning in the Multi-Hospital / Multi-Trial-Center-Environment of Pediatric Oncology.	Methods of Information in Medicine 2004, 43: 171
Garbe E, Andersohn F, Bronder E, Klimpel A, Thomae M, Schrezenmeier H, Hildebrandt M, Späth-Schwalbe E, Grüneisen A, Mayer B, Salama A, Kurtal H	Drug induced immune haemolytic anaemia in the Berlin Case-Control Surveillance Study.	British journal of haematology 2011, 154: 644
Drug-induced immune haemolytic anaemia is a rare but serious condition. This study investigated the possibility of drug aetiology of immune haemolytic anaemia (IHA) in 134 patients with new onset of IHA who were identified in the Berlin Case-Control Surveillance Study between 2000 and 2009. Single drugs related to IHA in three or more patients and assessed more than once as a certain or probable cause of IHA in a standardized causality assessment included diclofenac, fludarabine, oxaliplatin, ceftriaxone and piperacillin. In a case-control study including all 124 IHA cases developed in outpatient care and 731 controls, significantly increased odds ratios (OR) were observed for beta-lactam antibiotics (OR=8·8; 95% confidence interval [CI] 3·2-25·2), cotrimoxazole (OR=6·5; CI 1·1-37·9), ciprofloxacin (OR=6·9, CI 1·3-38·5), fludarabine (OR=22·2; CI: 2·8-454·5) and lorazepam (OR=5·3; CI: 1·2-21·2). Excluding new onset cases with a chronic IHA disease course, an increased risk became also apparent for diclofenac with an OR of 3·1 (CI 1·3-7·0). This is the first case-control study investigating drugs as risk factors for IHA. It corroborates an increased risk for several drugs that have been implicated as a cause of IHA in the standardized causality assessment of individual cases.
Garcia-Puig M, Fons-Estupina MC, Rives-Sola S, Berrueco-Moreno R, Cruz-Martinez O, Campistol J	[Neurotoxicity due to methotrexate in paediatric patients. Description of the clinical symptoms and neuroimaging findings].	Revista de neurologia 2012 Jun 16; 54: 712
Garçon L, Ge J, Manjunath SH, Mills JA, Apicella M, Parikh S, Sullivan LM, Podsakoff GM, Gadue P, French DL, Mason PJ, Bessler M, Weiss MJ	Ribosomal and hematopoietic defects in induced pluripotent stem cells derived from Diamond Blackfan anemia patients.	Blood 2013, 122: 912
Diamond Blackfan anemia (DBA) is a congenital disorder with erythroid (Ery) hypoplasia and tissue morphogenic abnormalities. Most DBA cases are caused by heterozygous null mutations in genes encoding ribosomal proteins. Understanding how haploinsufficiency of these ubiquitous proteins causes DBA is hampered by limited availability of tissues from affected patients. We generated induced pluripotent stem cells (iPSCs) from fibroblasts of DBA patients carrying mutations in RPS19 and RPL5. Compared with controls, DBA fibroblasts formed iPSCs inefficiently, although we obtained 1 stable clone from each fibroblast line. RPS19-mutated iPSCs exhibited defects in 40S (small) ribosomal subunit assembly and production of 18S ribosomal RNA (rRNA). Upon induced differentiation, the mutant clone exhibited globally impaired hematopoiesis, with the Ery lineage affected most profoundly. RPL5-mutated iPSCs exhibited defective 60S (large) ribosomal subunit assembly, accumulation of 12S pre-rRNA, and impaired erythropoiesis. In both mutant iPSC lines, genetic correction of ribosomal protein deficiency via complementary DNA transfer into the
Gaspar N, Hawkins DS, Dirksen U, Lewis IJ, Ferrari S, Le Deley MC, Kovar H, Grimer R, Whelan J, Claude L, Delattre O, Paulussen M, Picci P, Sundby Hall K, van den Berg H, Ladenstein R, Michon J, Hjorth L, Judson I, Luksch R, Bernstein ML, Marec-Bérard P, Brennan B, Craft AW, Womer RB, Jürgens H, Oberlin O	Ewing Sarcoma: Current Management and Future Approaches Through Collaboration.	Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2015 Sep 20; 33: 3036
Gastberger K, Fincke VE, Mucha M, Siebert R, Hasselblatt M, Frühwald MC	Current Molecular and Clinical Landscape of ATRT - The Link to Future Therapies.	Cancer management and research 2023, 15: 1369
Gatta G, Capocaccia R, Stiller C, Kaatsch P, Berrino F, Terenziani M, EUROCARE Working Group	Childhood cancer survival trends in Europe: a EUROCARE Working Group study.	Journal of clinical oncology 2005, 23: 3742
PURPOSE: EUROCARE collected data from population-based cancer registries in 20 European countries. We used this data to compare childhood cancer survival time trends in Europe. PATIENTS AND METHODS: Survival in 44,129 children diagnosed under the age of 15 years during 1983 to 1994 was analyzed. Sex- and age-adjusted 5-year survival trends for 10 common cancers and for all cancers combined were estimated for five regions (West Germany, the United Kingdom, Eastern Europe, Nordic countries, and West and South Europe) and Europe as a whole. Europe-wide trends for 14 rare cancers were estimated. RESULTS: For all cancers combined, 5-year survival increased from 65% for diagnoses in 1983 to 1985 to 75% in 1992 to 1994. Survival improved for all individual cancers except melanoma, osteosarcoma, and thyroid carcinoma; although for retinoblastoma, chondrosarcoma, and fibrosarcoma, improvements were not significant. The most marked improvements (50% to 66%) occurred in Eastern Europe. For common cancers, the greatest improvements were for leukemia and lymphomas, with risk of dying reducing significantly by 5% to 6% per year. Survival for CNS tumors improved significantly from 57% to 65%, with risk reducing by 3% per year. Risk reduced by 4% per year for neuroblastoma and 3% per year for Wilms' tumor and rhabdomyosarcoma. The survival gap between regions reduced over the period, particularly for acute nonlymphocytic leukemia, CNS tumors, and rhabdomyosarcoma. For rare Burkitt's lymphoma, hepatoblastoma, gonadal germ cell tumors, and nasopharyngeal carcinoma, risk reductions were at least 10% per year. CONCLUSION: These gratifying improvements in survival can often be plausibly related to advances in treatment. The prevalence of European adults with a history of childhood cancer will inevitably increase.
Gauß G, Beller R, Boos J, Däggelmann J, Stalf H, Wiskemann J, Götte M	Adverse Events During Supervised Exercise Interventions in Pediatric Oncology-A Nationwide Survey.	Frontiers in pediatrics 2021, 9: 682496
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Gawade PL, Hudson MM, Kaste SC, Neglia JP, Constine LS, Robison LL, Ness KK	A systematic review of dental late effects in survivors of childhood cancer.	Pediatric blood & cancer 2014, 61: 407
Survivors of childhood cancer are at risk for dental late effects. This systematic review summarizes associations between treatment exposures and dental late effects among survivors of childhood cancer. We included investigations with at least 20 study participants conducted for 2 or more years after completion of childhood, adolescent, or young adult cancer therapy. This review suggests both independent and additive effects of radiotherapy and chemotherapy on dental complications, and identifies vulnerable groups with specific host and treatment characteristics. This summary provides information that will assist clinicians to prevent, detect, and facilitate early intervention for dental late effects.
Gazda H, Lipton JM, Willig TN, Ball S, Niemeyer CM, Tchernia G, Mohandas N, Daly MJ, Ploszynska A, Orfali KA, Vlachos A, Glader BE, Rokicka-Milewska R, Ohara A, Baker D, Pospisilova D, Webber A, Viskochil DH, Nathan DG, Beggs AH, Sieff CA	Evidence for linkage of familial Diamond-Blackfan anemia to chromosome 8p23. 3-p22 and for non-19q non-8p disease.	Blood 2001, 97: 2145
Diamond-Blackfan anemia (DBA) is a rare congenital hypoplastic anemia that usually presents early in infancy and is inherited in 10% to 20% of cases. Linkage analysis has shown that DBA in many of both dominant and recessive DBA families mapped to chromosome 19q13.2 leading to the cloning of a gene on chromosome 19q13.2 that encodes a ribosomal protein, RPS19. However, subsequently, mutations of the RPS19 gene have only been identified in 25% of all patients with DBA. This study analyzed 14 multiplex DBA families, 9 of which had 19q13.2 haplotypes inconsistent with 19q linkage. A genome-wide search for linked loci suggested the presence of a second DBA locus in a 26.4-centimorgan (cM) interval on human chromosome 8p. Subsequently, 24 additional DBA families were ascertained and all 38 families were analyzed with additional polymorphic markers on chromosome 8p. In total, 18 of 38 families were consistent with linkage to chromosome 8p with a maximal LOD score with heterogeneity of 3.55 at D8S277 assuming 90% penetrance. The results indicate the existence of a second DBA gene in the 26.4-cM telomeric region of human chromosome 8p23.3-p22, most likely within an 8.1-cM interval flanked by D8S518 and D8S1825. Seven families were inconsistent with linkage to 8p or 19q and did not reveal mutations in the RPS19 gene, suggesting further genetic heterogeneity. (Blood. 2001;97:2145-2150)
Gazda, HT, Zhong R, Long L, Niewiadomska E, Lipton, JM, Ploszynska A, Zaucha, JM, Vlachos A, Atsidaftos E, Viskochil, DH, Niemeyer, CM, Meerpohl, JJ, Rokicka-Milewska R, Pospisilova D, Wiktor-Jedrzejczak W, Nathan, DG, Beggs, AH, Sieff, CA	RNA and protein evidence for haplo-insufficiency in Diamond-Blackfan anaemia patients with RPS19 mutations.	Br J Haematol 2004, 127: 105
The genetic basis of Diamond-Blackfan anaemia (DBA), a congenital erythroid hypoplasia that shows marked clinical heterogeneity, remains obscure. However, the fact that nearly one-quarter of patients harbour a variety of mutations in RPS19, a ribosomal protein gene, provides an opportunity to examine whether haplo-insufficiency of RPS19 protein can be demonstrated in certain cases. To that end, we identified 19 of 81 DBA index cases, both familial and sporadic, with RPS19 mutations. We found 14 distinct insertions, deletions, missense, nonsense and splice site mutations in the 19 probands, and studied mutations in 10 patients at the RNA level and in three patients at the protein level. Characterization of the mutations in 10 probands, including six with novel insertions, nonsense and splice site mutations, showed that the abnormal transcript was detectable in nine cases. The RPS19 mRNA and protein in CD34+ bone marrow cells identified haplo-insufficiency in three cases predicted to have one functional allele. Our data support the notion that, in addition to rare DBA patients with the deletion of one allele, the disease in certain other RPS19 mutant patients is because of RPS19 protein haplo-insufficiency.
Gazda, HT, Grabowska A, Merida-Long, LB, Latawiec E, Schneider, HE, Lipton, JM, Vlachos A, Atsidaftos E, Ball, SE, Orfali, KA, Niewiadomska E, Da Costa L, Tchernia G, Niemeyer C, Meerpohl, JJ, Stahl J, Schratt G, Glader B, Backer K, Wong C, Nathan, DG, Beggs, AH, Sieff, CA	Ribosomal protein S24 gene is mutated in Diamond-Blackfan anemia.	Am.J Hum.Genet 2006, 79: 1110-8. Epub 2006 Nov 2.
Diamond-Blackfan anemia (DBA) is a rare congenital red-cell aplasia characterized by anemia, bone-marrow erythroblastopenia, and congenital anomalies and is associated with heterozygous mutations in the ribosomal protein (RP) S19 gene (RPS19) in approximately 25% of probands. We report identification of de novo nonsense and splice-site mutations in another RP, RPS24 (encoded by RPS24 [10q22-q23]) in approximately 2% of RPS19 mutation-negative probands. This finding strongly suggests that DBA is a disorder of ribosome synthesis and that mutations in other RP or associated genes that lead to disrupted ribosomal biogenesis and/or function may also cause DBA.
Gemeinsamer Bundesausschuss	Richtlinien zur Kinderonkologie.	Stand 01/2023 aufgerufen am 6.12.2023
Gebert C, Brinkschmidt C, Bielack S, Bernhardt T, Jürgens H, Böcker W, Winkelmann W, Bürger H, Gosheger, G	The potential of comparative genomic hybridization as a tool in the differential diagnosis of matrix-producing bone lesions.	Int J Surg Pathol 2006, 14: 187
Matrix-producing bone lesions consist of a wide variety of benign and malignant conditions. With respect to morphology, an overlap exists between benign and malignant bone tumors that causes difficulties in the final determination of the tumor. This study was conducted to show the potential of comparative genomic hybridization as a tool in the differential diagnosis of matrix-producing bone lesions. Thirty benign bone tumors were evaluated by conventional comparative genomic hybridization. To test its diagnostic reliability, 5 additional cases were analyzed, all with differential diagnostic difficulties related to morphology and radiology. All were ultimately diagnosed as malignant sarcomas, and unbalanced alterations were detected. In contrast benign tumors or tumor-like lesions did not reveal any chromosomal alterations. Comparative genomic hybridization is a useful adjunct in the complicated differential diagnostic algorithms of matrix-producing bone tumors.
Gebauer J, Baust K, Bardi E, Grabow D, Stein A, van der Pal HJ, Calaminus G, Langer T	Guidelines for Long-Term Follow-Up after Childhood Cancer: Practical Implications for the Daily Work.	Oncology research and treatment 2020, 43: 61
Many childhood cancer survivors develop treatment-associated late effects emerging years or even decades after the end of treatment. Evidence-based guidelines recommend risk-adapted screening, facilitating early diagnosis and management of these sequelae. Long-term follow-up (LTFU) in specialized late effects clinics is devised to implement screening recommendations in the care of childhood cancer survivors.
Gehring M, Berthold F, Schwab M, Amler L	Genetic stability of microsatellites in human neuroblastomas.	J Clin Oncol 1994, 4: 1043
Gehring M, Berthold F, Edler L, Schwab M, Amler L	The 1p deletion is not a reliable marker for the prognosis of patients with neuroblastoma.	Cancer Res 1995, 55: 5366
George JN, Shattil SJ	The clinical importance of acquired abnormalities of platelet function.	The New England journal of medicine 1991 Jan 3; 324: 27
Geoerger B, Hero B, Harms D, Grebe J, Scheidhauer K, Berthold F	Metabolic activity and clinical features of primary ganglioneuromas.	Cancer 2001, 91: 1905
George JN, Vesely SK	Immune thrombocytopenic purpura--let the treatment fit the patient.	The New England journal of medicine 2003, 349: 903
George JN	Children with ITP: Looking beyond the platelet count.	Pediatric blood & cancer 2012, 58: 323
Georgi TW, Kluge R, Kurch L, Chavdarova L, Hasenclever D, Stoevesandt D, Pelz T, Landman-Parker J, Wallace WH, Karlen J, Fernández-Teijeiro A, Cepelova M, Fosså A, Balwierz W, Attarbaschi A, Ammann RA, Pears J, Hraskova A, Uyttebroeck A, Beishuizen A, Dieckmann K, Leblanc T, Daw S, Baumann J, Körholz D, Sabri O, Mauz-Körholz C	18F-FDG PET Response of Skeletal (Bone Marrow and Bone) Involvement After Induction Chemotherapy in Pediatric Hodgkin Lymphoma: Are Specific Response Criteria Required?	Journal of nuclear medicine : official publication, Society of Nuclear Medicine 2018, 59: 1524
To determine whether the current F-FDG PET response criterion for skeletal involvement in Hodgkin lymphoma (HL) is suitable, we performed a systematic evaluation of the different types of skeletal involvement and their response on PET after 2 cycles of chemotherapy (PET-2). A secondary objective was to observe the influence of the initial uptake intensity (measured as qPET) and initial metabolic tumor volume (MTV) of skeletal lesions on the PET-2 response. The initial PET scans of 1,068 pediatric HL patients from the EuroNet-PHL-C1 trial were evaluated for skeletal involvement by central review. Three types of skeletal lesions were distinguished: PET-only lesions (those detected on PET only), bone marrow (BM) lesions (as confirmed by MRI or BM biopsy), and bone lesions. qPET and MTV were calculated for each skeletal lesion. All PET-2 scans were assessed for residual tumor activity. The rates of complete metabolic response for skeletal and nodal involvement on PET-2 were compared. Of the 1,068 patients, 139 (13%) showed skeletal involvement (44 PET-only, 32 BM, and 63 bone). Of the 139 patients with skeletal involvement, 101 (73%) became PET-2-negative in the skeleton and 94 (68%) became PET-2-negative in the lymph nodes. The highest number of PET-2-negative scans in the skeleton was 42 (95%) in the 44 PET-only patients, followed by 22 skeletal lesions (69%) in the 32 BM patients and 37 (59%) in the 63 bone patients. Lesions that became PET-2-negative showed a lower initial median qPET (2.74) and MTV (2 cm) than lesions that remained PET-2-positive (3.84 and 7 cm, respectively). In this study with pediatric HL patients, the complete response rate for skeletal involvement on PET-2 was similar to that for nodal involvement. Bone flare seemed to be irrelevant. Overall, the current skeletal PET response criterion-comparison with the local skeletal background-is well suited. The initial qPET and MTV of skeletal lesions were predictive of the PET-2 result. Higher values for both parameters were associated with a worse PET-2 response.
Gerhardt T, Schmahl G, Flotho C, Rath A, Niemeyer C	Expression of the Evi-1 gene in haemopoietic cells of children with juvenile myelomonocytic leukaemia and normal donors.	Br J Haematol 1997, 99: 882
Gerres L, Brämswig J, Schlegel W, Jürgens H, Schellong G	The effects of etoposide on testicular function in boys treated for Hodgkin's disease.	Cancer 1998, 83: 2217
Gerth HU, Rompel A, Krebs B, Boos J, Lanvers-Kaminsky C	Cytotoxic effects of novel polyoxotungstates and a platinum compound on human cancer cell lines.	Anti-cancer drugs 2005, 16: 101
The cytotoxicity of a new platinum compound Pt1 [2,9-dimethyl-4,7-diphenyl-1,10-phenanthrolinedichloroplatin(II)] and six polyoxometalates (POM1-6) on two neuroblastoma cell lines (SHEP-SF and KCN) and an Ewing's Sarcoma cell line (CADO-ES-1) was studied. Cisplatin [cis-diamminedichloroplatinum(II)] and carboplatin [cis-diammine(cyclobutanedicarboxylato)platinum(II)] were used as reference agents. Using MTT tests, the cytotoxicity (LD50: lethal doses 50%) of the compounds were measured at different concentrations. After 72 h exposure, the LD50 data for the platinum-containing substances ranged between 4.47 x 10(-6) and 1.91 x 10(-4) M. The SHEP-SF cell line displayed the highest sensitivity to cisplatin. The novel platinum agent Pt1 had a similar cytotoxic effect to the reference agent cisplatin. Both cisplatin and Pt1 were more cytotoxic than carboplatin. The POMs reduced cell viability compared to untreated cells at concentrations between 8.4 x 10(-7) and 3.47 x 10(-5) M. POM1 ([(CH3)4N]2Na6.5(NH4)2[SnII1.5(WO2(OH))0.5(WO2)2(SbW9O33)2] x 32H2O) was the most effective polyoxoanion with a mean LD50 value of 8.83 x 10(-6) M in the three cell lines tested. With CADO-ES-1 and KCN cells, POM1 was found to be more effective than the platinum compounds cisplatin, carboplatin and Pt1.
Gerth HU, Juergens KU, Dirksen U, Gerss J, Schober O, Franzius C	Significant benefit of multimodal imaging: PET/CT compared with PET alone in staging and follow-up of patients with Ewing tumors.	Journal of nuclear medicine : official publication, Society of Nuclear Medicine 2007, 48: 1932
Germeshausen M, Skokowa J, Ballmaier M, Zeidler C, Welte K	G-CSF receptor mutations in patients with congenital neutropenia.	Current opinion in hematology 2008, 15: 332
In this review, we summarize our current knowledge on the acquisition of granulocyte-colony stimulating factor receptor (G-CSFR) gene (CSF3R) mutations in patients with congenital neutropenia and their role in leukemogenesis. Congenital neutropenia is a heterogeneous disorder of hematopoiesis characterized by a maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10/l.
Gerrard M, Cairo MS, Weston C, Auperin A, Pinkerton R, Lambilliote A, Sposto R, McCarthy K, Lacombe MJ, Perkins SL, Patte C, FAB LMB96 International Study Committee	Excellent survival following two courses of COPAD chemotherapy in children and adolescents with resected localized B-cell non-Hodgkin's lymphoma: results of the FAB/LMB 96 international study.	British journal of haematology 2008, 141: 840
High cure rates are possible in children with localized mature B-cell lymphoma (B NHL) using a variety of chemotherapeutic strategies. To reduce late sequelae, the duration and intensity of chemotherapy has been progressively reduced. The Lymphome Malins de Burkitt (LMB) 89 study reported long-term survival in almost all children with localized resected disease treated with two courses of COPAD (cyclophosphamide, vincristine, prednisolone and doxorubicin). This study was designed to confirm the effectiveness of this approach in a larger number of patients in a multinational co-operative study. The patient cohort was part of an international study (French-American-British LMB 96), which included all disease stages and involved three national groups. Patients in this part of the study had resected stage I or completely resected abdominal stage II disease. Following surgery, two courses of COPAD were given, without intrathecal (IT) chemotherapy. One hundred and thirty-two children were evaluable. Two of 264 (0.9%) courses were associated with grade IV toxicity (one stomatitis and one infection). With a median follow up of 50.5 months, the 4 year event-free survival is 98.3% and overall survival is 99.2%. Children with resected localized B-NHL can be cured with minimal toxicity following two courses of low intensity treatment without IT chemotherapy.
Germing U, Aul C, Niemeyer CM, Haas R, Bennett JM	Epidemiology, classification and prognosis of adults and children with myelodysplastic syndromes.	Annals of hematology 2008, 87: 691
Myelodysplastic syndromes (MDS) belong to the most frequent bone marrow diseases with a crude incidence of about 4 in 100,000 per year. The diagnosis of MDS still is mainly based on morphologic findings in blood and marrow. The new WHO classification system takes into account the medullary and peripheral blast count as well as the degree of dysplasia in the different cell lines. To correctly identify MDS types, cytogenetic evaluation is of importance, as the WHO classification introduced the entity MDS with del(5q), which is characterized by special morphologic and hematologic features. The separation of MDS from acute leukemias has been redefined using a cutoff value of 20% peripheral and/or medullary blasts. The International Prognostic Scoring System still is the gold standard in prognostication, but new items like transfusion need will be used more and more and have been incorporated into the WHO adapted Prognostic Scoring System. In childhood, MDS is uncommon, accounting for less than 5% of all hematopoietic neoplasms in patients less than 14 years of age. To accommodate for the characteristics of pediatric MDS, a simple classification scheme based on morphological features and conforming with the WHO suggestions was proposed. The dysplastic prodrome of acute myeloid leukemia in Down syndrome is classified within myeloid leukemia in Down syndrome and excluded from the population-based studies of MDS.
Gerr H, Zimmermann M, Schrappe M, Dworzak M, Ludwig WD, Bradtke J, Moericke A, Schabath R, Creutzig U, Reinhardt D	Acute leukaemias of ambiguous lineage in children: characterization, prognosis and therapy recommendations.	British journal of haematology 2010, 149: 84
Summary Acute leukaemias of ambiguous lineage (ALAL) represent a rare type of leukaemia, expressing both myeloid and lymphoid markers. This study retrospectively analyzed data from 92 children (biphenotypic n = 78, bilineal n = 6, lineage switch n = 8) with ALAL registered in the Berlin-Frankfürt-Münster (BFM) acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL) studies between 1998 and 2006 (2.4% of all cases with acute leukaemia). Our cohort of ALAL patients was characterized by comparatively high median age (8.9 years), high median white blood cell count (14.9 x 10(9)/l), as well as frequent hyperleucocytosis (18.5%) and central nervous system involvement (24.1%). The most frequent cytogenetic abnormalities were ETV6/RUNX1 fusion (16%) and trisomy 8 (14.6%). Complete remission rate was significantly lower than in ALL-BFM patients (91.8% vs. 99.1%, P < 0.001), but comparable to AML-BFM patients (87.9%). Event-free survival (EFS) and overall survival (OS) of ALAL patients were low, at 62 +/- 5%. 5-year probability of EFS was significantly worse than in ALL patients (80 +/- 1%, P < 0.001), but better than for AML patients (49 +/- 2%, P = 0.027). Our data suggest that an intensive therapy regimen including stem cell transplantation may be favourable for bilineal or lineage switch cases, whereas patients with ETV6/RUNX1 fusion, lymphoid morphology and patients with expression of cyCD22 and cyCD79a should be treated with an ALL-directed therapy.
Gerber A, Rossi R	Neonatologische Versorgung – Fallzahlregelung Einfluss auf Qualität und Finanzierung pädiatrischer Einrichtungen.	Monatsschr Kinderheilkd 2010 158: 356–363
Gerber NU, von Hoff K, von Bueren AO, Treulieb W, Warmuth-Metz M, Pietsch T, Soerensen N, Faldum A, Emser A, Schlegel PG, Deinlein F, Kortmann RD, Rutkowski S	Outcome of 11 children with ependymoblastoma treated within the prospective HIT-trials between 1991 and 2006.	J Neurooncol 2011, 102: 459
Ependymoblastoma is a rare malignant brain tumor of early childhood. Data on clinical behavior and optimal treatment strategies are scarce. We report on 11 consecutively treated children with centrally confirmed diagnosis of CNS ependymoblastoma, registered between February 1994 and October 2006 to the prospective GPOH-HIT multicenter brain tumor trials, and treated by multimodal regimens. Median age at diagnosis was 3.5 years (range, 1.8-5.6 years), and the median follow-up of survivors was 5.9 years (range, 2.2-12.7 years). Initial stage was M0 in 9, and M0/1 (no cerebrospinal fluid examination done) in 2 patients. Gross-total tumor resection was achieved in 7 patients, incomplete resection in 4 patients. Further primary therapy included chemotherapy in all patients, craniospinal radiotherapy in 5 patients and high-dose chemotherapy in 2 patients. Tumor response to chemotherapy was observed in 1 of 4 evaluable patients. Tumor progression occurred in 7 patients after a median time of 5.0 months (range, 2.5-19.2 months). Five-year progression-free survival was 36.4% (±14.5%), 5-year overall survival 30.3% (±15.9%). Of 4 survivors, 3 had gross-total tumor resection, and all were treated by either craniospinal radiotherapy and/or high-dose chemotherapy with autologous blood stem cell rescue. Prognosis of children with ependymoblastoma is poor, but sustained remissions have been achieved after multimodal treatment. Considerable diagnostic discrepancies between local and central pathologists underscore the importance of central review. Further studies are needed to improve survival of children with this rare malignant central nervous system tumor.
Gerber NU, von Hoff K, von Bueren AO, Treulieb W, Deinlein F, Benesch M, Zwiener I, Soerensen N, Warmuth-Metz M, Pietsch T, Mittler U, Kuehl J, Kortmann RD, Grotzer MA, Rutkowski S	A long duration of the prediagnostic symptomatic interval is not associated with an unfavourable prognosis in childhood medulloblastoma.	European journal of cancer 2011, [Epub ahead of print]
BACKGROUND: Due to the lacking specificity of symptoms making a correct diagnosis can be a challenge in children with medulloblastoma. This can lead to prediagnostic symptomatic intervals (PSIs) of several weeks to months. It is unknown whether the length of the PSI is associated with an inferior survival outcome in this population. METHODS: To study the association of PSI with disease stage at diagnosis, tumour control and survival in children with medulloblastoma, prospectively collected data on PSI, clinical, and biological features were analysed in 224 patients diagnosed at the age of 3-18years and treated within the prospective randomised multicentre trial HIT'91. RESULTS: Patients with lower-stage disease tended towards a longer median PSI than those with higher-stage disease (M0 stage, 2.0months; M1 stage, 2.0months; M2/M3 stage, 1month; p=0.094. M0/1 stage versus M2/3 stage; p=0.025). The patient group with the longest PSI had the best survival outcome (PSI ⩾4.0months: 10-year overall survival rate (OS), 71%; PSI <4.0months, 10-year OS, 61%; p=0.056). Age at diagnosis was positively correlated with PSI (p=0.027). No associations were found between PSI and sex histological subtype, presence of postoperative residual tumour, or c-myc and TrkC mRNA expression. CONCLUSION: Contrary to a common belief that a longer PSI may adversely affect prognosis, a longer PSI was associated with a trend towards lower metastatic stage and better survival probabilities. Nevertheless these findings do not obviate the importance of a timely diagnosis in paediatric patients with medulloblastoma.
Gerber NU, von Hoff K, Resch A, Ottensmeier H, Kwiecien R, Faldum A, Matuschek C, Hornung D, Bremer M, Benesch M, Pietsch T, Warmuth-Metz M, Kuehl J, Rutkowski S, Kortmann RD	Treatment of children with central nervous system primitive neuroectodermal tumors/pinealoblastomas in the prospective multicentric trial HIT 2000 using hyperfractionated radiation therapy followed by maintenance chemotherapy.	International journal of radiation oncology, biology, physics 2014, 89: 863
The prognosis for children with central nervous system primitive neuroectodermal tumor (CNS-PNET) or pinealoblastoma is still unsatisfactory. Here we report the results of patients between 4 and 21 years of age with nonmetastatic CNS-PNET or pinealoblastoma diagnosed from January 2001 to December 2005 and treated in the prospective GPOH-trial P-HIT 2000-AB4.
Gerber NU, Mynarek M, von Hoff K, Friedrich C, Resch A, Rutkowski S	Recent developments and current concepts in medulloblastoma.	Cancer treatment reviews 2014, 40: 356
Medulloblastoma is the most common malignant brain tumor of childhood. While prognosis has significantly improved in the last decades with multimodal therapy including surgery, radiotherapy, and chemotherapy, one third of patients still succumb to their disease. Further research is needed to find more efficient treatment strategies for prognostically unfavorable patient groups and to minimize long-term sequelae of tumor treatment. This review gives a summary of the current state of treatment concepts including an outlook on the near future. We describe recent advances in the understanding of molecular mechanisms, their potential impact on risk stratification in upcoming clinical trials, and perspectives for the clinical implementation of targeted therapies.
Gerstl L, Heinen F, Borggraefe I, Olivieri M, Kurnik K, Nicolai T, Reiter K, Berweck S, Schröder AS	Pädiatrischer Schlaganfall – ein kinderneurologischer Notfall. Klinik, Diagnostik und Therapie.	Monatsschr Kinderheilkd 2017, 5
Gerrand C, Bate J, Seddon B, Dirksen U, Randall RL, van de Sande M, O'Donnell P, Tuckett J, Peake D, Jeys L, Saifuddin A, Grainger M, Whelan J	Seeking international consensus on approaches to primary tumour treatment in Ewing sarcoma.	Clinical sarcoma research 2020, 10: 21
The local treatment of Ewing sarcoma of bone involves surgery, radiotherapy or both. The selection of treatment depends on the anatomical extent of the tumour, the effectiveness of the proposed treatment, its morbidity, and the expectation of cure. However, not only are there variations in the approach to local treatment between individual patients, but also between treatment centres and countries. Our aim was to explore variation in practice and develop consensus statements about local treatment.
Gessi M, von Bueren AO, Treszl A, Mühlen AZ, Hartmann W, Warmuth-Metz M, Rutkowski S, Pietsch T	MYCN amplification predicts poor outcome for patients with supratentorial primitive neuroectodermal tumors of the central nervous system.	Neuro-oncology 2014,
BackgroundPrimitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are a rare group of neoplasms occurring in the CNS that includes supratentorial CNS-PNETs, medulloepitheliomas, and ependymoblastomas. While ependymoblastomas frequently carry chromosome 19q13.41 amplification and show aggressive clinical behavior, the biological mechanisms and molecular alterations contributing to the pathogenesis of supratentorial CNS-PNETs remain poorly understood. Moreover, genetic alterations suitable for molecular risk stratification are undefined to date.MethodsIn order to identify possible molecular markers, we performed multiplex ligation-dependent probe amplification (MLPA) and molecular inversion probe (MIP) analysis on DNA samples of 25 supratentorial CNS-PNETs (median age, 5.35 years; range, 2.41-17.28 years). Tumors with ependymoblastic rosettes (ependymoblastoma/ETANTR) and LIN28A positivity were excluded.ResultsMLPA and MIP analysis revealed large losses of genomic material of chromosomes 3, 4, 5, and 13, while frequent gains affected chromosomes 1, 17, 19, 20, and 22. High copy number gains (amplifications) were found in particular at chromosomes 2p24.3 (MYCN, n = 6 cases) and 4q12 (n = 2 cases). Patients with tumors harboring 2p gain or MYCN amplification showed unfavorable overall survival (P = .003 and P = .001, respectively).These markers were independent of the presence of metastases, which was indeed a clinical factor associated with poor overall survival (P = .01) in this series.ConclusionsIn the era of the personalized neuro-oncology, the identification of these molecular prognostic markers associated with patient outcome may represent a significant step towards improved patient stratification and risk-adapted therapeutic strategies for patients suffering from supratentorial CNS-PNETs.
Gessi M, Capper D, Sahm F, Huang K, von Deimling A, Tippelt S, Fleischhack G, Scherbaum D, Alfer J, Juhnke BO, von Hoff K, Rutkowski S, Warmuth-Metz M, Chavez L, Pfister SM, Pietsch T, Jones DT, Sturm D	Evidence of H3 K27M mutations in posterior fossa ependymomas.	Acta neuropathologica 2016, 132: 635
Gessler M, Graf N	Less may be more for stage I epithelial Wilms tumors.	Cancer 2020, 126: 2762
No abstract available
Geyer JR, Finlay JL, Boyett JM, Wisoff J, Yates A, Mao L, Packer RJ	Survival of infants with malignant astrocytomas. A Report from the Childrens Cancer Group.	Cancer 1995, 75: 1045
Ghosh MC, Zhang DL, Ollivierre WH, Noguchi A, Springer DA, Linehan WM, Rouault TA	Therapeutic inhibition of HIF-2α reverses polycythemia and pulmonary hypertension in murine models of human diseases.	Blood 2021, 137: 2509
Polycythemia and pulmonary hypertension are 2 human diseases for which better therapies are needed. Upregulation of hypoxia-inducible factor-2α (HIF-2α) and its target genes, erythropoietin (EPO) and endothelin-1, causes polycythemia and pulmonary hypertension in patients with Chuvash polycythemia who are homozygous for the R200W mutation in the von Hippel Lindau (VHL) gene and in a murine mouse model of Chuvash polycythemia that bears the same homozygous VhlR200W mutation. Moreover, the aged VhlR200W mice developed pulmonary fibrosis, most likely due to the increased expression of Cxcl-12, another Hif-2α target. Patients with mutations in iron regulatory protein 1 (IRP1) also develop polycythemia, and Irp1-knockout (Irp1-KO) mice exhibit polycythemia, pulmonary hypertension, and cardiac fibrosis attributable to translational derepression of Hif-2α, and the resultant high expression of the Hif-2α targets EPO, endothelin-1, and Cxcl-12. In this study, we inactivated Hif-2α with the second-generation allosteric HIF-2α inhibitor MK-6482 in VhlR200W, Irp1-KO, and double-mutant VhlR200W;Irp1-KO mice. MK-6482 treatment decreased EPO production and reversed polycythemia in all 3 mouse models. Drug treatment also decreased right ventricular pressure and mitigated pulmonary hypertension in VhlR200W, Irp1-KO, and VhlR200W;Irp1-KO mice to near normal wild-type levels and normalized the movement of the cardiac interventricular septum in VhlR200Wmice. MK-6482 treatment reduced the increased expression of Cxcl-12, which, in association with CXCR4, mediates fibrocyte influx into the lungs, potentially causing pulmonary fibrosis. Our results suggest that oral intake of MK-6482 could represent a new approach to treatment of patients with polycythemia, pulmonary hypertension, pulmonary fibrosis, and complications caused by elevated expression of HIF-2α.
Giampietro PF, Adler-Brecher B, Verlander PC, Pavlakis SG, Davis JG, Auerbach AD	The need for more accurate and timely diagnosis in Fanconi anemia: a report from the International Fanconi Anemia Registry.	Pediatrics 1993, 91: 1116
The objective of this study was to address the need for early diagnosis of Fanconi anemia (FA), an autosomal recessive chromosomal instability syndrome characterized by a unique cellular hypersensitivity to DNA cross-linking agents, such as diepoxybutane, and by a high risk of malignancies.
Giardino S, de Latour RP, Aljurf M, Eikema DJ, Bosman P, Bertrand Y, Tbakhi A, Holter W, Bornhäuser M, Rössig C, Burkhardt B, Zecca M, Afanasyev B, Michel G, Ganser A, Alseraihy A, Ayas M, Uckan-Cetinkaya D, Bruno B, Patrick K, Bader P, Itälä-Remes M, Rocha V, Jubert C, Diaz MA, Shaw PJ, Junior LGD, Locatelli F, Kröger N, Faraci M, Pierri F, Lanino E, Miano M, Risitano A, Robin M, Dufour C, Severe Aplastic Anemia and Chronic Malignancies Working Parties of European Blood and Marrow Transplantation group	Outcome of patients with Fanconi anemia developing myelodysplasia and acute leukemia who received allogeneic hematopoietic stem cell transplantation: A retrospective analysis on behalf of EBMT group.	American journal of hematology 2020, 95: 809
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is curative for bone marrow failure in patients with Fanconi anemia (FA), but the presence of a malignant transformation is associated with a poor prognosis and the management of these patients is still challenging. We analyzed outcome of 74 FA patients with a diagnosis of myelodysplastic syndrome (n = 35), acute leukemia (n = 35) or with cytogenetic abnormalities (n = 4), who underwent allo-HSCT from 1999 to 2016 in EBMT network. Type of diagnosis, pre-HSCT cytoreductive therapies and related toxicities, disease status pre-HSCT, donor type, and conditioning regimen were considered as main variables potentially influencing outcome. The 5-year OS and EFS were 42% (30-53%) and 39% (27-51%), respectively. Patients transplanted in CR showed better OS compared with those transplanted in presence of an active malignant disease (OS:71%[48-95] vs 37% [24-50],P = .04), while none of the other variables considered had an impact. Twenty-two patients received pre-HSCT cytoreduction and 9/22 showed a grade 3-4 toxicity, without any lethal event or negative influence on survival after HSCT(OS:toxicity pre-HSCT 48% [20-75%] vs no-toxicity 51% [25-78%],P = .98). The cumulative incidence of day-100 grade II-IV a-GvHD and of 5-year c-GvHD were 38% (26-50%) and 40% (28-52%). Non-relapse-related mortality and incidence of relapse at 5-years were 40% (29-52%) and 21% (11-30%) respectively, without any significant impact of the tested variables. Causes of death were transplant-related events in most patients (34 out of the 42 deaths, 81%). This analysis confirms the poor outcome of transformed FA patients and identifies the importance of achieving CR pre-HSCT, suggesting that, in a newly diagnosed transformed FA patient, a cytoreductive approach pre-HSCT should be considered if a donor have been secured.
Gianferante MD, Wlodarski MW, Atsidaftos E, Da Costa L, Delaporta P, Farrar JE, Goldman FD, Hussain M, Kattamis A, Leblanc T, Lipton JM, Niemeyer CM, Pospisilova D, Quarello P, Ramenghi U, Sankaran VG, Vlachos A, Volejnikova J, Alter BP, Savage SA, Giri N	Genotype-phenotype association and variant characterization in Diamond-Blackfan anemia caused by pathogenic variants in RPL35A.	Haematologica 2021, 106: 1303
Diamond Blackfan anemia (DBA) is predominantly an autosomal dominant inherited red cell aplasia primarily caused by pathogenic germline variants in ribosomal protein genes. DBA due to pathogenic RPL35A variants has been associated with large 3q29 deletions and phenotypes not common in DBA. We conducted a multi-institutional genotype-phenotype study of 45 patients with DBA associated with pathogenic RPL35A germline variants and curated the variant data on 21 additional cases from the literature. Genotype-phenotype analyses were conducted comparing patients with large deletions versus all other pathogenic variants in RPL35A. Twenty-two of the 45 cases had large deletions in RPL35A. After adjusting for multiple tests, a statistically significant association was observed between patients with a large deletion and steroid-resistant anemia, neutropenia, craniofacial abnormalities, chronic gastrointestinal problems, and intellectual disabilities (p<0.01) compared with all other pathogenic variants. Non-large deletion pathogenic variants were spread across RPL35A with no apparent hot spot and 56% of the individual family variants were observed more than once. In this, the largest known study of DBA patients with pathogenic RPL35A variants, we determined that patients with large deletions have a more severe phenotype that is clinically different from those with non-large deletion variants. Genes of interest also deleted in the 3q29 region that could be associated with some of these phenotypic features include LMLN and IQCG. Management of DBA due to large RPL35A deletions may be challenging due to complex problems and require comprehensive assessments by multiple specialists including immunologic, gastrointestinal, and developmental evaluations to provide optimal multidisciplinary care.
Gialesaki S, Bräuer-Hartmann D, Issa H, Bhayadia R, Alejo-Valle O, Verboon L, Schmell AL, Laszig S, Regényi E, Schuschel K, Labuhn M, Ng M, Winkler R, Ihling C, Sinz A, Glaß M, Hüttelmaier S, Matzk S, Schmid L, Strüwe FJ, Kadel SK, Reinhardt D, Yaspo ML, Heckl D, Klusmann JH	RUNX1 isoform disequilibrium promotes the development of trisomy 21-associated myeloid leukemia.	Blood 2023, 141: 1105
Gain of chromosome 21 (Hsa21) is among the most frequent aneuploidies in leukemia. However, it remains unclear how partial or complete amplifications of Hsa21 promote leukemogenesis and why children with Down syndrome (DS) (ie, trisomy 21) are particularly at risk of leukemia development. Here, we propose that RUNX1 isoform disequilibrium with RUNX1A bias is key to DS-associated myeloid leukemia (ML-DS). Starting with Hsa21-focused CRISPR-CRISPR-associated protein 9 screens, we uncovered a strong and specific RUNX1 dependency in ML-DS cells. Expression of the RUNX1A isoform is elevated in patients with ML-DS, and mechanistic studies using murine ML-DS models and patient-derived xenografts revealed that excess RUNX1A synergizes with the pathognomonic Gata1s mutation during leukemogenesis by displacing RUNX1C from its endogenous binding sites and inducing oncogenic programs in complex with the MYC cofactor MAX. These effects were reversed by restoring the RUNX1A:RUNX1C equilibrium in patient-derived xenografts in vitro and in vivo. Moreover, pharmacological interference with MYC:MAX dimerization using MYCi361 exerted strong antileukemic effects. Thus, our study highlights the importance of alternative splicing in leukemogenesis, even on a background of aneuploidy, and paves the way for the development of specific and targeted therapies for ML-DS, as well as for other leukemias with Hsa21 aneuploidy or RUNX1 isoform disequilibrium.
Gieseke F, Schütt B, Viebahn S, Koscielniak E, Friedrich W, Handgretinger R, Müller I	Human multipotent mesenchymal stromal cells inhibit proliferation of PBMCs independently of IFNgammaR1 signaling and IDO expression.	Blood 2007, 110: 2197
Multipotent mesenchymal stromal cells (MSCs) inhibit proliferation, helper, and effector functions in most if not all peripheral blood mononuclear cell (PBMC) subpopulations in vitro. The molecular mechanism is widely thought to imply tryptophan degradation by the interferon-gamma (IFNgamma)-induced expression of indoleamine 2,3-dioxygenase (IDO). However, IDO inhibitors were not able to restore proliferation of PBMCs in each case. Moreover, human MSCs with an IFNgamma receptor 1 (R1) defect inhibited proliferation of HLA-mismatched PBMCs to a similar extent as control MSCs. In contrast to healthy MSCs, IFNgammaR1-deficient MSCs showed no detectable mRNA for IDO-neither in the absence nor in the presence of recombinant human IFNgamma, nor in coculture with HLA-mismatched PBMCs. Based on gene expression profiling, we were able to show that insulin-like growth factor (IGF)-binding proteins contribute to the inhibitory mechanism of MSCs. Taken together, human MSCs exert important immunomodulatory functions in the absence of IFNgammaR1 signaling and IDO, partially accounted for by IGF-binding proteins.
Gielen GH, Gessi M, Hammes J, Kramm CM, Waha A, Pietsch T	H3F3A K27M mutation in pediatric CNS tumors: a marker for diffuse high-grade astrocytomas.	American journal of clinical pathology 2013, 139: 345
Brain tumors are one of the most common childhood malignancies. Diffuse high-grade gliomas represent approximately 10% of pediatric brain tumors. Exon sequencing has identified a mutation in K27M of the histone H3.3 gene (H3F3A K27M and G34R/V) in about 20% of pediatric glioblastomas, but it remains to be seen whether these mutations can be considered specific for pediatric diffuse high-grade astrocytomas or also occur in other pediatric brain tumors. We performed a pyrosequencing-based analysis for the identification of H3F3A codon 27 and codon 34 mutations in 338 pediatric brain tumors. The K27M mutation occurred in 35 of 129 glioblastomas (27.1%) and in 5 of 28 (17.9%) anaplastic astrocytomas. None of the other tumor entities showed H3F3A K27M mutation. Because H3F3A K27M mutations occur exclusively in pediatric diffuse high-grade astrocytomas, analysis of codon 27 mutational status could be useful in the differential diagnosis of these neoplasms.
Ginsberg J, de Alava E, Ladanyi M, Wexler L, Kovar H, Paulussen M, Zoubek A, Jürgens H, Wunder J, Andrulis I, Malik R, Sorensen P, Womer R, Barr F	EWS-FLI1 and EWS-ERG gene fusions are associated with similar clinical phenotypes in Ewing's sarcoma.	J Clin Oncol 1999, 17: 1809
Ginzburg Y, Rivella S	{beta}-thalassemia: a model for elucidating the dynamic regulation of ineffective erythropoiesis and iron metabolism.	Blood 2011, 118: 4321
β-thalassemia is a disease characterized by anemia and is associated with ineffective erythropoiesis and iron dysregulation resulting in iron overload. The peptide hormone hepcidin regulates iron metabolism, and insufficient hepcidin synthesis is responsible for iron overload in minimally transfused patients with this disease. Understanding the crosstalk between erythropoiesis and iron metabolism is an area of active investigation in which patients with and models of β-thalassemia have provided significant insight. The dependence of erythropoiesis on iron presupposes that iron demand for hemoglobin synthesis is involved in the regulation of iron metabolism. Major advances have been made in understanding iron availability for erythropoiesis and its dysregulation in β-thalassemia. In this review, we describe the clinical characteristics and current therapeutic standard in β-thalassemia, explore the definition of ineffective erythropoiesis, and discuss its role in hepcidin regulation. In preclinical experiments using interventions such as transferrin, hepcidin agonists, and JAK2 inhibitors, we provide evidence of potential new treatment alternatives that elucidate mechanisms by which expanded or ineffective erythropoiesis may regulate iron supply, distribution, and utilization in diseases such as β-thalassemia.
Giona F, Teofili L, Moleti ML, Martini M, Palumbo G, Amendola A, Mazzucconi MG, Testi AM, Pignoloni P, Orlando SM, Capodimonti S, Nanni M, Leone G, Larocca LM, Foà R	Thrombocythemia and polycythemia in patients younger than 20 years at diagnosis: clinical and biologic features, treatment, and long-term outcome.	Blood 2012; 119: 2219
Sixty-four patients < 20 years of age, investigated for a suspicion of Philadelphia-negative myeloproliferative disease (MPD), were retrospectively evaluated to characterize the different forms and to examine the treatments used and long-term outcome. JAK2 mutations, endogenous erythroid colony growth, and clonality were investigated in 51 children. Mutations of thrombopoietin, the thrombopoietin receptor (MPL), and the erythropoietin receptor and mutations of other genes involved in the pathogenesis of MPD were investigated in JAK2 wild-type patients. Based on our criteria for childhood MPD, we identified 34 patients with sporadic thrombocythemia (ST), 16 with hereditary thrombocytosis (HT), 11 with sporadic polycythemia (SP), and 3 with hereditary polycythemia (HP). JAK2(V617F) mutations were present in 47.5% of ST and in no HT. The MPL(S505A) mutation was detected in 15/16 HT patients and in no ST (P < .00001). The JAK2(V617F) mutation occurred in 27% of SP patients diagnosed according to the Polycythemia Vera Study Group or World Health Organization 2001 criteria. Children with ST received more cytoreductive drugs than those with HT (P = .0006). After a median follow-up of 124 months, no patient had developed leukemia or myelofibrosis and 5% had thrombosis; the miscarriage rate in thrombocythemic patients was 14%. The low complication rate in our population suggests that children with MPD may be managed by tailored approaches.
Giri N, Batista DL, Alter BP, Stratakis CA	Endocrine abnormalities in patients with Fanconi anemia.	J Clin Endocrinol Metab 2007, 92: 2624
Fanconi anemia (FA) is an inherited disorder with chromosomal instability, bone marrow failure, developmental defects, and a predisposition to cancer. Systematic and comprehensive endocrine function data in FA are limited.
Girelli D, Busti F, Brissot P, Cabantchik I, Muckenthaler MU, Porto G	Hemochromatosis classification: update and recommendations by the BIOIRON Society.	Blood 2022, 139: 3018
Hemochromatosis (HC) is a genetically heterogeneous disorder in which uncontrolled intestinal iron absorption may lead to progressive iron overload (IO) responsible for disabling and life-threatening complications such as arthritis, diabetes, heart failure, hepatic cirrhosis, and hepatocellular carcinoma. The recent advances in the knowledge of pathophysiology and molecular basis of iron metabolism have highlighted that HC is caused by mutations in at least 5 genes, resulting in insufficient hepcidin production or, rarely, resistance to hepcidin action. This has led to an HC classification based on different molecular subtypes, mainly reflecting successive gene discovery. This scheme was difficult to adopt in clinical practice and therefore needs revision. Here we present recommendations for unambiguous HC classification developed by a working group of the International Society for the Study of Iron in Biology and Medicine (BIOIRON Society), including both clinicians and basic scientists during a meeting in Heidelberg, Germany. We propose to deemphasize the use of the molecular subtype criteria in favor of a classification addressing both clinical issues and molecular complexity. Ferroportin disease (former type 4a) has been excluded because of its distinct phenotype. The novel classification aims to be of practical help whenever a detailed molecular characterization of HC is not readily available.
Glaser SL, Lin RJ, Stewart SL, Ambinder RF, Jarrett RF, Brousset P, Pallesen G, Gulley ML, Khan G, O'Grady J, Hummel M, Preciado MV, Knecht H, Chan JK, Claviez A	Epstein-Barr virus-associated Hodgkin's disease: epidemiologic characteristics in international data.	Int J Cancer 1997, 70: 375
Gladwin MT, Barst RJ, Gibbs JS, Hildesheim M, Sachdev V, Nouraie M, Hassell KL, Little JA, Schraufnagel DE, Krishnamurti L, Novelli E, Girgis RE, Morris CR, Berman Rosenzweig E, Badesch DB, Lanzkron S, Castro OL, Taylor JG 6th, Goldsmith JC, Kato GJ, Gordeuk VR, Machado RF, walk-PHaSST Investigators and Patients	Risk factors for death in 632 patients with sickle cell disease in the United States and United Kingdom.	PloS one 2014, 9:e99489
The role of pulmonary hypertension as a cause of mortality in sickle cell disease (SCD) is controversial.
Gleeson HK, Shalet SM	The impact of cancer therapy on the endocrine system in survivors of childhood brain tumours.	Endocrine-related cancer 2004, 11: 589
Survival rates are improving following cancer therapy for childhood brain tumours. There is therefore a growing cohort of survivors at risk of late effects of cancer therapy. Endocrine problems are very common in these patients. The recognition and prompt management of these are essential to prevent further morbidity and impairment of quality of life. Cranial radiation can damage hypothalamic-pituitary function, most frequently affecting GH status; however, higher radiation doses may cause more widespread hypothalamic-pituitary damage. Early puberty secondary to cranial irradiation is now being managed with gonadotrophin-releasing hormone analogues to improve final height. Prompt diagnosis and management of GH deficiency may improve final height outcome; continued GH therapy beyond final height aids the achievement of adult body composition (lean body mass and bone mass) and GH therapy in adulthood improves quality of life. Both cranial irradiation alone and with spinal irradiation can result in radiation damage to the thyroid resulting in hypothyroidism and thyroid nodules, a high proportion of which are malignant. Gonadal damage secondary to spinal irradiation and adjuvant chemotherapy may have long-term consequences including infertility.
Gluckman E, Cappelli B, Bernaudin F, Labopin M, Volt F, Carreras J, Pinto Simões B, Ferster A, Dupont S, de la Fuente J, Dalle JH, Zecca M, Walters MC, Krishnamurti L, Bhatia M, Leung K, Yanik G, Kurtzberg J, Dhedin N, Kuentz M, Michel G, Apperley J, Lutz P, Neven B, Bertrand Y, Vannier JP, Ayas M, Cavazzana M, Matthes-Martin S, Rocha V, Elayoubi H, Kenzey C, Bader P, Locatelli F, Ruggeri A, Eapen M, Eurocord, the Pediatric Working Party of the European Society for Blood and Marrow Transplantation, and the Center for International Blood and Marrow Transplant Research	Sickle cell disease: an international survey of results of HLA-identical sibling hematopoietic stem cell transplantation.	Blood 2017, 129: 1548
Despite advances in supportive therapy to prevent complications of sickle cell disease (SCD), access to care is not universal. Hematopoietic cell transplantation is, to date, the only curative therapy for SCD, but its application is limited by availability of a suitable HLA-matched donor and lack of awareness of the benefits of transplant. Included in this study are 1000 recipients of HLA-identical sibling transplants performed between 1986 and 2013 and reported to the European Society for Blood and Marrow Transplantation, Eurocord, and the Center for International Blood and Marrow Transplant Research. The primary endpoint was event-free survival, defined as being alive without graft failure; risk factors were studied using a Cox regression models. The median age at transplantation was 9 years, and the median follow-up was longer than 5 years. Most patients received a myeloablative conditioning regimen (n = 873; 87%); the remainder received reduced-intensity conditioning regimens (n = 125; 13%). Bone marrow was the predominant stem cell source (n = 839; 84%); peripheral blood and cord blood progenitors were used in 73 (7%) and 88 (9%) patients, respectively. The 5-year event-free survival and overall survival were 91.4% (95% confidence interval, 89.6%-93.3%) and 92.9% (95% confidence interval, 91.1%-94.6%), respectively. Event-free survival was lower with increasing age at transplantation (hazard ratio [HR], 1.09; P < .001) and higher for transplantations performed after 2006 (HR, 0.95; P = .013). Twenty-three patients experienced graft failure, and 70 patients (7%) died, with the most common cause of death being infection. The excellent outcome of a cohort transplanted over the course of 3 decades confirms the role of HLA-identical sibling transplantation for children and adults with SCD.
Gnekow A, Kaatsch P, Kortmann R, Wiestler OD	HIT-LGG: Effektivität von Carboplatin-Vincristin bei progredienten Gliomen niedrigen Malignitätsgrades im Kindesalter - Zwischenbericht.	Klin Pädiatr 2000, 212: 177
Gnekow A	Behandlung von Kindern und Jugendlichen mit Gliomen niedrigen Malignitätsgrades.	Klinische Onkologie 2001, 372
Gnekow A	HIT-LGG.	Aktuelle Neuropädiatrie 2001, 377
Gnekow AK	Therapie von Gliomen niedriger Malignität im Kindes- und Jugendalter.	WIR Informationsschrift der Aktion für krebskranke Kinder e.V. (Bonn) 2003, 2: 8
Gnekow AK, Packer RJ, Kortmann RD	Astrocytic tumors, low-grade: general considerations, treatment considerations by primary site and tumor dissemination.	In: Walker DA, Perilongo G, Punt JAG, Taylor RE (Eds) Brain and Spinal Tumors of Childhood Arnold publisher, London, 2004, V: 245 - 276
Gnekow AK, Kortmann RD, Pietsch T, Emser A	Low grade chiasmatic-hypothalamic glioma-carboplatin and vincristin chemotherapy effectively defers radiotherapy within a comprehensive treatment strategy -- report from the multicenter treatment study for children and adolescents with a low grade glioma -- HIT-LGG 1996 -- of the Society of Pediatric Oncology and Hematology (GPOH).	Klinische Padiatrie 2004, 216: 331
BACKGROUND: Low grade gliomas arise in all CNS-locations and age groups, chiasmatic-hypothalamic tumors occur especially in young children. Early radiotherapy (RT) shall be deferred by chemotherapy (CT) within the concept of the HIT-LGG 1996 study, offering a comprehensive treatment strategy for all age groups. PATIENTS: 198 of 905 protocol patients (21.9 %) had a chiasmatic (34), chiasmatic-hypothalamic (144) or hypothalamic (20) primary tumor, median age at diagnosis 3.6 years (0.2-16.3 y.), 54 had neurofibromatosis (27.3 %), 108 female (54.5 %). 98 children had severe visual impairment as their first symptom. The initial neurosurgical intervention resulted in 5 complete, 26 subtotal, 45 partial resections, 67 biopsies; 55 children had a diagnosis on the basis of neuroradiologic findings. Histology showed 132 pilocytic astrocytoma I degrees , 6 astrocytoma II degrees /nos and 2 DIGG/DIA I degrees (3 not known). RESULTS: 82 children were treated at diagnosis, 68 upon clinical or radiological progression following observation times of 3.0 to 115.0 months. RT: 27 children received conventional (18) or interstitial (8) RT (1 not documented) at a median age of 7.3 years; 7 tumors went into further progression. At a median observation time of 50.1 months 21 tumors are stable, 3 regressive (2 not evaluable, 1 death). CT: 123 children received vincristin/carboplatin at a median age of 3.7 years. 105/123 achieved CR/PR/SD. 44/123 tumors were progressive after median 22.5 months, 37 with a chiasmatic-hypothalamic primary, 16/44 were irradiated. At a median observation time of 44.7 months 2 children are in complete remission, 92 tumors are stable, 8 regressive, 9 progressive. 4 children died, 8 are not evaluable. At 60 months overall survival of the cohort is 0.93; PFS of the CT-group is 0.61, the RT-free survival 0.83. Within the CT-group children with an age at diagnosis < 1 year and non-pilocytic histology are at increased risk for early progression. Causative factors cannot be defined, yet. CONCLUSION: Within the comprehensive treatment strategy for low grade glioma HIT-LGG 1996 chemotherapy is effective to delay the need for early radiotherapy in chiasmatic-hypothalamic glioma. More effective reduction of the risk for progression has to be sought for young children < 1 year.
Gnekow AK, Scheiderbauer J, Pietsch T, Soerensen N, Faldum A, Emser A, von Hornstein S, Warmuth-Metz M, Kuehl J	HIT-LGG 1996-Success of a countrywide, comprehensive treatment strategy for children and adolescents with low grade glioma of all histologies and locations.	Pedriatric Blood and Cancer 2005, 45: 465
Gnekow AK, Falkenstein F, von Hornstein S, Zwiener I, Berkefeld S, Bison B, Warmuth-Metz M, Driever PH, Soerensen N, Kortmann RD, Pietsch T, Faldum A	Long-term follow-up of the multicenter, multidisciplinary treatment study HIT-LGG-1996 for low-grade glioma in children and adolescents of the German Speaking Society of Pediatric Oncology and Hematology.	Neuro-oncology 2012, 14: 1265
The Hirntumorstudien (HIT)-LGG-1996 protocol offered a comprehensive treatment strategy for pediatric patients with low-grade glioma (LGG), ie, observation, surgery, adjuvant radiotherapy, and chemotherapy to defer the start of irradiation in young children. In this current study, we sought to determine clinical factors for progression and survival. Between October 1, 1996 and March 31, 2004, 1031 patients were prospectively recruited into an observation arm (n = 668) and a nonsurgical arm stratifying 12 months of vincristine-carboplatin chemotherapy (n = 216) and conventional radiotherapy/brachytherapy (n = 147) in an age-dependent manner. Median patient age was 6.9 years; 28 patients had diencephalic syndrome, 44 had dissemination, and 108 had neurofibromatosis type 1(NF-1). Main tumor location was the supratentorial midline (40.4%), and the main histology was pilocytic astrocytoma (67.9%). Following a median observation of 9.3 years, 10-year overall survival (OS) was 0.94 and 10-year event-free survival (EFS) was 0.47. Ten-year progression-free survival was 0.62 following radiotherapy and 0.44 following chemotherapy. Sixty-one of 216 chemotherapy patients received radiotherapy 0.3-8.7 years after initial diagnosis. By multivariate analysis, diencephalic syndrome and incomplete resection were found to be unfavorable factors for OS and EFS, age ≥11 years for OS, and supratentorial midline location for EFS. Dissemination, age <1 year, and nonpilocytic histology were unfavorable factors for progression following radiotherapy (138 patients); and diencephalic syndrome, dissemination, and age ≥11 years were unfavorable factors following chemotherapy (210 patients). NF-1 patients and boys experienced prolonged tumor stabilization with chemotherapy. A nationwide multimodal treatment strategy is feasible for pediatric LGG. Extended follow-up yielded results comparable to single-institution series for the treatment groups. Three-quarters of surviving chemotherapy patients have not yet received radiation therapy. Infants with or without diencephalic syndrome and dissemination bear the highest risk for death and progression following diagnosis or treatment.
Gnekow AK, Walker DA, Kandels D, Picton S, Giorgio Perilongo, Grill J, Stokland T, Sandstrom PE, Warmuth-Metz M, Pietsch T, Giangaspero F, Schmidt R, Faldum A, Kilmartin D, De Paoli A, De Salvo GL, of the Low Grade Glioma Consortium and the participating centers	A European randomised controlled trial of the addition of etoposide to standard vincristine and carboplatin induction as part of an 18-month treatment programme for childhood (≤16 years) low grade glioma - A final report.	European journal of cancer (Oxford, England : 1990) 2017, 81: 206
Gnekow AK	Gliome niedrigen Malignitätsgrades im Kindes- und Jugendalter.	Leitlinie der Gesellschaft für Pädiatrische Onkologie und Hämatologie 2018
Gnekow AK, Walker DA, Kandels D, Picton S, Giorgio Perilongo, Grill J, Stokland T, Sandstrom PE, Warmuth-Metz M, Pietsch T, Giangaspero F, Schmidt R, Faldum A, Kilmartin D, De Paoli A, De Salvo GL, Low Grade Glioma Consortium and the participating centers	Corrigendum to "A European randomised controlled trial of the addition of etoposide to standard vincristine and carboplatin induction as part of an 18-month treatment programme for childhood (≤16 years) low grade glioma - A final report".	European journal of cancer 2018, 90: 156
Gnekow AK, Kandels D, Tilburg CV, Azizi AA, Opocher E, Stokland T, Driever PH, Schouten-van Meeteren AYN, Thomale UW, Schuhmann MU, Czech T, Goodden JR, Warmuth-Metz M, Bison B, Avula S, Kortmann RD, Timmermann B, Pietsch T, Witt O	SIOP-E-BTG and GPOH Guidelines for Diagnosis and Treatment of Children and Adolescents with Low Grade Glioma.	Klinische Padiatrie 2019, 231: 107
Low grade gliomas (LGGs) constitute the largest, yet clinically and (molecular-) histologically heterogeneous group of pediatric brain tumors of WHO grades I and II occurring throughout all pediatric age groups and at all central nervous system (CNS) sites. The tumors are characterized by a slow growth rate and may show periods of growth arrest. Around 40% of all LGG patients can be cured by complete neurosurgical resection and are followed by close observation. In case of relapse, second resection often is possible. Following incomplete resection observation is recommended, as long as there is no radiologic tumor growth and the patient does not suffer from significant, tumor-related symptoms. This also applies to patients with a diagnosis of LGG on the basis of radiological criteria. By contrast, clinical worsening and / or radiologic progression are an indication to treatment with either chemo- or radiotherapy. Overall survival is around 90%, and many patients survive with residual tumor, i.Ã¢ÂÂe. they suffer from chronic disease. All patients need comprehensive neuro-oncological care, the principles and details of which are summarized in the current guidelines. These represent standard of care for diagnostic work-up (including neuroimaging and neuropathology), and for therapeutic decisions (including the indications to non-surgical treatment) as well as concepts for neurosurgical intervention, chemotherapy and radiotherapy as well as surveillance and rehabilitation. The current treatment algorithm was compiled by members of the LGG working group of the SIOP-E brain tumor group (SIOP-E-BTG) and is based upon the results of previous European LGG studies and international reports.
Gnekow AK, Kandels D, Tilburg CV, Azizi AA, Opocher E, Stokland T, Driever PH, Schouten-van Meeteren AYN, Thomale UW, Schuhmann MU, Czech T, Goodden JR, Warmuth-Metz M, Bison B, Avula S, Kortmann RD, Timmermann B, Pietsch T, Witt O	Correction: SIOP-E-BTG and GPOH Guidelines for Diagnosis and Treatment of Children and Adolescents with Low Grade Glioma.	Klinische Padiatrie 2019, 231:e2
Gnekow AK, Kandels D, Pietsch T, Bison B, Warmuth-Metz M, Thomale UW, Kortmann RD, Timmermann B, Driever PH, Witt O, Schmidt R, Spix C	Doubling Recruitment of Pediatric Low-grade Glioma within Two Decades does not change Outcome - Report from the German LGG Studies.	Klinische Padiatrie 2021, 233: 107
Successive multicenter studies for pediatric low-grade glioma (LGG) in Germany were accompanied by a doubling of annual recruitment over 2 decades. We investigated whether this increase conveyed a change of epidemiologic characteristics or survival.
Gnoth C, Godehardt E, Frank-Herrmann P, Friol K, Tigges J, Freundl G	Definition and prevalence of subfertility and infertility.	Human reproduction (Oxford, England) 2005, 20: 1144
A common definition of sub- and infertility is very important for the appropriate management of infertility. Subfertility generally describes any form of reduced fertility with prolonged time of unwanted non-conception. Infertility may be used synonymously with sterility with only sporadically occurring spontaneous pregnancies. The major factor affecting the individual spontaneous pregnancy prospect is the time of unwanted non-conception which determines the grading of subfertility. Most of the pregnancies occur in the first six cycles with intercourse in the fertile phase (80%). After that, serious subfertility must be assumed in every second couple (10%) although--after 12 unsuccessful cycles--untreated live birth rates among them will reach nearly 55% in the next 36 months. Thereafter (48 months), approximately 5% of the couples are definitive infertile with a nearly zero chance of becoming spontaneously pregnant in the future. With age, cumulative probabilities of conception decline because heterogeneity in fecundity increases due to a higher proportion of infertile couples. In truly fertile couples cumulative probabilities of conception are probably age independent. Under appropriate circumstances a basic infertility work-up after six unsuccessful cycles with fertility-focused intercourse will identify couples with significant infertility problems to avoid both infertility under- and over-treatment, regardless of age: Couples with a reasonably good prognosis (e.g. unexplained infertility) may be encouraged to wait because even with treatment they do not have a better chance of conceiving. The others may benefit from an early resort to assisted reproduction treatment.
Gobrecht O, Göbel U, Graubner U, Gutjahr P, Schock V, Spaar H, Janka-Schaub G	Effect of dose intensity and therapy-induced leukocytopenia in intensive therapy on the prognosis of acute lymphatic leukemia in childhood. Results in 213 patients of the COALL-85 study.	Klin Pädiatr 1992, 204: 230
Godzinski J, Moorman-Voestermans C, Sawicz-Birkowska K, Tournade M, Voute P, de Kraker J, Weirich A, Ludwig R, Gauthier F	Paediatric surgical oncology. 5--Nephroblastoma. International Society of Paediatric Oncology (SIOP) Nephroblastoma Trial & Study Committee.	Eur J Surg Oncol 1995, 21: 414
Goddard AG, Kingston JE, Hungerford JL	Delay in diagnosis of retinoblastoma: risk factors and treatment outcome.	The British journal of ophthalmology 1999, 83: 1320
BACKGROUND: Delay in diagnosis of retinoblastoma causes considerable parental distress; however, the primary healthcare professional (PHP) may have difficulty detecting the most common presenting symptom-leucocoria. Alternatively, the PHP may not appreciate that retinoblastoma is the pathology underlying more common ocular symptoms in infants and young children. METHOD: The parents of 100 recently diagnosed patients with retinoblastoma were interviewed to establish the extent of diagnostic delay, ascertain any associated risk factors, and to determine whether or not delay influenced treatment outcome. RESULTS: Although nearly 50% of patients were referred to an ophthalmologist within 1 week of first consulting a PHP, one quarter waited more than 8 weeks. There was a significantly increased risk of diagnostic delay in younger patients, those presenting with squint rather than leucocoria, and those first presenting to a health visitor rather than to a general practitioner. The risk of local tumour invasion was significantly increased by diagnostic delay. Treatment with primary enucleation was not increased by diagnostic delay. There were no deaths during the study period. CONCLUSION: Primary healthcare professionals require education about the importance of ocular symptoms, especially squint, in paediatric patients.
Godzinski J, Weirich A, Tournade M, Gauthier F, Buerger D, Moorman-Voestermans C, de Kraker J, Voute P, Ludwig R, Sawicz-Birkowska K, Vujanic G, Ducourtieux M	Primary nephrectomy for emergency.	Eur J Pediatr Surg 2001, 11: 36
Göbel U, Kornhuber B, Schellong G, Winkler K	Empfehlungen zur Struktur und Ausstattung Pädiatrisch-Onkologischer Zentren.	Klin Pädiatr. 1991; 203
Göbel U, Calaminus G, Harms D	[Germ cell tumors in children and adolescents].	Praxis 1995 Sep 26; 84: 1063
3.7% of the diagnoses in the Pediatric Tumour Registry (Zentrales Tumor-Register) of the German Society for Pediatric Oncology and Haematology (Gesellschaft für Pädiatrische Onkologie und Hämatologie) concern germ cell tumors. The annual incidence has increased from 0.22 in 1980 to 0.60 per 100,000 children in 1992. The most common localizations are the coccygeal region (25%), followed by the testes (20%), the ovaries (20%) or the brain (20%). Some malignant germ cell tumors tend to secret the tumour markers Alpha-1-Feto-protein and HCG, and may then be diagnosed clinically due to the increased serum or spinal fluid levels. In the cases of extensive tumors growth and secreting intracranial germ cell tumors, a preoperative chemotherapy is favourable. The latest chemotherapy regime containing Cis-Platinum allows us to achieve long term remission in 80% of cases. Risk factors for the regime include histology, localization stage, and incomplete resection of the primary tumors.
Göbel U, Calaminus G, Blohm M, Booss D, Felberbauer F, Hofmann U, Holschneider AM, Willnow U, Harms D	Extracranial non-testicular teratoma in childhood and adolescence: introduction of a risk score for stratification of therapy.	Klinische Padiatrie 1997, 209: 228
PATIENTS AND METHODS: According to previous literature incomplete tumor resection, coccygeal or ovarian primary site and immaturity are known risk factors for relapse in teratoma. To establish a risk score points are allocated for resection, primary site and histology in the following manner and added: incomplete resection 4 points, primary site coccyx 3 points, ovary 2 points, other site 1 point, histological grading 0-3 points. This score system is evaluated on 270 extracranial non-testicular teratoma cases collected between 1982 and 1995 in the MAKEI cooperative treatment protocols of the German Society of Pediatric Oncology and Hematology. Treatment was resection alone (230 patients) or resection followed by postoperative adjuvant chemotherapy (40 patients). RESULTS: Patients treated with surgery alone: 28/230 (12%) patients relapsed, 14/230 (6%) patients showed highly malignant histology (mostly yolk sac tumor) in relapse. Mortality in case of relapse was 6/28 (21%). Patients scoring > or = 6 points (n = 45) had a relapse rate of 21/45 (47%) resulting in a 23%-mortality (5/21). Patients scoring < 6 points (n = 185) had a 4%-relapse risk (8/185) resulting in 13%-mortality (1/8) (p < 0.01). Patients treated with surgery and adjuvant chemotherapy: 7/40 patients (18%) suffered a relapse, none of them showing malignant histology. Mortality rate in case of relapse was 3/7 (43%). Patients scoring > or = 6 points initially treated with adjuvant chemotherapy (n = 18) had a relapse rate of 7/18 (39%), compared to patients scoring < 6 points (n = 22), in whom no relapses occurred (p < 0.01). There were no highly malignant relapses in the group treated with adjuvant chemotherapy. Regardless of the scored points the difference in highly malignant relapse histology comparing the group treated with surgery and adjuvant chemotherapy to the group treated with surgery was statistically significant (p = 0.02). CONCLUSION: The risk score system marks a high risk group including 63/270 (23%) of all evaluated extracranial non-testicular teratoma cases (scoring > or = 6 points). In this group 28/35 (80%) of relapses and 8/9 (89%) of tumor deaths occurred. For this high risk group a randomized trial will be suggested to evaluate the effect of adjuvant chemotherapy on the rate of malignant relapses. It should also be investigated, if adjuvant chemotherapy will influence relapse rate and mortality.
Göring HD, Bork K, Späth PJ, Bauer R, Ziemer A, Hintner H, Wüthrich B	Untersuchungen zum hereditären Angioödem im deutschsprachigen Raum.	Hautarzt 1998, 49: 114–22
Göbel U, Schneider DT, Calaminus G, Haas RJ, Schmidt P, Harms D	Germ-cell tumors in childhood and adolescence. GPOH MAKEI and the MAHO study groups.	Annals of oncology : official journal of the European Society for Medical Oncology / ESMO 2000, 11: 263
In mature and immature teratoma the treatment is surgical. The risk of recurrence can be estimated from the parameters primary site (with the coccygeal tumors being most at risk), histological grade of immaturity and completeness of the primary resection including the adjacent organ of origin (coccyx, ovary, testis etc.). In case of a microscopically complete tumor resection there is no role for adjuvant chemo- or radiotherapy irrespective of the histological grade of immaturity. Malignant germ-cell tumors (GCT) account for 2.9% of all malignant tumors of children younger than 15 years of age. More than half of the tumors occur at extragonadal sites such as the ovaries (26%), the coccygeal region (24%), the testes (18%) and the brain (18%) represent then primary sites. In patients with extensive tumor growth, metastatic disease or secreting intracranial tumors a delayed tumor resection after preoperative chemotherapy is preferable. In these patients malignant non-seminomatous GCT may be diagnosed clinically due to the increased serum or cerebrospinal fluid levels of the tumor markers AFP and/or beta-HCG. Current risk adapted treatment protocols containing cisplatinum allow long-term remissions in about 80% including patients with bulky or metastatic tumors. In the cisplatinum era the prognostic factors like histology, primary site of the tumor and initial tumor stage have partly lost their former impressive significance in infants and children. On the other hand the completeness of the primary tumor resection according to oncological standards has been established as the most powerful prognostic parameter superior to tumor marker levels or primary site of the tumor.
Göbel U, Schneider DT, Calaminus G, Jürgens H, Spaar HJ, Sternschulte W, Waag K, Harms D	Multimodal treatment of malignant sacrococcygeal germ cell tumors: a prospective analysis of 66 patients of the German cooperative protocols MAKEI 83/86 and 89.	Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2001, 19: 1943
PURPOSE: To evaluate a multimodal approach including surgery and cisplatinum chemotherapy for treatment of children with malignant sacrococcygeal germ cell tumors (GCT) and to compare adjuvant and neoadjuvant strategies in advanced tumors. PATIENTS AND METHODS: Between 1983 and 1995, 71 patients with malignant sacrococcygeal GCT were prospectively enrolled onto the German protocols for nontesticular GCT Maligne Keimzelltumoren 83/86 and 89. Five patients who received no chemotherapy (n = 2) or nonplatinum chemotherapy (n = 2) or who did not undergo tumor resection (n = 1) were excluded from this analysis. Among the 66 patients analyzed were 14 boys and 52 girls. The median age was 17.4 months (range, 7 months to 119 months). Median follow-up was 79 months (range, 4 months to 145 months). RESULTS: Fifty-two patients presented with locally advanced stage T2 tumors, and 30 patients had distant metastases at diagnosis. Patients received a median of eight cycles (range, four to nine cycles) of cisplatinum-based chemotherapy. Thirty-five patients underwent tumor resection at diagnosis and received adjuvant cisplatinum-based chemotherapy (group A). Thirty-one patients received up-front chemotherapy followed by delayed tumor resection (group B). Group B included more metastatic tumors than group A (group B, 19 of 31 patients; group A, 11 of 35 patients, P =.01). Preoperative chemotherapy facilitated complete tumor resections (group B, 20 of 31 patients; group A, five of 35 patients, P <.001) and avoided second-look surgery. Metastases at diagnosis and completeness of the first attempt of tumor resection were significant prognostic predictors; however, metastases were not predictive for patients treated with up-front chemotherapy. At 5 years follow-up, event-free survival was 0.76 +/- 0.05 (50 of 66 patients), and overall survival was 0.81 +/- 0.05 (54 of 66 patients). Four patients died as a result of therapy-related complications, and eight patients died of their tumors. Patients with locally advanced and metastatic tumors (T2b M1) fared better with neoadjuvant treatment [overall survival: 0.83 +/- 0.09 (16 of 19 patients) versus 0.45 +/- 0.15 (five of 11 patients), P =.01]. CONCLUSION: Even locally advanced and metastatic sacrococcygeal GCT can be successfully treated with up-front cisplatinum-based chemotherapy followed by delayed but complete tumor resection.
Goemans BF, Zwaan CM, Martinelli S, Harrell P, de Lange D, Carta C, Reinhardt D, Hahlen K, Creutzig U, Tartaglia M, Heinrich MC, Kaspers GJ	Differences in the prevalence of PTPN11 mutations in FAB M5 paediatric acute myeloid leukaemia.	British journal of haematology 2005, 130: 801
Goemans BF, Zwaan CM, Miller M, Zimmermann M, Harlow A, Meshinchi S, Loonen AH, Hahlen K, Reinhardt D, Creutzig U, Kaspers GJ, Heinrich MC	Mutations in KIT and RAS are frequent events in pediatric core-binding factor acute myeloid leukemia.	Leukemia 2005, 19: 1536
Activating mutations in RAS and receptor tyrosine kinases such as KIT and FLT3 are hypothesized to cooperate with chimeric transcription factors in the pathogenesis of acute myeloid leukemia (AML). To test this hypothesis, we genotyped 150 pediatric AML samples for mutations in KIT (exons 8, 17), NRAS and KRAS (exons 1, 2) and FLT3/ITD. This is the largest cohort of pediatric AML patients reported thus far screened for all four mutations. Of the children with AML, 40% had a mutation in KIT (11.3%), RAS (18%) or FLT3/ITD (11.1%), and 70% of cases of core-binding factor (CBF) leukemia were associated with a mutation of KIT or RAS. Mutations in RAS or FLT3/ITD were frequently found in association with a normal karyotype. Patients with a FLT3/ITD mutation had a significantly worse clinical outcome. However, the presence of a KIT or RAS mutation did not significantly influence clinical outcome. We demonstrate that KIT exon 8 mutations result in constitutive ligand-independent kinase activation that can be inhibited by clinically relevant concentrations of imatinib. Our results demonstrate that abnormalities of signal transduction pathways are frequent in pediatric AML. Future clinical studies are needed to determine whether selective targeting of these abnormalities will improve treatment results.
Goemans BF, Zwaan CM, Harlow A, Loonen AH, Gibson BE, Hahlen K, Reinhardt D, Creutzig U, Heinrich MC, Kaspers GJ	In vitro profiling of the sensitivity of pediatric leukemia cells to tipifarnib: identification of T-cell ALL and FAB M5 AML as the most sensitive subsets.	Blood 2005, 106: 3532
Although the prognosis of pediatric leukemias has improved considerably, many patients still have relapses. Tipifarnib, a farnesyl transferase inhibitor (FTI), was developed to target malignancies with activated RAS, including leukemia. We tested 52 pediatric acute myeloid leukemia (AML) and 36 pediatric acute lymphoblastic leukemia (ALL) samples for in vitro sensitivity to tipifarnib using a total cell-kill assay and compared these results to those obtained with normal bone marrow (N BM) samples (n = 25). AML samples were significantly more sensitive to tipifarnib compared to B-cell precursor ALL (BCP ALL) or N BM samples. Within AML, French-American-British (FAB) M5 samples were most sensitive to tipifarnib. T-cell ALL samples were significantly more sensitive than BCP ALL and N BM samples. In AML there was a marked correlation between tipifarnib resistance and daunorubicin or etoposide resistance, but not to cytarabine or 6-thioguanine. RAS mutations were present in 32% of AML and 18% of ALL samples, but there was no correlation between RAS mutational status and sensitivity to tipifarnib. Future studies are needed to identify biomarkers predictive of tipifarnib sensitivity. In addition, clinical studies, especially in T-cell ALL, seem warranted.
Göbel U, Calaminus G, Schneider DT, Koch S, Teske C, Harms D	The malignant potential of teratomas in infancy and childhood: the MAKEI experiences in non-testicular teratoma and implications for a new protocol.	Klinische Padiatrie 2006, 218: 309
Since 1982, mature and immature teratomas have been recruited into the MAHO and MAKEI protocols of the German Society for Pediatric Oncology and Hematology (GPOH) for testicular and non-testicular germ cell tumors in order to study the epidemiology and clinical behaviour of teratomas. Patients were registered in the epidemiologic German Childrens Cancer Registry and the GPOH Childrens Tumor Registry for pathological review. Patients with immaturity grade 2 and 3 according to Gonzales-Crussi were eligible for adjuvant chemotherapy. The consecutive protocols MAKEI 83/86/89 have been published previously in detail (Klin Paediatr 1997; 209: 228-234, Med Pediat Oncol 1998; 31: 8-15) and will be compared to the data of MAKEI 96. For this comparison, 274 patients from MAKEI 83/86/89 and 261 patients from MAKEI 96 are evaluable. RESULTS: 1) EFS after complete tumor resection has been estimated to 0.96 +/- 0.01 in both observation periods. 2) Incomplete tumor resection remains the main risk factor for relapse (EFS 0.55 +/- 0.09). 3) The relapse rate declined from 13.9 % in MAKEI 83/86/89 to 9.5 % in MAKEI 96. 4) In MAKEI 83/86/89 four newborns with teratoma died due to perioperative complications and nine children as a result of tumor progression, whereas in MAKEI 96 no newborn died, only one child died from tumor progression, and another child died during long time observation for another reason (meningitis). 5) In accordance to the experience of the MAKEI 83/86/89 studies, no child of the MAKEI 96 study presented with yolk sac tumor at recurrence if adjuvant chemotherapy was administered during first-line treatment because of immaturity. In contrast, more than half of the children with tumor recurrence after watch and wait strategy had yolk sac tumor in addition to teratoma.
Göhring G, Karow A, Steinemann D, Wilkens L, Lichter P, Zeidler C, Niemeyer C, Welte K, Schlegelberger B	Chromosomal aberrations in congenital bone marrow failure disorders--an early indicator for leukemogenesis?	Annals of hematology 2007, 86: 733
As chromosomal instability may contribute to leukemogenesis in patients with congenital bone marrow failure (CBMF) disorders, it was the aim of this study to characterize chromosomally aberrant clones that arise during the clinical course of disease by means of R-banding and fluorescence in situ hybridization (FISH) analyses. In addition, multicolor-FISH and array-comparative genomic hybridization (CGH) were applied to characterize clonal chromosome aberrations in more detail. Between January 2004 and December 2005, we prospectively analyzed 90 samples of 73 patients with proven or suspected CBMF disorders enrolled in a German Study Network of CBMF diseases. Clonal aberrations could be identified in four of 73 patients examined. In one child with congenital thrombocytopenia, Jacobsen syndrome [del(11)(q24)c] was diagnosed, and thus a CBMF could be excluded. In a girl with Shwachman-Diamond syndrome, two independent clones, one with an isochromosome i(7)(q10), another with a complex aberrant karyotype, were identified. Simultaneously, transition into a myelodysplastic syndrome (MDS) occurred. The brother, who was also afflicted with Shwachman-Diamond syndrome, showed an isochromosome i(7q) as a single aberration. In the fourth patient with severe congenital neutropenia, an add(21)(q22) marker containing a low-level amplification of the AML1 gene was identified at the time point of transition into acute myelogenous leukemia (AML). In summary, we suggest that follow-up of patients with CBMF using chromosome and FISH analyses will be helpful for the early detection of transition into MDS or AML and thus should be an integral part of the clinical management of these patients.
Goemans BF, Zwaan CM, Cloos J, de Lange D, Loonen AH, Reinhardt D, Hählen K, Gibson BE, Creutzig U, Kaspers GJ	FLT3 and KIT mutated pediatric acute myeloid leukemia (AML) samples are sensitive in vitro to the tyrosine kinase inhibitor SU11657.	Leukemia research 2010,
New treatment strategies to improve the outcome of pediatric acute myeloid leukemia (AML) are required as 40% of children diagnosed with AML do not survive. Around 30% of pediatric AML patients harbour a mutation in the tyrosine kinases FLT3 (+/-20%) or KIT (+/-10%). In this study we investigated whether pediatric AML samples (N=61) were sensitive to the tyrosine kinase inhibitor SU11657 (similar to the clinically available drug sunitinib) in vitro, and whether sensitivity was related to expression of, and mutations in, FLT3 and KIT. Overall, SU11657 showed only moderate cytotoxicity. A FLT3 mutation was detected in 35% and a KIT mutation in 8% of the samples. FLT3 and KIT mutated samples were significantly more sensitive to SU11657 than WT KIT and FLT3 samples. Samples without KIT or FLT3 mutations, but with a high wild-type (WT) KIT expression were significantly more sensitive to SU11657 than samples with low KIT expression. Further clinical evaluation of SU11657 and sunitinib combined with chemotherapy would be of interest. Inclusion in clinical trials should not be restricted to patients with FLT3 or KIT mutations.
Göbel U, Schneider DT, Teske C, Schönberger S, Calaminus G	Brain metastases in children and adolescents with extracranial germ cell tumor - data of the MAHO/MAKEI-registry.	Klinische Padiatrie 2010, 222: 140
BACKGROUND: We analyzed 15 children and adolescents with extracranial germ cell tumor (GCT) and brain metastases reported to the MAHO/MAKEI registry. PATIENTS AND METHODS: Between 1982 and 2009, 2 077 patients were prospectively enrolled onto the MAHO/MAKEI studies (overall survival: 0.88+/-0.03). All patients with advanced malignant GCTs received cisplatin-based chemotherapy (overall survival: 0.81+/-0.04 (734/823). RESULTS: 15 patients with brain metastases were reported; in 6 of them at diagnosis and 9 respectively during follow-up (6 weeks-28 months after end of therapy, mean=10 months). Most patients were male (13/15) and adolescent (10/15). 8 patients suffered from mediastinal GCTs. Pure Choriocarcinoma (CC) or CC in combination with other histologies was diagnosed in 12 patients. Clinical symptoms were reported in most patients. In all patients with secondary brain metastases the previously normalised tumor markers AFP and/ or HCG increased again prior to the onset of neurological symptoms. Only 1 of the patients with primary brain metastases survived, whereas 4 of 9 with secondary metastases are in remission after additional treatment. CONCLUSION: The risk for intracranial metastases increases with age, male gender and mediastinal or testicular primary site and choriocarcinoma histology. Development of neurological symptoms at initial diagnosis or during follow-up should lead to rapid clinical re-evaluation including CNS imaging and assessment of tumor markers. Treatment of brain metastases includes intensified chemotherapy and surgical resection, irradiation has to be considered in special clinical situations.
Goedeke J, Haeberle B, Schmid I, von Schweinitz D	30. AFP Negative Cystic Liver Lesion in a Child Should Let One Think of Hepatoblastoma.	J Pediatr Hematol Oncol 2011, 33:e245
AFP is still the most important serologic marker for the hepatoblastoma as the most common liver tumor in children. An AFP negative hepatoblastoma is rare. We present the first documented case of an infant with an AFP negative and cystic liver lesion later diagnosed as a fetal hepatoblastoma.
Göbel U, von Kries R, Teske C, Schneider DT, Beyerlein A, Bernbeck B, Calaminus G	Brain metastases during follow-up of children and adolescents with extracranial malignant germ cell tumors: Risk adapted management decision tree analysis based on data of the MAHO/MAKEI-registry.	Pediatric blood & cancer 2012, Epub ahead of print
BACKGROUND: The overall risk for brain metastases among children and adolescents with extracranial malignant germ cell tumors (mGCT) is low but may vary between subgroups. Early identification of subgroups with an increased risk for brain metastasis is therefore important. PROCEDURE: We analyzed 900/2,160 patients from the German MAHO/MAKEI registry on children and adolescents with malignant extracranial GCT (pure teratomas (grade 0-3) were not included). For follow-up evaluation, patients with brain metastases at diagnosis and those with a follow-up shorter than 32 months after diagnosis (longest interval to brain metastases in our cohort) were excluded. Patients were censored at detection of brain metastases or death due to other causes. A decision tree analysis considering age, gender, site of primary tumor, and presence of other metastases at diagnosis as risk factors for brain metastases was performed. RESULTS: Among 838 eligible patients, 9 acquired brain metastases during follow-up, accounting for death in 5. There were no brain metastases in absence of extracranial metastases at diagnosis. If extracranial metastases were detected in absence of mediastinal mGCT the risk for brain metastases was 1.2% (95% CI: 0.2-3.5.%). In contrast, risk was increased to 37.5 (95% CI 15.2-64.6%) in patients with mediastinal GCTs and extracranial metastases. CONCLUSION: A high-risk subgroup is detected with a decision tree analysis approach. These patients may benefit from an intensified chemotherapy. Close surveillance for CNS-metastases is warranted in this high-risk group while less close monitoring in low-risk patients is justified. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc.
Göbel U, Calaminus G, Haas R, Teske C, Schönberger S, Schneider DT, Leuschner I, Harms D	Testicular germ cell tumors in adolescents - results of the protocol MAHO 98 and the identification of good risk patients.	Klinische Padiatrie 2014, 226(6-7): 316
In adolescents aged 10-15 years germ cell tumors of the testis (TGCT) are rare and information for a risk adapted therapy limited.
Götte M, Taraks S, Boos J	Sports in pediatric oncology: the role(s) of physical activity for children with cancer.	Journal of pediatric hematology/oncology 2014, 36: 85
Malignant disease and anticancer therapy dramatically affect daily life activities and participation in grassroots and high-performance sports. Specifically in childhood and adolescence such activities are relevant factors of individual development and social life. This review focuses on the inherent reduction of normal physical activity in pediatric oncology because this cutback additionally contributes to the level of burden of malignancies. Maintaining normality requires detailed analyses of disease-related and therapy-related restrictions and their justification. Relevant efforts should be stepped up to maintain physical activity levels during pediatric cancer therapy. Another aspect addresses direct therapeutic implications. Feasibility studies, nonrandomized as well as randomized investigations addressed therapeutic effects in acute hospital care, in bone marrow transplant settings, and in outpatient therapy. The overall summary shows positive effects on clinical and psychosocial outcome. Even if the basis of the data for children is still limited, there will be no doubt about a general impact of physical activity on acute side effects as well as late effects. In the areas of tension between context-related restrictions, the right to maintain normality wherever possible and the positive therapeutic and psychosocial perspectives of sports, strong efforts are needed to support physical activity wherever indicated, clarify contraindications, and overcome structural limitations.
Götte M, Kesting S, Taraks S, Boos J	Rahmenbedingungen individualisierter stationärer Bewegungsförderung in der kinderonkologischen Akutversorgung.	Bewegungstherapie und Gesundheitssport 2015, 31: 117
Goelz R, Poets CF	Incidence and treatment of infantile haemangioma in preterm infants.	Archives of disease in childhood. Fetal and neonatal edition 2015, 100:F85
Gödeke J, Luxenburger E, Trippel F, Becker K, Häberle B, Müller-Höcker J, von Schweinitz D, Kappler R	Low expression of N-myc downstream-regulated gene 2 (NDRG2) correlates with poor prognosis in hepatoblastoma.	Hepatology international 2016, 10: 370
Despite tremendous progress in therapy, about 30% of patients with hepatoblastoma still succumb to the disease. Thus, the development of improved therapies as well as the identification of prognostic factors are urgently needed.
Göhring G, Thomay K, Schmidt G, Ripperger T, Xu M, Wittner N, Chao MM, Baumann I, Niewisch M, Reinhardt D, Klingebiel T, Thol F, Schlegelberger B, Niemeyer CM	A common ancestral DNMT3A-mutated preleukemic clone giving rise to AML and MDS in an adolescent girl.	Leukemia & lymphoma 2017, 58: 718
Goebel AM, Gnekow AK, Kandels D, Witt O, Schmidt R, Hernáiz Driever P	Natural History of Pediatric Low-Grade Glioma Disease - First Multi-State Model Analysis.	Journal of Cancer 2019, 10: 6314
: Pediatric low-grade glioma [PLGG] is often a chronic progressive disease requiring multiple treatments, i.e. surgery, chemotherapy and irradiation. The multi-state model [MSM] allows an extended analysis of disease-states, that patients may undergo, incorporating competing risks over the course of time. : We studied disease-state-probabilities of the German SIOP-LGG 2004 cohort from the initial state
Götte M, Gauß G	Kinder, Jugendliche und Krebs: Netzwerk ActiveOncoKids - Bewegungsförderung und Sporttherapie in der Kinderonkologie.	Aktuelle Gesundheits-Nachrichten der Europäischen Akademie für Naturheilverfahren und Umweltmedizin 38, 2020, 34
Gokarn N, Manwani D, Friedmann P, Borenstein SH, Jan D, Renaud E	Outcomes after early splenectomy for hematological disorders.	Journal of laparoendoscopic & advanced surgical techniques. Part A 2014, 24: 897
Abstract Purpose: Acute splenic sequestration crisis is a devastating complication of sickle cell disease that can require prophylactic splenectomy. Historically, splenectomy before 5 years of age was avoided because of fear of overwhelming postsplenectomy sepsis. Recently, splenectomy has been performed as early as 2 years of age, but the safety of this approach is unknown. This study compared outcomes of splenectomy performed in patients under 5 years of age with those 5 years of age and older.
Goldwein JW, Leahy JM, Packer RJ, Sutton LN, Curran WJ, Rorke LB, Schut L, Littman PS, D'Angio GJ	Intracranial ependymomas in children.	Int J Radiat Oncol Biol Phys 1990, 19: 1497
Between 1970 and 1988, 51 children with intracranial ependymal tumors (33-infratentorial, 18-supratentorial received initial treatment at the University of Pennsylvania. Therapy consisted of total or near total tumor resection in 15 patients and partial resection or biopsy in 36. Postoperative irradiation alone was given to 18, chemotherapy to 4, and a combination of these two modalities to 26. Patients have been followed for a median period of 7.75 years. The 5-year actuarial survival and progression-free survival (PFS) rates are 46% and 30%, respectively. Of the 30 patients who have progressed, 29 did so locally and one died before the site of failure could be determined. Six patients also had disease outside the primary site at relapse; three of them had received craniospinal irradiation. Local control was significantly better for patients whose tumor dose exceeded 4500 cGy (32% vs. 0%, p = .01) and for Caucasian patients (34% vs. 15%, p =.05). Survival was better for patients who were over 4 years of age at diagnosis (55% vs. 30%, p = .04), for patients who received local radiation doses above 4500 cGy (51% vs. 18%, p = .01), and for Caucasian patients (43% vs. 14%, p = .01). Extent of resection, histology, location, the use of cranial or craniospinal irradiation, and the use of chemotherapy did not significantly impact on survival. We conclude that the inability to control local disease remains the single most important factor leading to treatment failure. Older age, higher local radiation dose, and Caucasian race appear to be the only favorable prognostic factors.
Goldwein JW, Corn BW, Finlay JL, Packer RJ, Rorke LB, Schut L	Is craniospinal irradiation required to cure children with malignant (anaplastic) intracranial ependymomas?	Cancer 1991 Jun 1; 67: 2766
Between 1970 and 1989, 17 children with histologically malignant intracranial ependymomas received treatment at the University of Pennsylvania (Philadelphia, PA). Eleven were treated with prophylactic cranial or craniospinal irradiation plus a local boost (CS-XRT), five with local (L-XRT) irradiation only, and one was treated without (NRT) irradiation. With a median survival of 2 years and a median follow-up time for long-term survivors of 6.0 years, five of 11 patients who received CS-XRT are alive compared with none treated with L-XRT and none treated with NRT. Two-year actuarial survival rates are 40% (L-XRT) and 52% (CS-XRT). When examined for other factors, age and local radiation dose remain the most significant prognostic indicators of survival. The 2-year actuarial survival for children younger than 4 years at diagnosis is 20% compared with 83% for their older counterparts. Likewise, the 2-year survival for patients treated with local radiation doses over 4500 cGy was 55% compared with 0% for patients treated with lesser doses. To date there are a total of 28 recurrences. All have occurred with local components except for six (unknown) who died before the exact site(s) could be determined. There is no significant difference in the failure rates outside the original tumor bed in the three groups. These data suggest that local relapse remains the most significant component of failure. Because intrinsic and extrinsic factors such as age and radiation dose seem to be interrelated and at least as important as the use of craniospinal irradiation, the need for prophylactic treatment for children with anaplastic ependymoma could neither be substantiated nor refuted. The use of local radiation alone, however, should be restricted to carefully designed clinical trials in which meticulous pretreatment evaluation is performed, and vigilant posttreatment evaluation of the spine and brain is mandatory.
Goldstein-Jackson SY, Gosheger G, Delling G, Berdel WE, Exner GU, Jundt G, Machatschek JN, Zoubek A, Jürgens H, Bielack SS, Cooperative Osteosarcoma Study Group COSS	Extraskeletal osteosarcoma has a favourable prognosis when treated like conventional osteosarcoma.	Journal of cancer research and clinical oncology 2005, 131: 520
PURPOSE: The aims of this analysis were to investigate the clinical features of extraskeletal osteosarcoma (ESOS) and examine the outcome after multi-modal therapy. METHODS: The co-operative osteosarcoma study-group database was searched for patients with extraskeletal osteosarcoma. Eligible patients were included in a retrospective analysis of patient, tumour and treatment related variables and outcome. As for conventional osteosarcoma, scheduled treatment included surgery and multi-agent chemotherapy. RESULTS: Seventeen eligible patients were identified with a median age of 44 years (range, 3-65 years). The thigh was the commonest tumour site. Two patients had a history of previous malignancies and two had primary metastases. Median follow-up was 3.2 years (range: 0.6-7.4 years) and at last follow-up, 11 patients were alive in complete remission, 3 patients were alive with disease and 3 patients had died of their disease. Three-year overall actuarial and event-free survival rates were 77% and 56%, respectively. Patients with macroscopically complete surgical remission had an improved overall survival (P = 0.0004). CONCLUSIONS: The patients in this retrospective study had a surprisingly good survival rate. This may be due to the combination of multi-agent chemotherapy with surgery, and we recommend this approach in the treatment of ESOS.
Golan DE	Hemolytic Anemias: redcell membrane and metabolic disorders.	In: Goldman, L, Ausiele, D, eds,. Cecil medicine. 23rd. edt., Chap. 165 2007
González-Murillo A, Lozano ML, Alvarez L, Jacome A, Almarza E, Navarro S, Segovia JC, Hanenberg H, Guenechea G, Bueren JA, Río P	Development of lentiviral vectors with optimized transcriptional activity for the gene therapy of patients with fanconi anemia.	Human gene therapy 2010, 21: 623
Fanconi anemia (FA) is an inherited genetic disease characterized mainly by bone marrow failure and cancer predisposition. Although gene therapy may constitute a good therapeutic option for many patients with FA, none of the clinical trials so far developed has improved the clinical status of these patients. We have proposed strategies for the genetic correction of bone marrow grafts from patients with FA, using lentiviral vectors (LVs). Here we investigate the relevance of the expression of FANCA to confer a therapeutic effect in cells from patients with FA-A, the most frequent complementation group in FA. Our data show that relatively weak promoters such as the vav or phosphoglycerate kinase (PGK) promoter confer, per copy of FANCA, physiological levels of FANCA mRNA in lymphoblastoid cell lines, whereas the cytomegalovirus and, more significantly, spleen focus-forming virus (SFFV) promoters mediated the expression of supraphysiological levels of FANCA mRNA. Insertion of the woodchuck hepatitis virus posttranscriptional regulatory element (WPRE) or a mutated WPRE into the 3' region of PGK-FANCA LVs significantly increased FANCA mRNA levels. At the protein level, however, all tested vectors conferred, per copy of FANCA, similar and physiological levels of the protein, except SFFV LVs, which again conferred supraphysiological levels of FANCA. In spite of their different activity, all tested vectors mediated a similar phenotypic correction in FA-A lymphoblastoid cell lines and also in hematopoietic progenitors from patients with FA-A. On the basis of the efficacy and safety properties of PGK LVs, a PGK LV carrying FANCA and a mutant WPRE is proposed as an optimized vector for the gene therapy of patients with FA-A.
Gooskens SL, Segers H, Pritchard-Jones K, Graf N, Dome JS, van den Heuvel-Eibrink MM, van den Heuvel-Eibrink MM	The Clinical Relevance of Age at Presentation in Nephroblastoma.	2016,
The most important prognostic factors for Wilms tumor (WT) patients seem to be stage, histological subtype, and 1p/16q loss of heterozygosity (LOH) in chemotherapy-naive WTs. Over the last decade, age at diagnosis also was suggested to be an important risk factor for WT recurrence in Children’s Oncology Group (COG), United Kingdom (UK), and International Society of Pediatric Oncology (SIOP) studies. Several studies have analyzed age as a prognostic factor; these studies revealed age <2 years as a favorable prognostic factor, while age >4 years has been described as an adverse prognostic factor. In adults (>18 years of age), WT represents less than 1% of all diagnosed renal tumors; therefore, diagnosis of WT in adults is often unexpected and poorly recognized, thereby inducing treatment delay with subsequent adverse outcome. One explanation for the higher risk of recurrence with increasing patient age is the higher frequency of anaplasia at higher age. Other suggested reasons are delay in diagnosis, advanced tumor stage at presentation, and intrinsically different biological behaviors. Whether age is really an independent risk factor, and whether age is a stronger prognostic factor than stage, histology, and LOH 1p/16q, needs to be further explored. This may provide some insight into whether older patients need to be treated more intensively, as is already advised for adult WT patients.
Gore L, Locatelli F, Zugmaier G, Handgretinger R, O'Brien MM, Bader P, Bhojwani D, Schlegel PG, Tuglus CA, von Stackelberg A	Survival after blinatumomab treatment in pediatric patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia.	Blood cancer journal 2018, 8: 80
Goschzik T, Zur Mühlen A, Kristiansen G, Haberler C, Stefanits H, Friedrich C, von Hoff K, Rutkowski S, Pfister SM, Pietsch T	Molecular stratification of medulloblastoma: Comparison of histological and genetic methods to detect Wnt activated tumors.	Neuropathology and applied neurobiology 2014,
Wnt activation in medulloblastomas is associated with good outcome. Upfront testing and risk-adapted stratification of patients will be done in future clinical studies. In a cohort of 186 pediatric medulloblastomas our aim was to identify the optimal methods in standard clinical practice to detect this subgroup.
Goschzik T, Gessi M, Dreschmann V, Gebhardt U, Wang L, Yamaguchi S, Wheeler DA, Lauriola L, Lau CC, Mueller HL, Pietsch T	Genomic Alterations of Adamantinomatous and Papillary Craniopharyngioma.	Journal of neuropathology and experimental neurology 2017, 76: 126
Craniopharyngiomas are rare histologically benign but clinically challenging neoplasms. To obtain further information on the molecular genetics and biology of craniopharyngiomas, we analyzed a cohort of 121 adamantinomatous and 16 papillary craniopharyngiomas (ACP, PCP). We extracted DNA from formalin-fixed paraffin-embedded tissue and determined mutational status of CTNNB1, BRAF, and DDX3X by Sanger sequencing, next generation panel sequencing, and pyrosequencing. Sixteen craniopharyngiomas were further analyzed by molecular inversion profiling (MIP); 76.1% of the ACP were mutated in exon 3 of CTNNB1 encoding for ÃÂ²-catenin and there was a trend towards a worse event-free survival in cases mutated at Thr41. Next generation panel sequencing of 26 ACP did not detect any recurrent mutations other than CTNNB1 mutations. BRAF V600E mutations were found in 94% of the PCP, but not in ACP. GISTIC analysis of MIP data showed no significant larger chromosomal aberrations but a fraction of ACP showed recurrent focal gains of chromosomal material, other cases showed loss in the chromosomal region Xq28, and a third group and the PCP had stable genomes. In conclusion, the crucial pathogenetic event appears to be WNT activation in ACP, whereas it appears to be activation of the Ras/Raf/MEK/ERK pathway by BRAF V600E mutations in PCP.
Goschzik T, Mynarek M, Doerner E, Schenk A, Spier I, Warmuth-Metz M, Bison B, Obrecht D, Struve N, Kortmann RD, Schmid M, Aretz S, Rutkowski S, Pietsch T	Genetic alterations of TP53 and OTX2 indicate increased risk of relapse in WNT medulloblastomas.	Acta neuropathologica 2022, 144: 1143
This study aimed to re-evaluate the prognostic impact of TP53 mutations and to identify specific chromosomal aberrations as possible prognostic markers in WNT-activated medulloblastoma (WNT-MB). In a cohort of 191 patients with WNT-MBs, mutations in CTNNB1, APC, and TP53 were analyzed by DNA sequencing. Chromosomal copy-number aberrations were assessed by molecular inversion probe technology (MIP), SNP6, or 850k methylation array hybridization. Prognostic impact was evaluated in 120 patients with follow-up data from the HIT2000 medulloblastoma trial or HIT registries. CTNNB1 mutations were present in 92.2%, and APC mutations in 6.8% of samples. One CTNNB1 wild-type tumor gained WNT activation due to homozygous FBXW7 deletion. Monosomy 6 was present in 78.6%, and more frequent in children than adults. 16.1% of tumor samples showed TP53 mutations, of those 60% with nuclear positivity for the p53 protein. Loss of heterozygosity at the TP53 locus (chromosome 17p13.1) was found in 40.7% (11/27) of TP53 mutant tumor samples and in 12.6% of TP53 wild-type cases (13/103). Patients with tumors harboring TP53 mutations showed significant worse progression-free survival (PFS; 5-year-PFS 68% versus 93%, p = 0.001), and were enriched for chromosomes 17p (p = 0.001), 10, and 13 losses. Gains of OTX2 (14q22.3) occurred in 38.9% of samples and were associated with poor PFS and OS (5-year-PFS 72% versus 93%, p = 0.017 resp. 5-year-OS 83% versus 97%, p = 0.006). Multivariable Cox regression analysis for PFS/OS identified both genetic alterations as independent prognostic markers. Our data suggest that patients with WNT-MB carrying TP53 mutations or OTX2 gains (58.1%) are at higher risk of relapse. Eligibility of these patients for therapy de-escalation trials needs to be debated.
Gottstein C, Schon G, Tawadros S, Kube D, Wargalla-Plate U, Hansmann M, Wacker H, Berthold F, Diehl V, Engert A	Antidisialoganglioside ricin A-chain immunotoxins show potent antitumor effects in vitro and in a disseminated human neuroblastoma severe combined immunodeficiency mouse model.	Cancer Res 1994, 54: 6186
Gottschling S, Längler A, Tautz C, Graf N	Complementary and alternative medicine in pediatric oncology.	Klinische Pädiatrie 2006, 218: 157
For many families of pediatric cancer patients the use of complementary and alternative medicine (CAM) is an accepted adjunct to conventional therapy, even if data regarding effects and risks are scarse. This report provides information about the prevalence of CAM use and reasons for CAM use among pediatric cancer patients. Frequently used CAM like nutrition (incl. diets and vitamins), homeopathy, anthroposophic medicine, phytotherapy, and acupuncture are highlighted, as were CAM bearing a special risk for their users. Physicians need to be more aware that a substantial percentage of their patients may use CAM without telling them for different reasons. Physicians need to be open-minded and should discuss CAM with parents. A differentiation between potentially useful and potentially dangerous CAM is necessary aiming at minimising the risks for CAM users.
Gotta J, Bielack S, Hecker-Nolting S, Sorg B, Kevric M, Salzmann-Manrique E, Klingebiel T	When Your Ankle Becomes a Knee - Long-Term Functional Outcome and Quality of Life with a Rotationplasty after Resection of Malignant Limb Tumors.	Klinische Padiatrie 2022, 234: 154
Increasing numbers of patients surviving malignant bone tumors around the knee joint have led to an increasing importance to investigate long-term results. This study assessed the long-term results of rotationplasty after resection of malignant bone tumors regarding functional outcome and quality of life to allow better comparison with other treatment options in bone cancer treatment.
Gotta J, Bochennek K, Klingebiel T, Bielack S, Wild PJ, Demes MC, Gradhand E	Metachronous Osteosarcoma, A Differential Diagnosis to be Considered in Children With Osteosarcoma: A Review of Literature and a Case From Our Center.	Journal of pediatric hematology/oncology 2023, 45: 105
Metachronous osteosarcomas (MOS) are currently defined as tumors that arise in a way and site unusual for typical metastasis. In this article, we reviewed the recent literature on the occurrence of metachronous osteosarcoma and presented a case from our center. Our patient, a 10-year-old girl, presented with metachronous osteoblastic osteosarcoma of the left distal femur ∼5 years after the successful treatment for osteosarcoma of the right distal femur. Even after several relapses, complete remission (CR) was achieved after the first osteosarcoma and after the metachronous osteosarcoma. The literature research revealed that metachronous osteosarcoma occurs in 3.4 to 5.4% of osteosarcoma patients. The time interval between the diagnosis of the initial osteosarcoma and the metachronous tumor ranged from 0.2 to 14.3 years (median 2.5 y). MOS appears to have differences in localization and metastatic spread, as well as a different survival pattern compared with primary osteosarcoma and osteosarcoma recurrence. Survival (median 4.3 y, range 0 to 24.6 y) appears to be associated with the time interval to diagnosis of MOS. In particular, early MOS (<24 mo after primary diagnosis) seem to have a poorer prognosis. Therefore, the occurrence of MOS at oncological unusual sites should be considered as a differential diagnosis in osteosarcoma survivors.
Goumnerova L	Results of stereotactic radiosurgery in the management of recurrent ependymoma.	Proceedings VIIth Annual Symposium Pediatric Neurooncology, Abstract 30 Washington 1996
Gozzelino R, Arosio P	Iron Homeostasis in Health and Disease.	International journal of molecular sciences 2016 Jan 20; 17
Graf N, Winkler K, Betlemovic M, Fuchs N, Bode U	Methotrexate pharmacokinetics and prognosis in osteosarcoma.	J Clin Oncol 1994, 12: 1443
Graf N	Wilms' tumor.	Schweiz Rundsch Med Prax 1996, 85: 753
Graf N, Weirich A	Wilms' tumor - the State of the Art.	Onkologie 1996, 19: 36
Graf N, Weirich A, de Kraker J	Staging problems in the pre-operative chemotherapy of Wilms' tumour.	Br J Urol 1996, 78: 479
Graf N	Nephroblastom (Wilmstumor).	Qualitätssicherung in der Onkologie: Diagnostische und therapeutische Standards in der Pädiatrischen Onkologie 1997
Graf N	Der Wilstumor - State of the art.	Monatsschr Kinderheilkd 1999
Graf N, Zoubek A, Niggli F, Weirich A, Aliani S, Bürger D, Harms D, Flentje M, Pötter R, Zieger B, Ludwig R	Tumor volume and prognosis in patients with localized unilateral nephroblastoma treated preoperatively.	Med Pediatr Oncol 1999, 33
Graf N, Zoubek A, Weirich A, Ludwig R	Erste Ergebnisse der Nephroblastomstudie SIOP 93-01/GPOH und Darstellung einer Nachfolgestudie.	Monatsschr Kinderheilkd 1999
Graubner U, Boos J, Creutzig U, Dörffel W, Lakomek M, Niemeyer C, Schrappe M, Spaar H, Belohradsky B	Die antiinfektiöse Prophylaxe in der Pädiatrischen Onkologie.	Klinische Pädiatrie 1999, 211
Graf N, Tournade M, de Kraker J	The role of preoperative chemotherapy in the management of Wilms' tumor. The SIOP studies. International Society of Pediatric Oncology.	Urol Clin North Am 2000, 27: 443
Gray S, Eriksson T, Ekstrom C, Holm S, von Schweinitz D, Kogner P, Sandstedt B, Pietsch T, Ekstrom T	Altered expression of members of the IGF-axis in hepatoblastomas.	Br J Cancer 2000, 82: 1561
Gray S, Eriksson T, Ekström C, Holm S, Schweinitz D, Kogner P, Sandstedt B, Pietsch T, Ekström T	Decreased expression of insulin-like growth factor binding proteins 1 and 2 in hepatoblastomas; role of the IGF-axis components.	British Journal of Cancer 2000, 82: 1561
Grabenbauer GG, Schuchardt U, Buchfelder M, Rodel CM, Gusek G, Marx M, Doerr HG, Fahlbusch R, Huk WJ, Wenzel D, Sauer R	Radiation therapy of optico-hypothalamic gliomas (OHG)--radiographic response, vision and late toxicity.	Radiother Oncol 2000, 54: 239-45.
Graubner UB	Antiviral prophylaxis.	Klin Pädiatr 2001, 213 Suppl 1:A69
Graubner UB, Liese J, Belohradsky BH	Vaccination.	Klin Pädiatr 2001 213 Suppl 1:A77
Graf Einsiedel H, Taube T, Hartmann R, Wellmann S, Seifert G, Henze G, Seeger K	Deletion analysis of p16(INKa) and p15(INKb) in relapsed childhood acute lymphoblastic leukemia.	Blood 2002, 99: 4629
Graf N, Reinhard H	Wilms tumors. Diagnosis and therapy.	Urologe A 2003, 42:W391-W407
Graf N, Semler O, Reinhard H	Prognosis of Wilm's tumor in the course of the SIOP trials and studies.	Urologe A 2004, 43: 421
Graf N	Osteosarkome.	in: Gutjahr P (Hrsg.): Krebs bei Kindern und Jugendlichen Deutscher Ärzte-Verlag, 5. Aufl. 2004, 473
Graf N, Rübe C, Gessler M	Nierentumoren, in: Gadner H, Gaedicke G, Niemeyer CH, Ritter J (Hrsg.): Pädiatrische Hämatologie und Onkologie.	Springer-Verlag 2006, 847
Graubner UB, Porzig S, Jorch N, Kolb R, Wessalowski R, Escherich G, Janka GE	Impact of reduction of therapy on infectious complications in childhood acute lymphoblastic leukemia.	Pediatric blood & cancer 2008, 50: 259
BACKGROUND: Infections are a major cause of morbidity and mortality in childhood acute lymphoblastic leukemia (ALL) and only limited information is available on infectious complications. PATIENTS AND METHODS: We investigated infectious complications in 293 children during different treatment phases of the multicenter protocol COALL-06-97. We also evaluated whether therapy reduction in prognostically good risk patients receiving either the low risk or high risk treatment arm would lead to fewer infectious complications. RESULTS: Thirty of 293 patients had no infections; 263 patients had 682 infectious complications (median 2, range 1-9), five of them lethal. Two thirds of the infections occurred during periods of neutropenia. The most frequent infectious episodes were fever of unknown origin (FUO): 483/682 (70.8%), microbiologically documented infections (MDI): 100/682 (14.6%), (61 gram-positive, 36 gram-negative, 3 fungal isolates), and clinically documented infections (CDI): 99/682 (14.5%). With standard reinduction, 44% low risk and 57% high risk patients had infections versus 26% low risk and 38% high risk patients with reduced reinduction therapy (P < 0.01). CONCLUSIONS: Most patients treated with intensive combination therapy for ALL experience one to several serious infections during treatment. The wide range in number of infectious episodes and the lack of infections in a small subset of patients in spite of uniform treatment suggest genetic as well as possibly environmental factors to have a role. Moderate reduction of chemotherapy may significantly reduce the rate of infectious episodes.
Grantzow R, Schmittenbecher P, Cremer H, Höger P, Rössler J, Hamm H, Hohenleutner U	Hemangiomas in infancy and childhood. S 2k Guideline of the German Society of Dermatology with the working group Pediatric Dermatology together with the German Society for Pediatric Surgery and the German Society for Pediatric Medicine.	Journal of the German Society of Dermatology 2008, 6: 324
Grabow D, Spix C, Blettner M, Kaatsch P	Strategy for long-term surveillance at the German Childhood Cancer Registry - an update.	Klin padiatr 2011, 223: 159
BACKGROUND: The objective of this paper is to provide information about the quality (e.g. completeness, response) of long-term surveillance in German paediatric oncology and haematology based on the structures implemented by the German Childhood Cancer Registry (GCCR). METHODS: The GCCR contacts parents or patients to collect and update information on a minimal set of follow-up health status data (e.g. late relapses, subsequent neoplasms, current address) and exchanges this information regularly with the appropriate clinical trials. RESULTS: Between 2006 and 2010, GCCR approached a total of about 20,000 patients (contact at the age of 16 years, inquiry concerning the health status) in the context of long-term surveillance. 11,000 addresses of former patients had to be researched via municipal registrar's offices. The response rates ranged from 56% to 68%, the research in municipal offices provided 93-96% valid addresses. Of 46,115 patients diagnosed between 1980 and 2009, 25,283 are in long-term surveillance in 2010. DISCUSSION: Long-term surveillance requires considerable logistic effort at GCCR and requires that thousands of letters be mailed each year in order to ensure regularly updated information. Long-term surveillance is indispensable for a better understanding of late effects, subsequent neoplasms and quality of life of former childhood cancer patients.
Grabow D, Lacher C, Kaatsch P	Former childhood cancer patients need a competent help desk.	Klin padiatr 2011, 223: 187
Grandchamp B, Hetet G, Kannengiesser C, Oudin C, Beaumont C, Rodrigues-Ferreira S, Amson R, Telerman A, Nielsen P, Kohne E, Balser C, Heimpel H	A novel type of congenital hypochromic anemia associated with a nonsense mutation in the STEAP3/TSAP6 gene.	Blood 2011, 118: 6660
STEAP3/TSAP6 encodes a ferrireductase that is involved in the acquisition of iron by developing erythroblasts and steap3/tsap6 null-mice display severe microcytic anemia. We report a family in which 3 siblings born to healthy parents display transfusion-dependent hypochromic anemia. A nonsense STEAP3/TSAP6 was identified in the siblings at the heterozygous state. This mutation was inherited from their father while no mutation was found in their mother. A large variability of expression was found between normal alleles in a control population, confirming a previous report that STEAP3/TSAPS6 is an expressed quantitative trait locus (e-QTL). Determination of the relative allele expression showed that the
Grace RF, Long M, Kalish LA, Neufeld EJ	Applicability of 2009 international consensus terminology and criteria for immune thrombocytopenia to a clinical pediatric population.	Pediatric blood & cancer 2012, 58: 216
Since pediatric immune thrombocytopenia (ITP) is relatively infrequent, comparisons among clinical studies are critical but have previously been limited by differences in terminology. In 2009, an international working group (IWG) developed consensus criteria to enhance comparability in future studies in adults and children.
Grace RF, Bennett CM, Ritchey AK, Jeng M, Thornburg CD, Lambert MP, Neier M, Recht M, Kumar M, Blanchette V, Klaassen RJ, Buchanan GR, Kurth MH, Nugent DJ, Thompson AA, Stine K, Kalish LA, Neufeld EJ	Response to steroids predicts response to rituximab in pediatric chronic immune thrombocytopenia.	Pediatric blood & cancer 2012, 58: 221
Treatment choice in pediatric immune thrombocytopenia (ITP) is arbitrary, because few studies are powered to identify predictors of therapy response. Increasingly, rituximab is becoming a treatment of choice in those refractory to other therapies.
Graf N, Furtwaengler R	Preoperative chemotherapy and local stage III in nephroblastoma.	Translational Pediatrics 2014, 3
The evolution of Nephroblastoma (WT) treatment over the last decades has been one major success around the world. Despite pursuing different upfront treatment approaches the Children’s Oncology Group (COG, former National Wilms Tumor Study Group, NWTSG) and the International Society of Paediatric Oncology’s Renal Tumor Study Group (SIOP-RTSG) show the same outcome. Treatment starts with preoperative chemotherapy in SIOP-RTSG compared to initial surgery in COG. Response to chemotherapy can be used as a stratification parameter. This allows treating patients with blastemal subtype more aggressively resulting in a better event free survival (EFS). Moreover the percentage of patients with local stage III is less in SIOP-RTSG than in COG studies. Lymph node involvement, in NWTS 5 together with residual microscopic disease, results in a lower EFS in both study groups. But overall survival (OS) is not different comparing patients with or without positive lymph nodes (LN). No other reason for stage III has a significant impact on outcome. The role of radiotherapy for local tumor control in stage III is important, but the radiation dose needs to be questioned as 10.8 Gy used in COG is as efficient as 15 Gy in SIOP-RTSG protocols. In addition in part of low income countries radiotherapy can not be given due to a lack of radiation facilities. Nevertheless some patients are cured without irradiation. The analysis of local stage III patients underlines the importance of preoperative chemotherapy and the need for molecular studies to better stratify patients according to their individual risk.
Grainger JD, Locatelli F, Chotsampancharoen T, Donyush E, Pongtanakul B, Komvilaisak P, Sosothikul D, Drelichman G, Sirachainan N, Holzhauer S, Lebedev V, Lemons R, Pospisilova D, Ramenghi U, Bussel JB, Bakshi KK, Iyengar M, Chan GW, Chagin KD, Theodore D, Marcello LM, Bailey CK	Eltrombopag for children with chronic immune thrombocytopenia (PETIT2): a randomised, multicentre, placebo-controlled trial.	Lancet 2015, 386: 1649
The thrombopoietin receptor agonist eltrombopag has been shown to be safe, tolerable, and effective for adults with chronic immune thrombocytopenia. We aimed to investigate the safety and efficacy of eltrombopag for children with chronic immune thrombocytopenia.
Grace RF, Zanella A, Neufeld EJ, Morton DH, Eber S, Yaish H, Glader B	Erythrocyte pyruvate kinase deficiency: 2015 status report.	American journal of hematology 2015, 90: 825
Over the last several decades, our understanding of the genetic variation, pathophysiology, and complications of the hemolytic anemia associated with red cell pyruvate kinase deficiency (PKD) has expanded. Nonetheless, there remain significant gaps in our knowledge with regard to clinical care and monitoring. Treatment remains supportive with phototherapy and/or exchange transfusion in the newborn period, regular or intermittent red cell transfusions in children and adults, and splenectomy to decrease transfusion requirements and/or anemia related symptoms. In this article, we review the clinical diversity of PKD, the current standard of treatment and for supportive care, the complications observed, and future treatment directions.
Graf N	Nephroblastom (Wilms-Tumor).	S1-Leitlinie 025/004 AWMF online 2016
Grace RF, Barcellini W	Management of pyruvate kinase deficiency in children and adults.	Blood 2020, 136: 1241
Pyruvate kinase deficiency (PKD) is an autosomal-recessive enzyme defect of the glycolytic pathway that causes congenital nonspherocytic hemolytic anemia. The diagnosis and management of patients with PKD can be challenging due to difficulties in the diagnostic evaluation and the heterogeneity of clinical manifestations, ranging from fetal hydrops and symptomatic anemia requiring lifelong transfusions to fully compensated hemolysis. Current treatment approaches are supportive and include transfusions, splenectomy, and chelation. Complications, including iron overload, bilirubin gallstones, extramedullary hematopoiesis, pulmonary hypertension, and thrombosis, are related to the chronic hemolytic anemia and its current management and can occur at any age. Disease-modifying therapies in clinical development may decrease symptoms and findings associated with chronic hemolysis and avoid the complications associated with current treatment approaches. As these disease-directed therapies are approved for clinical use, clinicians will need to define the types of symptoms and findings that determine the optimal patients and timing for initiating these therapies. In this article, we highlight disease manifestations, monitoring approaches, strategies for managing complications, and novel therapies in development.
Grainger JD, Kühne T, Hippenmeyer J, Cooper N	Romiplostim in children with newly diagnosed or persistent primary immune thrombocytopenia.	Annals of hematology 2021, Online ahead of print
Immune thrombocytopenia (ITP) is a disease of heterogenous origin characterized by low platelet counts and an increased bleeding tendency. Three disease phases have been described: newly diagnosed (≤ 3 months after diagnosis), persistent (> 3-12 months after diagnosis), and chronic (> 12 months after diagnosis). The majority of children with ITP have short-lived disease and will not need treatment. For children with newly diagnosed ITP, who have increased bleeding symptoms, short courses of steroids are recommended. In children who do not respond to first-line treatment or who become steroid dependent, thrombopoietin receptor agonists (TPO-RAs) are recommended because of their efficacy and safety profiles. In this narrative review, we evaluate the available evidence on the use of the TPO-RA romiplostim to treat children with newly diagnosed or persistent ITP and identify data from five clinical trials, five real-world studies, and a case report. While the data are more limited for children with newly diagnosed ITP than for persistent ITP, the collective body of evidence suggests that romiplostim is efficacious in increasing platelet counts in children with newly diagnosed or persistent ITP and may result in long-lasting treatment-free responses in some patients. Furthermore, romiplostim was found to be well tolerated in the identified studies. Collectively, the data suggest that earlier treatment with romiplostim may help children to avoid the side effects associated with corticosteroid use and reduce the need for subsequent treatment.
Graf N, Bergeron C, Brok J, de Camargo B, Chowdhury T, Furtwängler R, Gessler M, Godzinski J, Pritchard-Jones K, Ramirez-Villar GL, Rübe C, Sandstedt B, Schenk JP, Spreafico F, Sudour-Bonnange H, van Tinteren H, Verschuur A, Vujanic G, van den Heuvel-Eibrink MM	Fifty years of clinical and research studies for childhood renal tumors within the International Society of Pediatric Oncology (SIOP).	Annals of oncology 2021, 32: 1327
Graf M, Interlandi M, Moreno N, Holdhof D, Göbel C, Melcher V, Mertins J, Albert TK, Kastrati D, Alfert A, Holsten T, de Faria F, Meisterernst M, Rossig C, Warmuth-Metz M, Nowak J, Meyer Zu Hörste G, Mayère C, Nef S, Johann P, Frühwald MC, Dugas M, Schüller U, Kerl K	Single-cell transcriptomics identifies potential cells of origin of MYC rhabdoid tumors.	Nature communications 2022, 13: 1544
Rhabdoid tumors (RT) are rare and highly aggressive pediatric neoplasms. Their epigenetically-driven intertumoral heterogeneity is well described; however, the cellular origin of RT remains an enigma. Here, we establish and characterize different genetically engineered mouse models driven under the control of distinct promoters and being active in early progenitor cell types with diverse embryonic onsets. From all models only Sox2-positive progenitor cells give rise to murine RT. Using single-cell analyses, we identify distinct cells of origin for the SHH and MYC subgroups of RT, rooting in early stages of embryogenesis. Intra- and extracranial MYC tumors harbor common genetic programs and potentially originate from fetal primordial germ cells (PGCs). Using PGC specific Smarcb1 knockout mouse models we validate that MYC RT originate from these progenitor cells. We uncover an epigenetic imbalance in MYC tumors compared to PGCs being sustained by epigenetically-driven subpopulations. Importantly, treatments with the DNA demethylating agent decitabine successfully impair tumor growth in vitro and in vivo. In summary, our work sheds light on the origin of RT and supports the clinical relevance of DNA methyltransferase inhibitors against this disease.
Grenzebach J, Schrappe M, Ludwig WD, Parwaresch R, Zimmermann M, Gadner H, Riehm H, Reiter A, BFM-Group	Favorable outcome for children and adolescents with T-cell lymphoblastic lymphoma with an intensive ALL-type therapy without local radiotherapy.	Annals of hematology 2001, 80 Suppl 3:B73
In study NHL-BFM 90 we investigated the efficacy of an ALL-type treatment without local radiotherapy for childhood T-cell lymphoblastic lymphoma (T-LBL). In particular, the prognostic impact of the speed of tumor regression was evaluated. From April 1990 to March 1995, 105 evaluable patients, 1.1-16.4 years of age, with T-LBL were enrolled into study NHL-BFM 90. Patients with stage I and II received an 8-drug induction followed by a consolidation including high-dose-methotrexate (MTX) and maintenance therapy up to a total therapy duration of 24 months. Patients with stage III and IV received an additional reinduction and cranial radiotherapy (CRT) (12 Gy for prophylaxis) between consolidation and maintenance. Residual tumor after completion of induction had to be resected. No local RT was applied. Patients received intensified chemotherapy if tumor regression on day 33 of induction was <70% or when vital residual tumor was present after the induction phase. With a median follow-up of 6.41 years, pEFS at 5 years is 91.4% (SE+/-2.7%). 101 patients were evaluable for the speed of tumor response. Two patients received intensified therapy due to <70% tumor regression on day 33. Of 19 patients with tumor residues after induction, 2 relapsed as compared to 4 of 80 patients with complete tumor regression. Our data demonstrate that, with intensive ALL-type chemotherapy but no local radiotherapy, an event-free survival rate of 90% can be achieved in childhood T-LBL. Providing tumor regression within 5 weeks is sufficient, tumor remnants after induction have weak prognostic impact.
Greaves M	Childhood leukaemia.	BMJ 2002, 324: 283
Greten TF, Manns MP, Reinisch I, Kaatsch P	Hepatocellular carcinoma occurring after successful treatment of childhood cancer with high dose chemotherapy and radiation.	Gut 2005, 54: 732
Green DM, Kawashima T, Stovall M, Leisenring W, Sklar CA, Mertens AC, Donaldson SS, Byrne J, Robison LL	Fertility of female survivors of childhood cancer: a report from the childhood cancer survivor study.	Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2009 Jun 1; 27: 2677
This study was undertaken to determine the effect, if any, of treatment for cancer diagnosed during childhood or adolescence on fertility.
Greve T, Clasen-Linde E, Andersen MT, Andersen MK, Sørensen SD, Rosendahl M, Ralfkiaer E, Andersen CY	Cryopreserved ovarian cortex from patients with leukemia in complete remission contains no apparent viable malignant cells.	Blood 2012, 120: 4311
Some women suffering from leukemia require bone marrow transplantation to be cured. Bone marrow transplantation is associated with a high risk of sterility, and some patients are offered fertility preservation by cryopreservation of the ovarian cortex. Transplantation of the ovarian cortex to women cured of leukemia who became menopausal is currently not performed because of the risk of introducing the disease. In this study, individual pieces of ovarian cortex intended for reimplantation from 25 patients with leukemia were transplanted to each of 25 nude mice for 20 weeks. The ovarian cortex was examined before and after transplantation by histology and immunohistochemistry, and RT-quantitative PCR (in the 7 patients with a known marker). Seventeen patients had the ovarian cortex retrieved when they were in complete remission. Before transplantation, 4 of 7 pieces (2 from patients in complete remission) of ovarian cortex had a positive RT-quantitative PCR. After transplantation, none of the mice revealed any sign of disease, neither in the pieces of ovarian cortex transplanted nor in any of the murine organs evaluated. Thus, the ovaries from patients in complete remission do not appear to contain viable malignant cells contrasting ovarian tissue retrieved before treatment.
Gresele P, Subcommittee on Platelet Physiology of the International Society on Thrombosis and Hemostasis	Diagnosis of inherited platelet function disorders: guidance from the SSC of the ISTH.	Journal of thrombosis and haemostasis : JTH 2015, 13: 314
Grevener K, Haveman LM, Ranft A, van den Berg H, Jung S, Ladenstein R, Klco-Brosius S, Jürgens H, Merks JH, Dirksen U	Management and Outcome of Ewing Sarcoma of the Head and Neck.	Pediatric blood & cancer 2016, 63: 604
Ewing sarcoma (EWS) of the head and neck is rare. Multimodal treatment consists of chemotherapy and local treatment; however, local treatment for EWS of the head and neck is challenging. The first objective was to describe local treatment administered to the patients with localized EWS of the head and neck according to the EURO-E.W.I.N.G.99-trial, and to assess the impact on survival. The second objective was to systematically review the scientific literature available for this topic.
Gresele P, Falcinelli E, Bury L	Inherited platelet function disorders. Diagnostic approach and management.	Hamostaseologie 2016, 36: 265
Greinacher A, Pecci A, Kunishima S, Althaus K, Nurden P, Balduini CL, Bakchoul T	Diagnosis of inherited platelet disorders on a blood smear: a tool to facilitate worldwide diagnosis of platelet disorders.	Journal of thrombosis and haemostasis : JTH 2017, 15: 1511
Greimelmaier K, Calaminus G, Kristiansen G, Vokuhl C, Klapper W	Chromosomal gains of 12p and 1q are not associated with inferior outcome of pediatric and adolescent germ cell tumors.	Pediatric blood & cancer 2019, 66:e27777
Pediatric germ cell tumors (GCT) are rare and very heterogeneous neoplasms that show a high diversity in tumor biology and histology. The clinical behavior cannot be predicted based on morphology or immunohistochemistry. The aim of this study was to investigate a large number of pediatric GCT regarding chromosomal gains of 12p and 1q.
Greinix HT	CAR-T-Zelltherapie: Nachbeobachtung der Patienten und CAR-T-Zell Register.	Sperctrum Onkologie 2019, 06
Grigull L, Beier R, Schrauder A, Kirschner P, Loening L, Jack T, Welte K, Sykora K, Schrappe M	Invasive fungal infections are responsible for one-fifth of the infectious deaths in children with ALL.	Mycoses 2003, 46: 441
Grimer R, Cannon S, Taminiau A, Bielack S, Kempf-Bielack B, Windhager R, Dominkus M, Saeter G, Bauer H, Meller I, Szendroi M, Folleras G, San Julian M, van der Eijken	Osteosarcoma over the age of forty.	Eur J Cancer 2003, 39: 157
Grimbacher, B	J. Schölmerich (Hrsg.): Medizinische Therapie in Klinik und Praxis.	Springer Verlag 2003
Grimer RJ, Bielack S, Flege S, Cannon SR, Foleras G, Andreeff I, Sokolov T, Taminiau A, Dominkus M, San-Julian M, Kollender Y, Gosheger G, European Musculo Skeletal Oncology Society	Periosteal osteosarcoma--a European review of outcome.	European journal of cancer (Oxford, England : 1990) 2005, 41: 2806
Periosteal osteosarcoma is a rare primary malignant bone tumour. Treatment is by surgical excision, but controversy remains about the value of chemotherapy. The members of the European Musculo Skeletal Oncology Society (EMSOS) collaborated to produce a dataset of 119 patients. The predominant site for the tumour was the femur, followed by the tibia. All but 2 patients underwent surgery, with 9 requiring amputation and the others having limb salvage. A total of 81 patients had chemotherapy, of whom 50 had neoadjuvant chemotherapy. There was no standard chemotherapy regime, but all patients receiving chemotherapy were given doxorubicin combined with at least one other agent. The overall survival was 89% at 5 years and 83% at 10 years. Eight patients developed local recurrence, of whom 5 died. Survival was related to appearance of local recurrence (P < 0.0001) but no other single factor. The use of chemotherapy was not shown to be a prognostic factor, but was used in two-thirds of the patients in this study.
Grois N, Flucher-Wolfram B, Heitger A, Mostbeck G, Hofmann J, Gadner H	Diabetes insipidus in Langerhans cell histiocytosis.	Med Pediatr Oncol 1995, 24: 248
Grois N, Favara B, Mostbeck G, Prayer D	Central nervous system disease in Langerhans cell histiocytosis.	Hematol Oncol Clin North Am 1998, 12: 287
Groll A, Ritter J, Müller F	Prevention of fungal infections in children and adolescents with cancer.	Klinische Pädiatrie 2001, 213 Suppl 1:A50-A68
Groll AH, Ritter J, Muller FM	Guidelines for Prevention of Pneumocystis carinii Pneumonitis in Children and Adolescents with Cancer.	Klin Pädiatr 2001, 213 Suppl 1:A38
Groll AH, Ritter J	Diagnosis and management of fungal infections and pneumocystis pneumonitis in pediatric cancer patients.	Klin Pädiatr 2005, 217 Suppl 1:S37
van Grotel M, Meijerink JP, Beverloo HB, Langerak AW, Buys-Gladdines JG, Schneider P, Poulsen TS, den Boer ML, Horstmann M, Kamps WA, Veerman AJ, van Wering ER, van Noesel MM, Pieters R	The outcome of molecular-cytogenetic subgroups in pediatric T-cell acute lymphoblastic leukemia: a retrospective study of patients treated according to DCOG or COALL protocols.	Haematologica 2006, 91: 1212
BACKGROUND AND OBJECTIVES: Subgroups of T-cell acute lymphoblastic leukemia (T-ALL), defined according to recurrent cytogenetic aberrations, may have different prognoses. The aim of this study was to determine the prognostic relevance of molecular-cytogenetic abnormalities in pediatric patients using quantitative real-time polymerase chain reaction and fluorescence in situ hybridization. DESIGN AND METHODS: The patients were assigned to TAL1, HOX11/TLX1, HOX11L2/TLX3, or CALM-AF10 subgroups. The cytogenetic subgroups were characterized in relation to immunophenotype and the expression of aberrantly expressed transcription factors. RESULTS: In our cohort study, CALM-AF10 was associated with an immature immunophenotype and poor outcome (p=0.005). HOX11L2 was associated with both immunophenotypically immature cases as well as cases committed to the gammadelta-lineage. HOX11L2 was significantly associated with poor outcome (p=0.01), independently of the expression of CD1 or the presence of NOTCH1 mutations. TAL1 abnormalities were associated with alphabeta-lineage commitment, and tended to be associated with a good outcome. Cells in HOX11 cases resembled early CD1-positive cortical thymocytes without expression of Cytbeta and TCR molecules. In relation to the expression of early T-cell transcription factors, high TAL1 levels were found in immunophenotypically-advanced cases, whereas high LYL1 levels were found in immature subgroups. INTERPRETATION AND CONCLUSIONS: The reported outcomes for HOX11L2-rearranged T-ALL cases are conflicting; the prognostic impact may depend on the therapy given. In our cohort, this cytogenetic aberration was associated with a poor outcome. Our data on CALM-AF10 rearranged T-ALL, albeit based on only three patients, suggest that this type of leukemia is associated with a poor outcome.
Grotzer MA, von Hoff K, von Bueren AO, Shalaby T, Hartmann W, Warmuth-Metz M, Emser A, Kortmann RD, Kuehl J, Pietsch T, Rutkowski S	Which clinical and biological tumor markers proved predictive in the prospective multicenter trial HIT'91--implications for investigating childhood medulloblastoma.	Klinische Padiatrie 2007, 219: 312
BACKGROUND: Most recent studies analyzing candidate biological prognostic factors in childhood medulloblastoma (MB) are limited by small patient numbers due to dependence on fresh-frozen tumor material. By contrast, large archives of formalin-fixed, paraffin-embedded MB samples exist from homogeneously treated patients. PATIENTS AND METHODS: We have optimized RNA and DNA isolation from formalin-fixed paraffin-embedded MB samples. We then analyzed archived tumor samples from well-documented patients treated within the prospective randomized multicenter trial HIT'91 for DNA amplification of c-myc and N-myc, and mRNA expression of c-myc and trkC. RESULTS: TrkC and c-myc mRNA expression were identified as independent prognostic factors by multivariate analysis. Three risk groups were identified: 1) Favorable risk group: All 8 patients (2 metastatic) with elevated trkC and reduced c-myc mRNA expression (compared to levels of human cerebellum) remained relapse-free (7-year EFS 100%). 2) Poor risk group: 10 of 15 patients with metastatic disease and high c-myc and low trkC mRNA expression relapsed (7-year EFS 33%). 3) Intermediate risk group: The 7-year EFS of the remaining 78 patients was 65%. CONCLUSIONS: While the collection of fresh-frozen tumor samples is remaining a major challenge in large clinical trials, routinely processed paraffin-embedded tissue samples can be used to quantitate biological prognostic factors on the DNA and RNA level. Upon prospective validation of cut-off levels, this may lead to better risk-based stratification systems for children with medulloblastoma.
Grotegut S, Kappler R, Tarimoradi S, Lehembre F, Christofori G, Von Schweinitz D	Hepatocyte growth factor protects hepatoblastoma cells from chemotherapy-induced apoptosis by AKT activation.	International journal of oncology 2010, 36: 1261
Hepatocyte growth factor/scatter factor (HGF) is a ubiquitously expressed molecule that elicits pleiotropic functions on epithelial cells, including mitogenic, motogenic, differentiating, angiogenic and morphogenic effects. In hepatoblastoma (HB), post-operative residual tumor growth and tumor recurrences are often associated with markedly elevated serum levels of HGF, suggesting a link between this molecule and tumor malignancy. Here, we demonstrate that HGF has no impact on overall cell viability and proliferation of HB cells, although signal transduction occurs downstream of HGF, such as c-Met phosphorylation, activation of phosphoinositide 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK)/ERK-1/2 signaling. Instead of being mitogenic, HGF confers anti-apoptotic properties upon serum starvation and moreover protects HB cells against strong apoptotic inducers such as cisplatin and camptothecin, thereby contributing to chemotherapeutic resistance. This effect is mainly dependent on the PI3K/AKT signaling pathway, since inhibition by wortmannin resulted in abrogation of HGF-mediated survival, whereas inhibition of the MAPK pathway had no effect. Together, these findings highlight the importance of HGF in tumor cell survival and suggest that HGF and its cognate receptor c-Met should be considered as a candidate for combined therapeutic strategies of advanced pediatric liver tumors.
Groll AH, Castagnola E, Cesaro S, Dalle JH, Engelhard D, Hope W, Roilides E, Styczynski J, Warris A, Lehrnbecher T, on behalf of the Fourth European Conference on Infections in Leukaemia, a joint venture of the Infectious Diseases Working Party of the European Group for Blood Marrow Transplantation (EBMT-IDWP),the Infectious Diseases Group of the European Organisation for Research and Treatment of Cancer (EORTC-IDG),the International Immunocompromised Host Society (ICHS),the European Leukaemia Net (ELN)	Fourth European Conference on Infections in Leukaemia (ECIL-4): guidelines for diagnosis, prevention, and treatment of invasive fungal diseases in paediatric patients with cancer or allogeneic haemopoietic stem-cell transplantation.	The lancet oncology 2014, 15:e327-e340
Invasive opportunistic fungal diseases (IFDs) are important causes of morbidity and mortality in paediatric patients with cancer and those who have had an allogeneic haemopoietic stem-cell transplantation (HSCT). Apart from differences in underlying disorders and comorbidities relative to those of adults, IFDs in infants, children, and adolescents are unique with respect to their epidemiology, the usefulness of diagnostic methods, the pharmacology and dosing of antifungal agents, and the absence of interventional phase 3 clinical trials for guidance of evidence-based decisions. To better define the state of knowledge on IFDs in paediatric patients with cancer and allogeneic HSCT and to improve IFD diagnosis, prevention, and management, the Fourth European Conference on Infections in Leukaemia (ECIL-4) in 2011 convened a group that reviewed the scientific literature on IFDs and graded the available quality of evidence according to the Infectious Diseases Society of America grading system. The final considerations and recommendations of the group are summarised in this manuscript.
Groebner SN, Worst BC, Weischenfeldt J, Buchhalter I, Kleinheinz K, Rudneva VA, Johann PD, Balasubramanian GP, Segura-Wang M, Brabetz S, Bender S, Hutter B, Sturm D, Pfaff E, Huebschmann D, Zipprich G, Heinold M, Eils J, Lawerenz C, Erkek S, Lambo S, Waszak S, Blattmann C, Borkhardt A, Kuhlen M, Eggert A, Fulda S, Gessler M, Wegert J, Kappler R, Baumhoer D, Burdach S, Kirschner-Schwabe R, Kontny U, Kulozik AE, Lohmann D, Hettmer S, Eckert C, Bielack S, Nathrath M, Niemeyer C, Richter GH, Schulte J, Siebert R, Westermann F, Molenaar JJ, Vassal G, Witt H, ICGC PedBrain-Seq Project,ICGC MMML-Seq Project,Burkhardt B, Kratz CP, Witt O, van Tilburg CM, Kramm CM, Fleischhack G, Dirksen U, Rutkowski S, Fruehwald M, von Hoff K, Wolf S, Klingebiel T, Koscielniak E, Landgraf P, Koster J, Resnick AC, Zhang J, Liu Y, Zhou X, Waanders AJ, Zwijnenburg DA, Raman P, Brors B, Weber UD, Northcott PA, Pajtler KW, Kool M, Piro RM, Korbel JO, Schlesner M, Eils R, Jones DTW, Lichter P, Chavez L, Zapatka M, Pfister SM	The landscape of genomic alterations across childhood cancers.	Nature 2018 Mar 15; 555: 321
Groeneveld-Krentz S, Schroeder MP, Reiter M, Pogodzinski MJ, Pimentel-Gutierrez HJ, Vagkopoulou R, Hof J, Chen-Santel C, Nebral K, Bradtke J, Tuerkmen S, Baldus CD, Gattenloehner S, Haas OA, von Stackelberg A, Karawajew L, Eckert C, Kirschner-Schwabe R	Aneuploidy in children with relapsed B-cell precursor acute lymphoblastic leukaemia: clinical importance of detecting a hypodiploid origin of relapse.	British journal of haematology 2019, 185: 266
Aneuploidy is common in paediatric B-cell precursor acute lymphoblastic leukaemia (ALL). Specific subgroups, such as high hyperdiploidy (>50 chromosomes or DNA Index ≥1·16) and hypodiploidy (<45 chromosomes), predict outcome of patients after primary treatment. Whether aneuploidy has a prognostic value for relapsed disease is yet to be determined. Using DNA index and centromere screening by multiplex ligation-dependent probe amplification, we investigated aneuploidy in 413 children treated for first relapse of B-cell precursor ALL according to the ALL-REZ BFM 2002 protocol. Ten-year event-free survival of patients with high hyperdiploid relapses approached 70%, whereas it was only 40% in low hyperdiploid relapses. Three patients with apparent hyperdiploid relapse had TP53 mutations. In these cases, array-based allelotyping revealed a hypodiploid origin with absence of the hypodiploid founder clone (masked hypodiploidy). Collectively, patients with evident or masked hypodiploid relapses showed an extremely low event-free survival rate of 9%. Importantly, the current relapse risk stratification did not identify cases with masked hypodiploidy as high-risk patients, due to their favourable clinical presentation. In multivariate analysis, hypodiploidy proved to be an independent prognostic factor. This finding supports stratification of relapses with hypodiploid origin into high-risk arms in future trials or allocation of patients to alternative treatment approaches.
Groenendijk A, Spreafico F, de Krijger RR, Drost J, Brok J, Perotti D, van Tinteren H, Venkatramani R, Godziński J, Rübe C, Geller JI, Graf N, van den Heuvel-Eibrink MM, Mavinkurve-Groothuis AMC	Prognostic Factors for Wilms Tumor Recurrence: A Review of the Literature.	Cancers 2021, 13
In high-income countries, the overall survival of children with Wilms tumors (WT) is ~90%. However, overall, 15% of patients experience tumor recurrence. The adverse prognostic factors currently used for risk stratification (advanced stage, high risk histology, and combined loss of heterozygosity at 1p and 16q in chemotherapy-naïve WTs) are present in only one third of these cases, and the significance of these factors is prone to change with advancing knowledge and improved treatment regimens. Therefore, we present a comprehensive, updated overview of the published prognostic variables for WT recurrence, ranging from patient-, tumor- and treatment-related characteristics to geographic and socioeconomic factors. Improved first-line treatment regimens based on clinicopathological characteristics and advancing knowledge on copy number variations unveil the importance of further investigating the significance of biological markers for WT recurrence in international collaborations.
Groenendijk A, van Tinteren H, Jiang Y, de Krijger RR, Vujanic GM, Godzinski J, Rübe C, Schenk JP, Morosi C, Pritchard-Jones K, Al-Saadi R, Vaidya SJ, Verschuur AC, Ramírez-Villar GL, Graf N, de Camargo B, Drost J, Perotti D, van den Heuvel-Eibrink MM, Brok J, Spreafico F, Mavinkurve-Groothuis AMC	Outcome of SIOP patients with low- or intermediate-risk Wilms tumour relapsing after initial vincristine and actinomycin-D therapy only - the SIOP 93-01 and 2001 protocols.	European journal of cancer 2022, 163: 88
Society of International Pediatric Oncology - Renal Tumor Study Group (SIOP-RTSG) treatment recommendations for relapsed Wilms tumour (WT) are stratified by the intensity of first-line treatment. To explore the evidence for the treatment of patients relapsing after vincristine and actinomycin-D (VA) treatment for primary WT, we retrospectively evaluated rescue treatment and survival of this patient group.
Grundy RG, Wilne SA, Weston CL, Robinson K, Lashford LS, Ironside J, Cox T, Chong WK, Campbell RH, Bailey CC, Gattamaneni R, Picton S, Thorpe N, Mallucci C, English MW, Punt JA, Walker DA, Ellison DW, Machin D, Children's Cancer and Leukaemia Group (formerly UKCCSG) Brain Tumour Committee	Primary postoperative chemotherapy without radiotherapy for intracranial ependymoma in children: the UKCCSG/SIOP prospective study.	The lancet oncology 2007, 8: 696
BACKGROUND: Over half of childhood intracranial ependymomas occur in children younger than 5 years. As an adjuvant treatment, radiotherapy can be effective, but has the potential to damage the child's developing nervous system at a crucial time-with a resultant reduction in IQ and cognitive impairment, endocrinopathy, and risk of second malignancy. We aimed to assess the role of a primary chemotherapy strategy in avoiding or delaying radiotherapy in children younger than 3 years with intracranial ependymoma. METHODS: Between December, 1992, and April, 2003, we enrolled 89 children with ependymoma who were aged 3 years or younger at diagnosis, of whom nine had metastatic disease on pre-operative imaging. After maximal surgical resection, children received alternating blocks of myelosuppressive and non-myelosuppressive chemotherapy every 14 days for an intended duration of 1 year. Radiotherapy was withheld unless local imaging (ie, from the child's treatment centre) showed progressive disease. FINDINGS: 50 of the 80 patients with non-metastatic disease progressed, 34 of whom were irradiated for progression. The 5-year cumulative incidence of freedom from radiotherapy for the 80 non-metastatic patients was 42% (95% CI 32-53). With a median follow-up of 6 years (range 1.5-11.3), overall survival for the non-metastatic patients at 3 years was 79.3% (95% CI 68.5-86.8) and at 5 years 63.4% (51.2-73.4). The corresponding values for event-free survival were 47.6% (36.2-58.1) and 41.8% (30.7-52.6). There was no significant difference in event-free or overall survival between complete and incomplete surgical resection, nor did survival differ according to histological grade, age at diagnosis, or site of disease. In 47 of 59 (80%) patients who progressed, relapse resulted from local control only. The median time to progression for the 59 patients who progressed was 1.6 years (range 0.1-10.2 years). The median age at irradiation of the whole group was 3.6 years (range 1.5-11.9). For the 80 non-metastatic patients, the 23 who achieved the highest relative dose intensity of chemotherapy had the highest post-chemotherapy 5-year overall survival of 76% (95% CI 46.6-91.2), compared with 52% (33.3-68.1) for the 32 patients who achieved the lowest relative dose intensity of chemotherapy. INTERPRETATION: This protocol avoided or delayed radiotherapy in a substantial proportion of children younger than 3 years without compromising survival. These results suggest, therefore, that primary chemotherapy strategies have an important role in the treatment of very young children with intracranial ependymoma.
Grünewald TG, Bernard V, Gilardi-Hebenstreit P, Raynal V, Surdez D, Aynaud MM, Mirabeau O, Cidre-Aranaz F, Tirode F, Zaidi S, Perot G, Jonker AH, Lucchesi C, Le Deley M, Oberlin O, Marec-Bérard P, Véron AS, Reynaud S, Lapouble E, Boeva V, Rio Frio T, Alonso J, Bhatia S, Pierron G, Cancel-Tassin G, Cussenot O, Cox DG, Morton LM, Machiela MJ, Chanock SJ, Charnay P, Delattre O	Chimeric EWSR1-FLI1 regulates the Ewing sarcoma susceptibility gene EGR2 via a GGAA microsatellite.	Nat Genet 2015, 47: 1073
Deciphering the ways in which somatic mutations and germline susceptibility variants cooperate to promote cancer is challenging. Ewing sarcoma is characterized by fusions between EWSR1 and members of the ETS gene family, usually EWSR1-FLI1, leading to the generation of oncogenic transcription factors that bind DNA at GGAA motifs. A recent genome-wide association study identified susceptibility variants near EGR2. Here we found that EGR2 knockdown inhibited proliferation, clonogenicity and spheroidal growth in vitro and induced regression of Ewing sarcoma xenografts. Targeted germline deep sequencing of the EGR2 locus in affected subjects and controls identified 291 Ewing-associated SNPs. At rs79965208, the A risk allele connected adjacent GGAA repeats by converting an interspaced GGAT motif into a GGAA motif, thereby increasing the number of consecutive GGAA motifs and thus the EWSR1-FLI1-dependent enhancer activity of this sequence, with epigenetic characteristics of an active regulatory element. EWSR1-FLI1 preferentially bound to the A risk allele, which increased global and allele-specific EGR2 expression. Collectively, our findings establish cooperation between a dominant oncogene and a susceptibility variant that regulates a major driver of Ewing sarcomagenesis.
Grunt S, Mazenauer L, Buerki SE, Boltshauser E, Mori AC, Datta AN, Fluss J, Mercati D, Keller E, Maier O, Poloni C, Ramelli GP, Schmitt-Mechelke T, Steinlin M	Incidence and outcomes of symptomatic neonatal arterial ischemic stroke.	Pediatrics 2015, 135:e1220
Grueneberg I, Baust K, Calaminus G, Creutzig U	Nachsorgeangebote online.	Wir 2017, 1: 22
Das Internetportal www.kinderkrebsinfo.de/nachsorgeangebote bietet zahlreiche neue Informationsmöglichkeiten.
Gruenewald TGP, Cidre-Aranaz F, Surdez D, Tomazou EM, de Álava E,Kovar H, Sorensen PH, Delattre O, Dirksen U	Ewing sarcoma.	Nature reviews. Disease primers 2018 Jul 5; 4: 5
Grümme L, Biewald E, Reschke M, Fischhuber K, Hanbücken A, Schlüter S, Müller B, Kiefer T, Göricke S, Geismar D, Ryl T, Sirin S, Wieland R, Timmermann B, Lohmann D, Ebinger M, Brecht IB, Schönberger S, Schwab C, Eggert A, Süsskind D, Ritter-Sovinz P, Bechrakis NE, Ketteler P	Comparing efficacy and side effects of two systemic chemotherapy regimens for eye-preserving therapy in children with retinoblastoma.	Pediatric blood & cancer 2022, 69:e29362
Background: Eye-preserving therapy in retinoblastoma comprises systemic chemotherapy, but studies analyzing the efficacy of different chemotherapy regimens are scarce. Methods: The efficacy and side effects of two different eye-preserving chemotherapy regimens containing either vincristine, etoposide, and carboplatin (VEC) or cyclophosphamide, vincristine, etoposide, and carboplatin (CyVEC) were compared in a prospective non-interventional observational study including children diagnosed with retinoblastoma between 2013 and 2019 in Germany and Austria. Event-free eye survival (EFES) and overall eye survival (OES) of all 164 eyes treated with both regimens and risk factors were investigated. Results: The EFES after VEC (2-year EFES 72.3%) was higher than after CyVEC (2-year EFES 50.4%) (plogrank < .001). The OES did not differ significantly between the two treatment groups (plogrank = .77; 2-year OES VEC: 82.1% vs. CyVEC: 84.8%). Advanced International Classification of Retinoblastoma (ICRB) group was prognostic for a lower EFES (plogrank < .0001; 2-year EFES ICRB A/B/C 71.3% vs. ICRB D/E 43.0%) and OES (plogrank < .0001; 2-year OES ICRB A/B/C 93.1% vs. ICRB D/E 61.5%). The multivariate analysis showed that age at diagnosis older than 12 months and ICRB A/B/C were associated with better EFES. No second malignancies or ototoxicities were reported after a follow-up of median 3.1 years after diagnosis of retinoblastoma (range 0.1-6.9 years). Conclusions: Despite omitting cyclophosphamide, the EFES was higher after VEC chemotherapy that contains higher doses of carboplatin compared to CyVEC. The major risk factor for enucleation was advanced ICRB tumor grouping. Randomized clinical trials on efficacy and side effects of eye-preserving chemotherapy are required to tailor treatment protocols for retinoblastoma patients.
Guardiola P, Socié G, Pasquini R, Dokal I, Ortega JJ, van Weel-Sipman M, Marsh J, Locatelli F, Souillet G, Cahn JY, Ljungman P, Miniero R, Shaw J, Vermylen C, Archimbaud E, Bekassy AN, Krivan G, Di Bartolomeo P, Bacigalupo A, Gluckman E	Allogeneic stem cell transplantation for Fanconi Anaemia. Severe Aplastic Anaemia Working Party of the EBMT and EUFAR. European Group for Blood and Marrow Transplantation.	Bone Marrow Transplant 1998, 21 Suppl 2:S24
Fanconi anaemia is a hereditary disorder characterised by chromosomal breaks increased by cross-linking agents. Bone marrow transplantation is the treatment of choice when a HLA identical sibling donor has been identified. The use of low-dose cyclophosphamide with thoraco-abdominal irradiation for the conditioning regimen of FA patients has lead to a dramatic improvement of survival, with a long-term survival of 75% at our institution. However, if most patients are completely cured of their haematological disease, there is concern about an increased frequency of secondary tumours, mostly head and neck squamous cell carcinomas of poor prognosis. Results of BMT using alternative donors (HLA mismatched related and unrelated donors) have also improved during the last decade. A better selection of the donor via high-resolution techniques for class-II HLA matching, and more recently the use of T cell depleted grafts are probably the main explanations. Despite a short follow-up and the small number of patients analysed, transplants using HLA matched family cord blood give some promising results. On the other hand, first results with unrelated cord blood remind that this approach is clearly an experimental one that has to be evaluated through international registries and prospective studies. New approaches including autologous stem cell transplantations and gene therapy are currently explored.
Guardiola P, Pasquini R, Dokal I, Ortega JJ, van Weel-Sipman M, Marsh JC, Ball SE, Locatelli F, Vermylen C, Skinner R, Ljungman P, Miniero R, Shaw PJ, Souillet G, Michallet M, Bekassy AN, Krivan G, Di Bartolomeo P, Heilmann C, Zanesco L, Cahn JY, Arcese W, Bacigalupo A, Gluckman E	Outcome of 69 allogeneic stem cell transplantations for Fanconi anemia using HLA-matched unrelated donors: a study on behalf of the European Group for Blood and Marrow Transplantation.	Blood 2000, 95: 422
Allogeneic stem cell transplantation is the only treatment that can restore a normal hematopoiesis in Fanconi anemia (FA). In this retrospective multicenter study, we analyzed the results of this approach using HLA-matched unrelated bone marrow donors, and tried to identify covariates predicting the outcome of the transplant. From January 1985 to June 1998, 69 FA patients were transplanted with unrelated HLA-matched donors. Patients' characteristics before and after transplant were provided by the European group blood and marrow transplant registry and were analyzed in collaboration with the European Fanconi Anemia Registry. The 3-year probability of survival was 33%. Extensive malformations, a positive recipient cytomegalovirus serology, the use of androgens before transplant, and female donors were associated with a worse outcome. Primary graft failures were observed more frequently when female donors were used, mainly because the grafts contained lower nucleated cell doses per kilogram of recipient body weight compared with grafts coming from male donors. The probability of grade III-IV acute graft-versus-host disease (GVHD) was 34%. Elevated serum alanine/aspartate transaminases before transplantation; limb, urogenital tract, or nephrologic malformations; and non-T-cell-depleted grafts were predictors of severe acute GVHD. This study shows the dramatic impact of preexisting congenital malformations on the outcome of FA patients transplanted with HLA-matched unrelated donors. If the use of T-cell depletion has led to a dramatic reduction of acute GVHD incidence, no significant outcome improvement was observed with this approach, mainly because of an increased risk of graft failure. (Blood. 2000;95:422-429)
Gualandro SF, Fonseca GH, Yokomizo IK, Gualandro DM, Suganuma LM	Cohort study of adult patients with haemoglobin SC disease: clinical characteristics and predictors of mortality.	British journal of haematology 2015, 125: 3401
Haemoglobin (Hb) SC disease is the second most common subtype of sickle cell disease and is potentially fatal. This study aimed to determine the clinical characteristics, outcome and predictors of mortality in HbSC disease patients, and to compare these findings with patients followed-up in different centres. Clinical, laboratory and outcome data were collected from a cohort of adult patients with HbSC disease followed between 1991 and 2103. Cox regression multivariate analysis was used to determine predictors of mortality. One hundred and fifty-five patients were followed-up over 20 years: 9% died and 70·8% had at least one complication. The most common complications were: painful crises (38·3%), retinopathy (33·8%), cholelithiasis (30·3%), osteonecrosis (24·8%) and sensorineural hearing disorders (9·7%). Frequency of chronic complications was similar in most studies. In multivariate analysis, hearing disorders remained an independent predictor of mortality (Odds Ratio 9·26, 95% confidence interval 1·1-74·8; P = 0·03). It was concluded that patients with HbSC disease receive a late diagnosis and there is remarkable similarity between the studies conducted in different centres around the world. Sensorineural hearing disorders were an independent predictor of mortality, suggesting that it may be useful to implement routine diagnostic screening.
Guckenberger M, Andratschke N, Alheit H, Holy R, Moustakis C, Nestle U, Sauer O, Deutschen Gesellschaft fÃ¼r Radioonkologie (DEGRO)	Definition of stereotactic body radiotherapy: principles and practice for the treatment of stage I non-small cell lung cancer.	Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] 2014, 190: 26
Guckenberger M, Andratschke N	Stereotaktische Bestrahlung: Lokale Tumorkontrolle enorm verbessert.	Dtsch Arztebl 2014, 111: [20]
Guder WK, Hardes J, Nottrott M, Steffen AJ, Dirksen U, Streitbürger A	Pelvic Ewing sarcoma: a retrospective outcome analysis of 104 patients who underwent pelvic tumor resection at a single supra-regional center.	Journal of orthopaedic surgery and research 2020, 15: 534
Local treatment in pelvic Ewing sarcoma (ES) consists of operation, radiation therapy, or a combination of both. Reported outcomes vary depending on the treatment modality performed. It is the objective of this study to analyze surgical outcome and complications as well as oncological outcome and complications of chemo- and radiation therapy in this patient cohort and evaluate prognostic factors.
Guggemos A, Eckert C, Szczepanski T, Hanel C, Taube T, van der, Graf-Einsiedel H, Henze G, Seeger K	Assessment of clonal stability of minimal residual disease targets between 1st and 2nd relapse of childhood precursor B-cell acute lymphoblastic leukemia.	haematologica 2003, 88: 736
Gulden J	Überlebende kindlicher Krebserkrankungen: Gebrechlich wie Senioren.	Dtsch Arztebl 2014, 111: A-1860 / B-1593 / C
Gunther P, Troger J, Graf N, Waag K, Schenk J	MR volumetric analysis of the course of nephroblastomatosis under chemotherapy in childhood.	Pediatr Radiol 2004, 34: 660
Gururangan S, McLaughlin C, Quinn J, Rich J, Reardon D, Halperin EC, Herndon J, Fuchs H, George T, Provenzale J, Watral M, McLendon RE, Friedman A, Friedman HS, Kurtzberg J, Vredenbergh J, Martin PL	High-dose chemotherapy with autologous stem-cell rescue in children and adults with newly diagnosed pineoblastomas.	J Clin Oncol 2003, 21: 2187
PURPOSE: We evaluated the usefulness of a treatment regimen that included high-dose chemotherapy (HDC) with autologous stem-cell rescue (ASCR) in patients with newly diagnosed pineoblastoma (PBL). PATIENTS AND METHODS: Twelve patients with PBL were initially treated with surgery and induction chemotherapy. All but two patients underwent radiotherapy. Subsequently, all patients received HDC using cyclophosphamide (CTX) + melphalan (MEL) or busulfan (Bu) + MEL regimens and ASCR. RESULTS: A total of six children and six adults with median ages of 4.2 (range, 0.3 to 19.8 years) and 23 years (range, 23 to 43.7 years), respectively, were treated according to this strategy. Four patients had metastatic disease confined to the neuraxis. Five of 12 patients (42%) had a complete tumor resection at diagnosis. Ten patients received radiotherapy at median doses of 36.0 and 59.4 Gy to the neuraxis and pineal region, respectively. Eleven patients received HDC with CTX + MEL, and one patient received BU + MEL followed by ASCR. Nine patients are alive with no evidence of disease recurrence at a median of 62 months from diagnosis (range, 28 to 125 months), including three patients with metastatic disease and two infants who did not receive any radiotherapy. Three patients have died of progressive disease at 19, 32, and 37 months from diagnosis, respectively. The actuarial 4-year progression-free and overall survivals are 69% (95% confidence interval [CI], 39% to 99%) and 71% (95% CI, 43% to 99%), respectively. CONCLUSION: The use of HDC in addition to radiotherapy seems to be an effective treatment for patients with newly diagnosed pineoblastoma.
Gutjahr P	Krebs? Mein Kind? Leukämie und bösartige Tumoren bei Kindern.	S. Hirzel Verlag Stuttgart - Leipzig 2000, 53
Gutjahr P	Krebs bei Kindern und Jugendlichen.	Deutscher Ärzte-Verlag Köln 5. Aufl. 2004
Gutjahr P	Tumoren des Zentralnervensystems, in: Gutjahr P (Hrsg.): Krebs bei Kindern und Jugendlichen.	Deutscher Ärzte-Verlag Köln 5. Aufl. 2004, 373
Gutjahr P	Retinoblastome, in: Gutjahr P (Hrsg.): Krebs bei Kindern und Jugendlichen.	Deutscher Ärzte-Verlag Köln 5. Aufl. 2004, 499
Göbel U, Bamberg M, Calaminus G, Gnekow A, Herrmann H, Lenard H, Spaar H, Niethammer D, Kühl J, Harms D	Improved prognosis of intracranial germ cell tumors by intensified therapy.	Klin Pädiatr 1993, 205: 217
Göbel U, Calaminus G, Teske C, Bamberg M, Bokkerink J, Haas R, Holschneider A, Janka-Schaub G, Jürgens H, Mittler U	BEP/VIP in children and adolescents with malignant non-testicular germ cell tumors. A comparison of the results of treatment of therapy studies MAKEI 83/86 and 89P/89.	Klin Pädiatr 1993, 205: 231
Göbel U, Calaminus G, Harms D	Ovarielle Keimzelltumoren bei Kindern und Jugendlichen:Ergebnisse der Studien MAKEI 1983/86 und 89 der Gesellschaft für Pädiatrische Onkologie und Hämatologie (GPOH).	GPOH 1995, 23
Göbel U	Teratome und andere Keimzelltumoren.	Therapie der Krankheiten im Kindes- und Jugendalter 1997, 507
Göbel U, Calaminus G, Haas H	Keimzelltumoren.	Diagnostische und therapeutische Standards in der Pädiatrischen Onkologie 1997, 69
Göbel U, Calaminus G, Haas H	Keimzelltumoren im Kindesalter, in Schmoll, H.-J, Höffken, K, Possinger, K. (Hrsg.).	Kompendium internistischer Onkologie, Berlin, Springer 1997, 2
Göbel U, Calaminus G, Haas R	Keimzelltumoren.	Uroonkologie 1997, 598
Göbel U, Calaminus G, Engert J, Kaatsch P, Gadner H, Bokkerink J, Hass R, Waag K, Blohm M, Dippert S, Teske C, Harms D	Teratomas in infancy and childhood.	Med Pediatr Oncol 1998, 31: 8
Göbel U, Calaminus G, Waag K, Jonat W, Harms D	Extracranial non-testicular teratoma in childhood and adolescents-the German experience.	Germ Cell Tumors 1998,IV: 233
Göbel U, Calaminus G, Haas R	Keimzelltumoren im Kindesalter (Solide Tumoren im Kindesalter).	Kompendium internistischer Onkologie In Schmoll, H -J , Höffken,K , Possinger,K (eds), Berlin, Springer 1999, 2
Göbel U, Schneider D, Calaminus G, Harms D	Tumoren im Kindesalter. Maligne Keimzelltumoren.	Onkologie systematisch (Diagnostik und interdisziplinäre Therapie maligner Tumoren) 1999, 396
Göbel U, Calaminus G, Bamberg M, Engert J, Haas H, Jonat W, Kortmann R, Schneider D, Harms D	Keimzelltumoren bei Kindern und Jugendlichen.	Der Onkologe 2000, 6
Göbel U, Calaminus G, Engert J, Haas R, Jonat W, Harms D	Malignant extracranial non-testicular germ cell tumors (GCTs)-the German experience.	Germ Cell Tumors 2000,IV: 205
Göbel U, Schneider D, Calaminus G, Haas R, Schmidt P, Harms D	Germ-cell tumors in childhood and adolescence. GPOH MAKEI and the MAHO study groups.	Ann Oncol 2000, 11: 263
Göbel U, Schneider D, Calaminus G, Jürgens H, Spaar H, Sternschulte W, Waag K, Harms D	Multimodal treatment of malignant sacrococcygeal germ cell tumors.	J Clin Oncol 2001, 19: 1943
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