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Autor(en)	Titel	Quelle
Aarbakke J, Janka-Schaub G, Elion G	Thiopurine biology and pharmacology.	Trends Pharmacol Sci 1997, 18: 3
Abdollahzadeh M, Hoffman HJ, Blazer SI, Becker LE, Humphreys RP, Drake JM, Rutka JT	Benign cerebellar astrocytoma in childhood: experience at the Hospital for Sick Children 1980-1992.	Childs Nerv Syst 1994, 10: 380
Abdel-Salam GMH, Hellmuth S, Gradhand E, Käseberg S, Winter J, Pabst AS, Eid MM, Thiele H, Nürnberg P, Budde BS, Toliat MR, Brecht IB, Schroeder C, Gschwind A, Ossowski S, Häuser F, Rossmann H, Abdel-Hamid MS, Hegazy I, Mohamed AG, Schneider DT, Bertoli-Avella A, Bauer P, Pearring JN, Pfundt R, Hoischen A, Gilissen C, Strand D, Zechner U, Tashkandi SA, Faqeih EA, Stemmann O, Strand S, Bolz HJ	Biallelic MAD2L1BP (p31comet) mutation is associated with mosaic aneuploidy and juvenile granulosa cell tumors.	JCI insight 2023, 8
MAD2L1BP-encoded p31comet mediates Trip13-dependent disassembly of Mad2- and Rev7-containing complexes and, through this antagonism, promotes timely spindle assembly checkpoint (SAC) silencing, faithful chromosome segregation, insulin signaling, and homology-directed repair (HDR) of DNA double-strand breaks. We identified a homozygous MAD2L1BP nonsense variant, R253, in 2 siblings with microcephaly, epileptic encephalopathy, and juvenile granulosa cell tumors of ovary and testis. Patient-derived cells exhibited high-grade mosaic variegated aneuploidy, slowed-down proliferation, and instability of truncated p31comet mRNA and protein. Corresponding recombinant p31comet was defective in Trip13, Mad2, and Rev7 binding and unable to support SAC silencing or HDR. Furthermore, C-terminal truncation abrogated an identified interaction of p31comet with tp53. Another homozygous truncation, R227, detected in an early-deceased patient with low-level aneuploidy, severe epileptic encephalopathy, and frequent blood glucose elevations, likely corresponds to complete loss of function, as in Mad2l1bp-/- mice. Thus, human mutations of p31comet are linked to aneuploidy and tumor predisposition.
Abele M, Voggel S, Bremensdorfer C, Spix C, Erdmann F, Kuhlen M, Redlich A, Ebinger M, Lang P, Schneider DT, Brecht IB	Incidences and characteristics of primary lung malignancies in childhood in Germany: An analysis of population-based data from German cancer registries.	Pediatric blood & cancer 2022,e2974
Primary lung malignancies are a heterogeneous group of cancers that occur very rarely in childhood. Due to limited knowledge of their epidemiologic and clinical features, these tumors present a challenge to the treating physicians. This study aimed to increase the knowledge about the occurrence of primary lung malignancies in childhood in Germany.
Abele M, Bajčiová V, Wright F, Behjati S, Voggel S, Schneider DT, Mallebranche C, Česen Mazič M, Guillén G, Krawczyk M, Bień E, Roganovic J, Bisogno G, Chiaravalli S, Ferrari A, Brecht IB, Orbach D, Reguerre Y, Virgone C	Primary lung carcinoma in children and adolescents: An analysis of the European Cooperative Study Group on Paediatric Rare Tumours (EXPeRT).	European journal of cancer (Oxford, England : 1990) 2022, 175: 19
Primary lung carcinoma is an exceptionally rare childhood tumour, as per definition of the European Cooperative Study Group on Paediatric Rare Tumours (EXPeRT), with an incidence of 0.1-0.2/1,000,000 per year. Little is known about the clinical characteristics of children with primary lung carcinoma, a gap which this joint analysis of the EXPeRT group aimed to fill.
Abele M, Grabner L, Blessing T, Block A, Agaimy A, Kratz C, Simon T, Calaminus G, Heine S, Corbacioglu S, Christiansen H, Schneider DT, Brecht IB	Epidemiology and Characteristics of Gastric Carcinoma in Childhood-An Analysis of Data from Population-Based and Clinical Cancer Registries.	Cancers 2023, 15
(1) Background: Gastric carcinoma is an exceptionally rare tumor in childhood. Little is known about the etiology, epidemiology, and clinical features of pediatric gastric carcinomas. This analysis aimed to fill this gap by increasing knowledge about the occurrence of gastric carcinoma in childhood. (2) Material and methods: Data from gastric carcinoma cases diagnosed between 2000 and 2017/2018 were retrieved from the Surveillance, Epidemiology, and End Results Program (SEER) and the German Center for Cancer Registry Data. Data from patients <20 years of age were analyzed for patient- and tumor-related characteristics. In addition, clinical data from patients with gastric carcinoma registered in the German Registry for Rare Pediatric Tumors (STEP) were analyzed for diagnostics, therapy, and outcome. (3) Results: Ninety-one cases of gastric carcinoma, mainly in adolescents, were identified in the epidemiologic cancer registries. Among patients with recorded staging data, advanced tumor stages were common (66.7%). Within the follow-up period covered, 63.7% of patients with clinical follow-up data died. Eight pediatric patients with gastric carcinoma were enrolled in the STEP registry, among whom two were patients with hereditary CDH1 mutations and another was a patient with Peutz−Jeghers syndrome. Three patients were found to have distinctly decreased immunoglobulin concentrations. All four patients in whom complete resection was achieved remained in remission. Three of the other four patients died despite multimodal therapy. (4) Conclusions: A combination of Helicobacter pylori infection and tumor predisposition and/or immunodeficiency appears to promote the development of gastric carcinoma in childhood. While patients with localized disease stages have a good chance of achieving durable remission through complete resection, patients with stage IV carcinomas face a dismal prognosis, highlighting the need to develop new strategies such as mutation-guided treatments.
Abele M, Kunstreich M, Lessel L, Seitz G, Vokuhl C, Lapa C, Schneider DT, Brecht IB, Redlich A, Kuhlen M	Bronchial carcinoid tumors in children and adolescents - A report and management considerations from the German MET studies.	Lung cancer 2023, 183: 107320
Bronchial carcinoid tumors (BC) are exceptionally rare in childhood, with an incidence of <0.2/1,000,000 per year. Typical low-grade BCs are distinguished from atypical, intermediate-grade BCs. Little is known about BCs in pediatric patients and management guidelines are missing. In this study, we explored characteristics and outcome of pediatric patients with BC prospectively registered with the Malignant Endocrine Tumor studies.
Abla O, Kutny MA, Testi AM, Feusner JH, Creutzig U, Gregory J Jr, Gibson B, Leverger G, Ribeiro RC, Smith O, Locatelli F, Kaspers G	Management of relapsed and refractory childhood acute promyelocytic leukaemia: recommendations from an international expert panel.	British journal of haematology 2016, 175: 588
Abramson DH, Frank CM	Second nonocular tumors in survivors of bilateral retinoblastoma: a possible age effect on radiation-related risk.	Ophthalmology 1998, 105: 573-9; discussion 579
OBJECTIVE: This study aimed to investigate the relationship in bilateral retinoblastoma survivors between the incidence of second tumors and the age when external beam radiation (EBR) was used. DESIGN: A retrospective analysis of patients diagnosed with retinoblastoma was performed by examining records for background information and treatment information as well as reviewing documentation of patients with second nonocular tumors. Two telephone interviews were conducted for follow-up as well as inquiries directed to tumor registries and state databases. PARTICIPANTS: The original study included 1729 patients treated in New York and Boston; the current study includes only the 1506 patients treated in New York. Of those, 816 patients were diagnosed with bilateral retinoblastoma, had sufficient treatment data to be useful, and survived at least 1 year from diagnosis. MAIN OUTCOME MEASURES: The subjects were observed for evidence of the development of second nonocular tumors. RESULTS: There was a significant decrease in tumor-free survival among patients treated with EBR before the age of 12 months, but no significant difference between the group treated with EBR after the age of 12 months and the group not treated with EBR. For tumors in the field of radiation, patients treated with early EBR showed a significant decrease in tumor-free survival when compared to patients treated with late EBR, with no significant difference between late radiation and no radiation. There were no significant differences between groups for tumors out of the field of radiation. Significant differences attributable to the use of EBR were found only for tumors of the skull and face bones and for tumors of the soft tissue of the head. CONCLUSIONS: The long-term effect of radiation treatment on survivors of bilateral retinoblastoma is to increase the incidence and affect the distribution of second tumors. However, no increased risk is observed for tumors out of the field of radiation among patients who underwent radiation, and the risk for tumors in the field of radiation is heavily dependent on the age at which EBR is given and may be acceptably small to the patient after the age of 12 months.
Achajew A, Brecht IB, Radespiel-Tröger M, Meyer M, Metzler M, Bremensdorfer C, Spix C, Erdmann F, Schneider DT, Abele M	Rare pediatric tumors in Germany - not as rare as expected: a study based on data from the Bavarian Cancer Registry and the German Childhood Cancer Registry.	European journal of pediatrics 2022, 181: 2723
Very rare pediatric tumors (VRTs) pose a challenge for treating physicians as little is known about the best diagnostic assessment and therapeutic decision-making in these malignancies. A large proportion of these cancers occur in adolescence. Therefore, the established structures of pediatric oncology including cancer registration may partly be circumvented. This may lead to an underregistration in clinical cancer registries of yet unclear extent. The aim of this study is to increase the knowledge on the occurrence of VRTs in pediatric patients in Germany. Pseudonymized data of cases recorded in the Bavarian Cancer Registry (BCR) between 2002 and 2014 were retrieved. VRTs according to the definition of the European Cooperative Study Group for Pediatric Rare Tumors were identified using the ICD and ICD-O classification. The numbers of registered patients were compared to those reported to the German Childhood Cancer Registry (GCCR). 6.3% (n = 290) of all malignancies (n = 4615) in the age below 18 years were classified as VRTs. Median age at diagnosis was 15 years (range 0-17 years). The most common tumor types included malignant melanoma, skin carcinoma, and gonadal tumors. During the same period, 49 pediatric patients from Bavaria with matchable VRTs were reported to the GCCR, accounting for 17% of cases reported to the BCR.
Ackermann S, Cartolano M, Hero B, Welte A, Kahlert Y, Roderwieser A, Bartenhagen C, Walter E, Gecht J, Kerschke L, Volland R, Menon R, Heuckmann JM, Gartlgruber M, Hartlieb S, Henrich KO, Okonechnikov K, Altmüller J, Nürnberg P, Lefever S, de Wilde B, Sand F, Ikram F, Rosswog C, Fischer J, Theissen J, Hertwig F, Singhi AD, Simon T, Vogel W, Perner S, Krug B, Schmidt M, Rahmann S, Achter V, Lang U, Vokuhl C, Ortmann M, Büttner R, Eggert A, Speleman F, O'Sullivan RJ, Thomas RK, Berthold F, Vandesompele J, Schramm A, Westermann F, Schulte JH, Peifer M, Fischer M	A mechanistic classification of clinical phenotypes in neuroblastoma.	Science (New York, N.Y.) 2018 Dec 7; 362: 1165
Neuroblastoma is a pediatric tumor of the sympathetic nervous system. Its clinical course ranges from spontaneous tumor regression to fatal progression. To investigate the molecular features of the divergent tumor subtypes, we performed genome sequencing on 416 pretreatment neuroblastomas and assessed telomere maintenance mechanisms in 208 of these tumors. We found that patients whose tumors lacked telomere maintenance mechanisms had an excellent prognosis, whereas the prognosis of patients whose tumors harbored telomere maintenance mechanisms was substantially worse. Survival rates were lowest for neuroblastoma patients whose tumors harbored telomere maintenance mechanisms in combination with RAS and/or p53 pathway mutations. Spontaneous tumor regression occurred both in the presence and absence of these mutations in patients with telomere maintenance-negative tumors. On the basis of these data, we propose a mechanistic classification of neuroblastoma that may benefit the clinical management of patients.
Adams RJ	Prevention of stroke in sickle cell anemia.	The Journal of law, medicine & ethics 2014, 42: 135
The risk of stroke for a child with SCD is many times greater than that of a healthy child without SCD or heart disease. There is a technique that allows the identification of the children with SCD who have high risk even within this relatively high-risk group. And there is a highly effective preventive treatment. While this would on the surface appear to be a straightforward medical decision, it is not. One must weigh the benefits of preventing permanent brain damage against the risks of infection from transfused blood, iron overload, which is the result of the frequent transfusions, and rare transfusion reactions.
Adams RJ, Cox M, Ozark SD, Kanter J, Schulte PJ, Xian Y, Fonarow GC, Smith EE, Schwamm LH	Coexistent Sickle Cell Disease Has No Impact on the Safety or Outcome of Lytic Therapy in Acute Ischemic Stroke: Findings From Get With The Guidelines-Stroke.	Stroke 2017, 48: 686
Abstract BACKGROUND AND PURPOSE: The recommended treatment for ischemic stroke is tPA (tissue-type plasminogen activator). Although sickle cell disease (SCD) represents no known contraindication to tPA, National Heart Lung and Blood Institute of the National Institutes of Health recommended acute exchange transfusion for stroke in SCD, not tPA. Data on safety and outcomes of tPA in patients are needed to guide tPA use in SCD. METHODS: We matched patients from the American Heart Association and American Stroke Association Get With The Guidelines-Stroke registry with SCD to patients without SCD and compared usage, complications, and discharge outcomes after tPA. Multivariable logistic regression models using generalized estimating equations were used to assess outcomes. RESULTS: From 2 016 652 stroke patients admitted to Get With The Guidelines-Stroke sites in the United States, 832 SCD and 3328 non-SCD controls with no differences in admission National Institutes of Health Stroke Scale or blood pressure were identified. Neither the fraction receiving thrombolytic therapy (8.2% for SCD versus 9.4% non-SCD) nor symptomatic intracranial hemorrhage (4.9% of SCD versus 3.2% non-SCD; P=0.4502) was different. There was no difference in a prespecified set of outcome measures for those with SCD compared with controls. CONCLUSIONS: Coexistent SCD had no significant impact on the safety or outcome of thrombolytic therapy in acute ischemic stroke. Although the sample size is relatively small, these data suggest that adults with SCD and acute ischemic stroke should be treated with thrombolysis, if they otherwise qualify. Addition studies, however, should track the intracranial hemorrhage rate and provide information on other SCD-related care such as transfusion.
Adolph JE, Fleischhack G, Mikasch R, Zeller J, Warmuth-Metz M, Bison B, Mynarek M, Rutkowski S, Schüller U, von Hoff K, Obrecht D, Pietsch T, Pfister SM, Pajtler KW, Witt O, Witt H, Kortmann RD, Timmermann B, Krauß J, Frühwald MC, Faldum A, Kwiecien R, Bode U, Tippelt S	Local and systemic therapy of recurrent ependymoma in children and adolescents: short- and long-term results of the E-HIT-REZ 2005 study.	Neuro-oncology 2021, 23: 1012
Survival in recurrent ependymomas in children and adolescents mainly depends on the extent of resection. Studies on repeated radiotherapy and chemotherapy at relapse have shown conflicting results.
Adolph JE, Fleischhack G, Gaab C, Mikasch R, Mynarek M, Rutkowski S, Schüller U, Pfister SM, Pajtler KW, Milde T, Witt O, Bison B, Warmuth-Metz M, Kortmann RD, Dietzsch S, Pietsch T, Timmermann B, Tippelt S, German GPOH HIT-Network	Systemic chemotherapy of pediatric recurrent ependymomas: results from the German HIT-REZ studies.	Journal of neuro-oncology 2021, 155: 193
Survival in recurrent ependymoma (EPN) depends mainly on the extent of resection achieved. When complete resection is not feasible, chemotherapy is often used to extend progression-free and overall survival. However, no consistent effect of chemotherapy on survival has been found in patients with recurrent EPN.
Aerts I, Sastre-Garau X, Savignoni A, Lumbroso-Le Rouic L, Thebaud-Leculée E, Frappaz D, Coze C, Thomas C, Gauthier-Villars M, L'evy-Gabriel C, Brisse HJ, Desjardins L, Doz F	Results of a Multicenter Prospective Study on the Postoperative Treatment of Unilateral Retinoblastoma Following Primary Enucleation.	J Clin Oncol 2013 Mar 4; [Epub ahead of print]
PURPOSEThe objective of this prospective study was to assess overall survival and event-free survival in patients with intraocular unilateral retinoblastoma (Reese-Ellsworth group V) treated by primary enucleation with or without adjuvant therapy depending on histopathologic risk factors. PATIENTS AND METHODSPatients (n = 123) were divided into three groups on the basis of risk factors for extraocular relapse and metastasis assessed on centralized histologic examination of enucleated eyes. Group 1 (n = 70) had minimal or no choroidal involvement and/or prelaminar or no optic nerve involvement and received no adjuvant therapy. Group 2 (n = 52) had massive choroidal involvement and/or intra- or retrolaminar optic nerve involvement and/or anterior segment involvement and received four courses of adjuvant chemotherapy. Group 3 (n = 1) had invasion of the surgical margin of the optic nerve and/or microscopic extrascleral involvement and received six courses of adjuvant chemotherapy with intrathecal thiotepa, consolidation chemotherapy, and autologous stem-cell rescue. Genetic testing was also performed.ResultsMedian follow-up for the 123 patients was 71 months. No disease progression, relapse, or distant metastasis occurred during follow-up. No second malignancies occurred. This requires confirmation with longer follow-up. Secondary bilateralization occurred in two patients with identified RB1 germline mutation. Adjuvant chemotherapy was well tolerated, with limited toxicity. Molecular testing found constitutional RB1 gene mutations in only nine of 100 evaluated patients. CONCLUSIONThe survival rate of 100% was excellent, including 57% of patients who received no adjuvant therapy, suggesting that chemotherapy could be de-escalated in some patients, especially those with massive choroidal involvement.
Agostini A, Cicardi M	Hereditary and acquired C1-inhibitor deficiency: biological and clinical characteristics in 235 patients.	Medicine 1992l; 71: 206-15.
Two hundred and twenty-six patients with inherited C1 inhibitor (C1-INH) deficiency, also known as hereditary angioedema (HAE), have been studied. They belonged to 80 unrelated families, and in 11 of them C1-INH was functionally deficient but antigenically normal (type II HAE). Genetic analysis of type 1 families demonstrated restriction fragment length polymorphisms in 11% and abnormal mRNAs in 25%. In type II families, the site of the mutation appeared to determine the rate of catabolism of the dysfunctional C1-INH and its antigenic plasma levels. Clinical symptoms (subcutaneous and mucous swellings) generally first appeared within the second decade of life. The frequency of symptoms was highly variable from patient to patient, but a few patients remained asymptomatic throughout their lives. Prophylactic treatment with attenuated androgens was administered to 59 patients and was totally effective in 57, without significant side effects. Sixty-seven laryngeal and 15 abdominal attacks were treated with C1-INH plasma concentrate, yielding initial regression of symptoms in 30 to 90 minutes. The acquired deficiency of C1-INH, also known as acquired angioedema, was diagnosed in 9 patients. Eight of them had an autoantibody against C1-INH; the only patient without the autoantibody had associated chronic lymphocytic leukemia. Prophylactic treatment with attenuated androgens was effective in this last patient, while those with the autoantibody against C1-INH benefited from prophylaxis with antifibrinolytic agents. Replacement therapy with C1-INH concentrate was necessary only for patients with autoantibodies and required doses 3 or 4 times higher than those used in HAE
Agrawal AK, Hsu E, Quirolo K, Neumayr LD, Flori HR	Red blood cell transfusion in pediatric patients with severe chronic anemia: How slow is necessary?	Pediatric blood & cancer 2012, 58: 466
Historic practice recommends slow transfusion for children with chronic anemia and hemoglobin less than 5.0 g/dl due to the theoretical risk of transfusion-associated circulatory overload (TACO). In our pediatric intensive care unit (PICU), we have been utilizing a more liberal transfusion practice in patients without underlying cardiopulmonary disease, and a faster transfusion rate appears safe in this population. Rate of transfusion must be based on multiple factors including convenience, timeliness of procedures and transport to an appropriate care facility, risk of alloimmunization and wastage of blood, stress for the family, and need for PICU monitoring. Pediatr Blood Cancer 2012; 58: 466-468. © 2011 Wiley Periodicals, Inc.
Aguilar Martinez P, Angastiniotis M, Eleftheriou A, Gulbis B, Mañú Pereira Mdel M, Petrova-Benedict R, Corrons JL	Haemoglobinopathies in Europe: health & migration policy perspectives.	Orphanet journal of rare diseases 2014, 9: 97
Major haemoglobinopathies (MH), such as thalassaemia syndromes (Thal) and sickle cell disorders (SCD), are genetic defects associated with chronic anaemia and other complications. In Europe, MH are rare diseases (RD) but their prevalence is significantly growing in many countries due to mobility and migration flows. This creates a growing health problem in the EU that has not yet been effectively addressed by Member States (MS) authorities. The present study has been conducted with the aim of: (i) providing an overview of policies for MH in 10 EU member states (MS) (ii) analysing the challenges linked to these RD due to growing requirements imposed by population, mobility and migration trends and (iii) identifying gaps, proposing improvements on existing policies, or developing new ones to fit the identified needs.
de Aguirre-Neto JC, de Camargo B, van Tinteren H, Bergeron C, Brok J, Ramírez-Villar G, Verschuur A, Furtwängler R, Howell L, Saunders D, Olsen O, Coulomb A, Vokuhl C, Godzinski J, Smets AM, Vujanic GM, van den Heuvel-Eibrink MM, Graf N, Pritchard-Jones K	International Comparisons of Clinical Demographics and Outcomes in the International Society of Pediatric Oncology Wilms Tumor 2001 Trial and Study.	JCO global oncology 2022, 8:e2100425
International comparisons of patient demographics, tumor characteristics, and survival can shed light on areas for health care system improvement. The International Society of Pediatric Oncology Wilms Tumor 2001 trial/study registered patients through national clinical study groups in Western Europe and Brazil. This retrospective post hoc analysis of the International Society of Pediatric Oncology Wilms Tumor 2001 database aims to make visible and suggest reasons for any variations in outcomes.
Ahrens S, Hoffmann C, Jabar S, Braun-Munzinger G, Paulussen M, Dunst J, Rübe C, Winkelmann W, Heinecke A, Göbel U, Winkler K, Harms D, Treuner J, Jürgens H	Evaluation of prognostic factors in a tumor volume-adapted treatment strategy for localized Ewing sarcoma of bone.	Med Pediatr Oncol 1999, 32: 186
Aich A, Jones MK, Gupta K	Pain and sickle cell disease.	Current opinion in hematology 2019, 26: 131
Pain is a major comorbidity of sickle cell disease (SCD). Opioids are the mainstay for pain treatment but remain suboptimal. We discuss mechanism-based treatable targets devoid of opioids to prevent and/or treat SCD pain.
Ait-Tahar K, Damm-Welk C, Burkhardt B, Zimmermann M, Klapper W, Reiter A, Pulford K, Woessmann W	Correlation of the autoantibody response to the ALK oncoantigen in pediatric anaplastic lymphoma kinase-positive anaplastic large cell lymphoma with tumor dissemination and relapse risk.	Blood 2010, 115: 3314
Anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) constitutes an ideal model disease to study tumor-specific immune responses. All the tumor cells express oncogenic ALK resulting from a chromosomal translocation involved in lymphomagenesis. Although antibodies and T-cell responses to ALK have previously been detected in ALK-positive ALCL patients, their prognostic significance is unknown. We investigated a large cohort of uniformly treated ALK-positive pediatric ALCL patients to ascertain whether the titers of preexisting ALK autoantibodies correlated with clinical and histologic characteristics, tumor dissemination, and patient outcome. ALK autoantibodies were analyzed in pretherapeutic serum samples from 95 patients enrolled into 2 therapy studies between 1996 and 2007. ALK autoantibodies were detected in 87/95 patients. The titers inversely correlated with stage and amount of circulating tumor cells. High antibody titers correlated with significantly lower cumulative incidence of relapses (CI-R): titers > or = 1/60 750, n = 29, CI-R 11% +/- 6%; titers 1/2025-< 1/60 750, n = 39, CI-R 31% +/- 8%; and titers 0-< or = 1/750, n = 27, CI-R of 63% +/- 10% (P < .001). Our results provide the first clinical evidence that a robust preexisting immune response to an oncoantigen resulting from an oncogenic chromosomal translocation inhibits lymphoma dissemination and decreases the risk of relapse.
Aladjidi N, Leverger G, Leblanc T, Picat MQ, Michel G, Bertrand Y, Bader-Meunier B, Robert A, Nelken B, Gandemer V, Savel H, Stephan JL, Fouyssac F, Jeanpetit J, Thomas C, Rohrlich P, Baruchel A, Fischer A, Chêne G, Perel Y, Centre de Référence National des Cytopénies Auto-immunes de l'Enfant (CEREVANCE)	New insights into childhood autoimmune hemolytic anemia: a French national observational study of 265 children.	Haematologica 2011, 96: 655
Autoimmune hemolytic anemia is a rare condition in children. Little is known about its initial presentation and the subsequent progression of the disease.
Albright AL, Packer RJ, Zimmerman R, Rorke LB, Boyett J, Hammond GD	Magnetic resonance scans should replace biopsies for the diagnosis of diffuse brain stem gliomas: a report from the Children's Cancer Group.	Neurosurgery 1993, 33: 1026
Albrecht S, von Schweinitz D, Waha A, Kraus J, von Deimling A, Pietsch T	Loss of maternal alleles on chromosome arm 11p in hepatoblastoma.	Cancer Res 1994, 54: 5041
Albrecht S, Hartmann W, Houshdaran F, Koch A, Gartner B, Prawitt D, Zabel BU, Russo P, Von Schweinitz D, Pietsch T	Allelic loss but absence of mutations in the polyspecific transporter gene BWR1A on 11p15. 5 in hepatoblastoma.	International journal of cancer. Journal international du cancer 2004, 111: 627
Chromosomal region 11p15.5 shows frequent maternal allelic loss in embryonal tumors, including rhabdomyosarcoma (RMS), Wilms' tumor (WT) and hepatoblastoma (HB), consistent with the presence of at least one tumor suppressor gene in this region, which should be paternally imprinted, i.e., expressed from the maternal allele only. The BWR1A gene encodes a polyspecific transmembrane transporter and is located on 11p15.5. It is highly expressed in liver, paternally imprinted and was found to be mutated in an RMS cell line, making it a plausible tumor suppressor gene for HB. We therefore screened 62 HBs, 3 HB cell lines and 1 pediatric hepatocellular carcinoma for BWR1A mutations using single-strand conformation polymorphism analysis. Allelic loss on 11p15.5 was assessed by PCR-based microsatellite analysis in 56 of the cases for which constitutional DNA was available. BWR1A mRNA expression was determined in 14 HBs by differential RT-PCR of matched cDNA samples from tumor and normal liver. Western blot analysis was performed on 4 tumors and matching normal liver tissue. Except for sequence polymorphisms (in exons 2, 3 and 10 as well as in introns 6 and 7), no mutations were found. Thirteen HBs (23%) had allelic loss on 11p15.5; this included BWR1A in 12 but it was telomeric to BWR1A in 1. Expression of BWR1A mRNA was reduced in 11 out of 14 cases by 19-92%, independent from allelic loss of 11p15.5. By Western blot analysis, all 4 tumors and matching liver samples displayed a 48-51 kd band corresponding to BWR1A. These results make it unlikely that BWR1A is the target of the allelic deletions in HB. However, similar to the putative 11p15.5 tumor suppressor H19, BWR1A appears to be reduced in expression. Reduced expression in the absence of mutations may contribute to HB development; however, to understand the significance of this finding will require further studies on the function of BWR1A, specifically its role in liver development.
Albert MH, Bittner TC, Nonoyama S, Notarangelo LD, Burns S, Imai K, Espanol T, Fasth A, Pellier I, Strauss G, Morio T, Gathmann B, Noordzij JG, Fillat C, Hoenig M, Nathrath M, Meindl A, Pagel P, Wintergerst U, Fischer A, Thrasher AJ, Belohradsky BH, Ochs HD	X-linked thrombocytopenia (XLT) due to WAS mutations: clinical characteristics, long-term outcome, and treatment options.	Blood 2010, 115: 3231
A large proportion of patients with mutations in the Wiskott-Aldrich syndrome (WAS) protein gene exhibit the milder phenotype termed X-linked thrombocytopenia (XLT). Whereas stem cell transplantation at an early age is the treatment of choice for patients with WAS, therapeutic options for patients with XLT are controversial. In a retrospective multicenter study we defined the clinical phenotype of XLT and determined the probability of severe disease-related complications in patients older than 2 years with documented WAS gene mutations and mild-to-moderate eczema or mild, infrequent infections. Enrolled were 173 patients (median age, 11.5 years) from 12 countries spanning 2830 patient-years. Serious bleeding episodes occurred in 13.9%, life-threatening infections in 6.9%, autoimmunity in 12.1%, and malignancy in 5.2% of patients. Overall and event-free survival probabilities were not significantly influenced by the type of mutation or intravenous immunoglobulin or antibiotic prophylaxis. Splenectomy resulted in increased risk of severe infections. This analysis of the clinical outcome and molecular basis of patients with XLT shows excellent long-term survival but also a high probability of severe disease-related complications. These observations will allow better decision making when considering treatment options for individual patients with XLT.
Albert MH, Notarangelo LD, Ochs HD	Clinical spectrum, pathophysiology and treatment of the Wiskott-Aldrich syndrome.	Current opinion in hematology 2011, 18: 42
The Wiskott-Aldrich syndrome (WAS), caused by mutations in the WAS gene, is a complex and diverse disorder with X-linked inheritance. This review focuses on recent developments in the understanding of its basic pathophysiology, diverse clinical phenotypes and optimal patient management including novel therapies.
Albert MH, Freeman AF	Wiskott-Aldrich Syndrome (WAS) and Dedicator of Cytokinesis 8- (DOCK8) Deficiency.	Frontiers in pediatrics 2019, 7: 451
Both Wiskott-Aldrich syndrome (WAS) and dedicator of cytokinesis 8 (DOCK8) deficiency are primary immunodeficiency diseases caused by mutations in genes that result in defective organization of the cytoskeleton in hematopoietic tissues. They share some overlapping features such as a combined immunodeficiency, eczema and a predisposition to autoimmunity and malignancy, but also have some unique features that make them relatively easy to diagnose by clinical means. Both diseases can be cured by HSCT in a large proportion of patients. In WAS it is sometimes difficult to establish an indication for HSCT due to the large variability of disease severity, while HSCT is probably indicated in all patients affected by DOCK8 deficiency. There is considerably more published HSCT experience for WAS than for DOCK8 deficiency, but many open questions remain, which will be discussed in this review.
Albert MH, Slatter MA, Gennery AR, Güngör T, Bakunina K, Markovitch B, Hazelaar S, Sirait T, Courteille V, Aiuti A, Aleinikova OV, Balashov D, Bernardo ME, Bodova I, Bruno B, Cavazzana M, Chiesa R, Fischer A, Hauck F, Ifversen M, Kałwak K, Klein C, Kulagin A, Kupesiz A, Kuskonmaz B, Lindemans CA, Locatelli F, Lum SH, Maschan A, Meisel R, Moshous D, Porta F, Sauer MG, Sedlacek P, Schulz A, Suarez F, Vallée TC, Winiarski JH, Zecca M, Neven B, Veys P, Lankester AC	Hematopoietic stem cell transplantation for Wiskott-Aldrich syndrome: an EBMT Inborn Errors Working Party analysis.	Blood 2022, 139: 2066
Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for patients affected by Wiskott-Aldrich syndrome (WAS). Reported HSCT outcomes have improved over time with respect to overall survival, but some studies have identified older age and HSCT from alternative donors as risk factors predicting poorer outcome. We analyzed 197 patients undergoing transplant at European Society for Blood and Marrow Transplantation centers between 2006 and 2017 who received conditioning as recommended by the Inborn Errors Working Party (IEWP): either busulfan (n = 103) or treosulfan (n = 94) combined with fludarabine ± thiotepa. After a median follow-up post-HSCT of 44.9 months, 176 patients were alive, resulting in a 3-year overall survival of 88.7% and chronic graft-versus-host disease (GVHD)-free survival (events include death, graft failure, and severe chronic GVHD) of 81.7%. Overall survival and chronic GVHD-free survival were not significantly affected by conditioning regimen (busulfan- vs treosulfan-based), donor type (matched sibling donor/matched family donor vs matched unrelated donor/mismatched unrelated donor vs mismatched family donor), or period of HSCT (2006-2013 vs 2014-2017). Patients aged <5 years at HSCT had a significantly better overall survival. The overall cumulative incidences of grade III to IV acute GVHD and extensive/moderate/severe chronic GVHD were 6.6% and 2.1%, respectively. Patients receiving treosulfan-based conditioning had a higher incidence of graft failure and mixed donor chimerism and more frequently underwent secondary procedures (second HSCT, unconditioned stem cell boost, donor lymphocyte infusion, or splenectomy). In summary, HSCT for WAS with conditioning regimens currently recommended by IEWP results in excellent survival and low rates of GVHD, regardless of donor or stem cell source, but age ≥5 years remains a risk factor for overall survival.
Allen JC, Helson L	High-dose cyclophosphamide chemotherapy for recurrent CNS tumors in children.	Journal of neurosurgery 1981, 55: 749
A Phase Ii chemotherapy trial was conducted in 18 children with recurrent brain tumors, using high doses (80 mg/kg or greater) of intravenous cyclophosphamide cyclophosphamide. All eight patients with medulloblastomas responded; two patients with systemic metastases had complete responses and six others had partial responses. In seven patients with gliomas, there were one complete and four partial responses. In a third group, all three patients with intracranial germ-cell tumors had partial responses. The overall response rate was, therefore, 89% (16 of 18 patients), and the mean duration of response was 7 months (range 2 to 24 or more months). The hematological toxicity was considerable, with two deaths possibly related to chemotherapy: one patient, a recipient of unirradiated packed cells, died from a graft versus host reaction, and the other died from an intracranial hemorrhage during a thrombocytopenic episode. Four patients had prior chemotherapy, and 10 patients had prior neuraxis radiation therapy. These patients tolerated aggressive chemotherapy reasonably well. The results are sufficiently encouraging to justify a Phase III trial in patients with newly diagnosed disease.
Allen JC, Donahue B, DaRosso R, Nirenberg A	Hyperfractionated craniospinal radiotherapy and adjuvant chemotherapy for children with newly diagnosed medulloblastoma and other primitive neuroectodermal tumors.	International journal of radiation oncology, biology, physics 1996, 36: 1155
PURPOSE: This single-institution Phase III study conducted from 1989 to 1995 evaluates the feasibility of a multimodality protocol combining hyperfractionated craniospinal radiotherapy (HFRT) followed by adjuvant chemotherapy in 23 patients with newly diagnosed primitive neuroectodermal tumors (PNET) arising in the central nervous system. METHODS AND MATERIALS: All 23 patients had a histologically confirmed PNET and were over 3 years of age at diagnosis. The eligibility criteria for PNET patients with cerebellar primaries (medulloblastoma) included either a high T stage (T3b or 4) or high M stage (M1-3). All patients with noncerebellar primaries were eligible regardless of T or M stage. The median age of the 23 patients was 9 years (mean 3-25); 11 were female. The primary tumor arose in the cerebellum in 19. Of these medulloblastoma patients, 15 had high T stages (T3b or T4) with large locally invasive tumors and no evidence of metastases (M0), constituting Group 1. Thirteen (86%) of these patients had gross total resections. Four other medulloblastoma patients had both high T and high M stages, constituting Group 2. Group 3 consisted of four other patients with exocerebellar primaries (two brain, one brain stem, and one cauda equina), three of whom were M3. Hyperfractionated radiotherapy was administered within 4 weeks of surgery. Twice-daily 1-Gy fractions were administered separated by 4-6 h. The total dose to the primary intracranial tumor and other areas of measurable intracranial disease was 72 Gy. The prophylactic craniospinal axis dose was 36 Gy, and boosts of 44-56 Gy were administered to metastatic spinal deposits. Following radiotherapy, monthly courses of multiagent chemotherapy were administered sequentially (cyclophosphamide-vincristine followed by cisplatin-etoposide followed by carboplatin-vincristine) for a total of 9 months. RESULTS: All patients completed radiotherapy as planned. Only three patients lost >10% of their body weight. One patient had clinically apparent radiation-induced esophagitis. The mean white blood count (WBC) nadir was 2.5/dl, and hematologic recovery occurred in all within 4 weeks of completing HFRT without the need of granulocyte-colony-stimulating factor. Two patients refused adjuvant chemotherapy, 3 patients experienced tumor progression during chemotherapy, and 2 of 18 remaining patients could not tolerate the full 9 months owing to hematologic toxicity. Of the 15 patients (93%) in Group 1, 14 remain in continuous remission for a median of 78 months, and none have died. Two of four patients in Group 2 are in continuous remission at 67 and 35 months, and two died at 18 and 30 months. One of the two patients in Group 2 who died refused adjuvant chemotherapy and developed tumor progression in the bone marrow. None of the three patients in Group 3 with evaluable disease (M3) had a complete response to therapy, and eventually all four died of progressive or recurrent disease. CONCLUSION: This multimodality protocol is feasible in the short term, and long-term monitoring of neurocognitive and neuroendocrine effects are in progress. Excellent long-term disease control has been achieved for medulloblastoma patients with high T stages who were M0 at diagnosis (Group 1), the majority of whom had gross total resections. This group has a progression-free survival of 95% after a median period of follow-up of 6.5 years. Alternative treatment strategies must be developed for patients with high M stages, as five of seven patients died of progressive or recurrent disease.
Allen KJ, Gurrin LC, Constantine CC, Osborne NJ, Delatycki MB, Nicoll AJ, McLaren CE, Bahlo M, Nisselle AE, Vulpe CD, Anderson GJ, Southey MC, Giles GG, English DR, Hopper JL, Olynyk JK, Powell LW, Gertig DM	Iron-overload-related disease in HFE hereditary hemochromatosis.	The New England journal of medicine 2008, 358: 221
Most persons who are homozygous for C282Y, the HFE allele most commonly asssociated with hereditary hemochromatosis, have elevated levels of serum ferritin and transferrin saturation. Diseases related to iron overload develop in some C282Y homozygotes, but the extent of the risk is controversial.
Allard P, Alhaj N, Lobitz S, Cario H, Jarisch A, Grosse R, Oevermann L, Hakimeh D, Tagliaferri L, Kohne E, Kopp-Schneider A, Kulozik AE, Kunz JB	Genetic modifiers of fetal hemoglobin affect the course of sickle cell disease in patients treated with hydroxyurea.	Haematologica 2022, 107: 1577
The course of sickle cell disease (SCD) is modified by polymorphisms boosting fetal hemoglobin (HbF) synthesis. However, it has remained an open question how these polymorphisms affect patients who are treated with the HbF-inducing drug hydroxyurea/ hydroxycarbamide. The German SCD registry offers the opportunity to answer this question, because >90% of patients are treated according to national guidelines recommending the use of hydroxyurea in all patients above 2 years of age. We analyzed the modifying effect of HbF-related genetic polymorphisms in 417 patients with homozygous SCD >2 years old who received hydroxyurea. HbF levels were correlated with higher total hemoglobin levels, lower rates of hemolysis, a lower frequency of painful crises and of red blood cell transfusions. The minor alleles of the polymorphisms in the γ-globin promoter (rs7482144), BCL11A (rs1427407) and HMIP (rs66650371) were strongly associated with increased HbF levels. However, these associations did not translate into lower frequencies of vaso-occlusive events which did not differ between patients either carrying or not carrying the HMIP and BCL11A polymorphisms. Patients on hydroxyurea carrying the γ-globin promoter polymorphism demonstrated substantially higher hemoglobin levels (P<10-4) but also higher frequencies of painful crises and hospitalizations (P<0.01) when compared to patients without this polymorphism. Taken together, these data indicate that the γ-globin, HMIP and BCL11A polymorphisms correlate with increased HbF in SCD patients on hydroxyurea. While HbF is negatively correlated with the frequency of painful crises and hospitalizations, this was not observed for the presence of known HbF-boosting alleles.
Alter BP	Cancer in Fanconi anemia, 1927-2001.	Cancer 2003, 97: 425
Fanconi anemia (FA) is an autosomal recessive disease associated with an abnormal response to DNA damage. Although FA is well known for the association of aplastic anemia and characteristic birth defects, leukemia and solid tumors also occur at a high rate in this group of patients. A review of all reported cases is informative with regard to the specific types of cancer, the ages at which they occur, and the cumulative probability of their development.
Althaus K, Najm J, Greinacher A	MYH9 Related Platelet Disorders - Often Unknown and Misdiagnosed.	Klinische Padiatrie 2011, 223, 120
MYH9 related platelet disorders are a relatively rare cause of thrombocytopenia. Located on chromosome 22, the MYH9 gene encodes the motorprotein non-muscular myosin heavy chain IIA (NMMHCIIA). Heterozygous defects in this gene lead to 4 different autosomal dominant syndromes namely May-Hegglin anomaly, Epstein syndrome, Fechtner syndrome and Sebastian platelet syndrome. All 4 syndromes are characterized by macrothrombocytopenia and a mild bleeding tendency. Depending on the position of the causative mutation within the gene, the risk increases for syndromic manifestations such as renal failure, hearing loss and pre-senile cataract. Mutations in the neck region of the NMMHCIIA protein are more likely associated with these comorbidities than mutations in the N- or C-terminal part of the gene. MYH9 related platelet disorders should be excluded in patients with chronic thrombocytopenia and large platelets. Most sensitive for diagnosis/exclusion are immunofluorescence studies using a blood smear. The biggest risk for these patients is ineffective but potentially harmful treatment based on the misdiagnosis of immune thrombocytopenia. This review provides a workflow for diagnosis and treatment of MYH9 related thrombocytopenia.
Alter BP	Fanconi anemia and the development of leukemia.	Best practice & research. Clinical haematology 2014, 27(3-4): 214
Fanconi anemia (FA) is a rare autosomal recessive cancer-prone inherited bone marrow failure syndrome, due to mutations in 16 genes, whose protein products collaborate in a DNA repair pathway. The major complications are aplastic anemia, acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and specific solid tumors. A severe subset, due to mutations in FANCD1/BRCA2, has a cumulative incidence of cancer of 97% by age 7 years; the cancers are AML, brain tumors, and Wilms tumor; several patients have multiple events. Patients with the other genotypes (FANCA through FANCQ) have cumulative risks of more than 50% of marrow failure, 20% of AML, and 30% of solid tumors (usually head and neck or gynecologic squamous cell carcinoma), by age 40, and they too are at risk of multiple adverse events. Hematopoietic stem cell transplant may cure AML and MDS, and preemptive transplant may be appropriate, but its use is a complicated decision.
Alten J, Klapper W, Leuschner I, Eckert C, Beier R, Vallo E, Krause M, Claviez A, Vieth S, Bleckmann K, Möricke A, Schrappe M, Cario G	Secondary histiocytic sarcoma may cause apparent persistence or recurrence of minimal residual disease in childhood acute lymphoblastic leukemia.	Pediatr Blood Cancer 2015, 62: 1656
Histiocytic sarcoma (HS) is a rare disease with poor prognosis which may develop subsequent to acute lymphoblastic leukemia (ALL). Here we report two children treated within the AIEOP-BFM ALL 2009 trial: one patient succumbed to fulminant hemophagocytic lymphohistiocytosis triggered by HS during ALL maintenance therapy, the other patient had a smoldering course of HS for over 2 years, and subsequently died after allogeneic stem cell transplantation. In both cases, HS and ALL were clonally related and apparent return of minimal residual disease (MRD) was detected by qPCR in bone marrow. Thus, HS should be considered in ALL when MRD appears to persist or reappear.
Altintas B, Giri N, McReynolds LJ, Best A, Alter BP	Genotype-phenotype and outcome associations in patients with Fanconi anemia: The National Cancer Institute cohort.	Haematologica 2022,
Fanconi anemia (FA) is caused by pathogenic variants in the FA/BRCA DNA repair pathway genes, and is characterized by congenital abnormalities, bone marrow failure (BMF) and increased cancer risk. We conducted a genotype-phenotype and outcomes study of 203 patients with FA in our cohort. We compared across the genes, FA/BRCA DNA repair pathways (upstream, ID complex and downstream), and type of pathogenic variants (hypomorphic or null). We explored differences between the patients evaluated in our clinic (clinic cohort) and those who provided data remotely (field cohort). Patients with variants in upstream complex pathway had less severe phenotype [lacked VACTERL-H (Vertebral, Anal, Cardiac, Trachea-esophageal fistula, Esophageal/duodenal atresia, Renal, Limb, Hydrocephalus) association and/or PHENOS (Pigmentation, small-Head, small-Eyes, Neurologic, Otologic, Short stature) features]. ID complex was associated with VACTERL-H. The clinic cohort had more PHENOS features than the field cohort. PHENOS was associated with increased risk of BMF, and VACTERL-H with hypothyroidism. The cumulative incidence of severe BMF was 70%, solid tumors (ST) 20% and leukemia 6.5% as the first event. Head and neck and gynecological cancers were the most common ST, with further increased risk after hematopoietic cell transplantation. Among patients with FANCA, variants in exons 27-30 were associated with higher frequency of ST. Overall median survival was 37 years; patients with leukemia or FANCD1/BRCA2 variants had poorest survival. Patients with variants in the upstream complex had better survival than ID or downstream complex (p=0.001 and 0.016, respectively). FA is phenotypically and genotypically heterogeneous; detailed characterization provides new insights towards understanding this complex syndrome and guiding clinical management.
Alvarez O, Rodriguez MM, Jordan L, Sarnaik S	Renal medullary carcinoma and sickle cell trait: A systematic review.	Pediatric blood & cancer 2015, 62: 1694
Sickle cell trait (SCT) carries a small risk of renal medullary carcinoma (RMC). We conducted a systematic literature review and reported new four RMC cases (total N = 217). Eighty eight percent had SCT and 8% had sickle cell disease; 50% were children. Males had 2.4× risk than females. Isolated hematuria or in combination with abdominal or flank pain was the presenting sign in 66% cases. Tumor-related mortality was 95%. Four non-metastatic patients were long-term disease-free survivors. Although risk appears to be very low, individuals with SCT should be informed about the low risk of RMC with the hope of early diagnosis. Hematuria should prompt immediate investigation. Pediatr Blood Cancer 2015;62:1694-1699. © 2015 Wiley Periodicals, Inc.
Ambros I, Attarbaschi A, Rumpler S, Luegmayr A, Turkof E, Gadner H, Ambros P	Neuroblastoma cells provoke Schwann cell proliferation in vitro.	Med Pediatr Oncol 2001, 36: 163
Ambros P, Ambros I	Pathology and biology guidelines for resectable and unresectable neuroblastic tumors and bone marrow examination guidelines.	Med Pediatr Oncol 2001, 37: 492
Ambros P, Ambros I, Kerbl R, Luegmayr A, Rumpler S, Ladenstein R, Amann G, Kovar H, Horcher E, De Bernardi B, Michon J, Gadner H	Intratumoural heterogeneity of 1p deletions and MYCN amplification in neuroblastomas.	Med Pediatr Oncol 2001, 36: 1
American Psychiatric Association	Statistical Manual for Mental Disorders.	2002 4th edition,
Amouri M, Mesrati H, Chaaben H, Masmoudi A, Mseddi M, Turki H	Congenital hemangioma.	Cutis 2017, 99:E31-E33
Andrassy RJ, Chwals WJ	Nutritional support of the pediatric oncology patient.	Nutrition 1998, 14: 124
Anderer G, Schrappe M, Brechlin A, Lauten M, Muti P, Welte K, Stanulla M	Polymorphisms within glutathione S-transferase genes and initial response to glucocorticoids in childhood acute lymphoblastic leukaemia.	Pharmacogenetics 2000, 10: 715
Anderson FS, Kunin-Batson AS	Neurocognitive late effects of chemotherapy in children: the past 10 years of research on brain structure and function.	Pediatric blood & cancer 2009, 52: 159
Andreiuolo F, Le Teuff G, Bayar MA, Kilday JP, Pietsch T, von Bueren AO, Witt H, Korshunov A, Modena P, Pfister SM, Pagès M, Castel D, Giangaspero F, Chimelli L, Varlet P, Rutkowski S, Frappaz D, Massimino M, Grundy R, Grill J, SIOP Ependymoma Biology Working Group BIOMECA (BIOlogical Markers for Ependymomas in Children and Adolescents)	Integrating Tenascin-C protein expression and 1q25 copy number status in pediatric intracranial ependymoma prognostication: A new model for risk stratification.	PloS one 2017, 12:e0178351
Despite multimodal therapy, prognosis of pediatric intracranial ependymomas remains poor with a 5-year survival rate below 70% and frequent late deaths.
Andres O, Henning K, Strauß G, Pflug A, Manukjan G, Schulze H	Diagnosis of platelet function disorders: A standardized, rational, and modular flow cytometric approach.	Platelets 2018, 29: 347
Andreou D, Ranft A, Gosheger G, Timmermann B, Ladenstein R, Hartmann W, Bauer S, Baumhoer D, van den Berg H, Dijkstra PDS, Dürr HR, Gelderblom H, Hardes J, Hjorth L, Kreyer J, Kruseova J, Leithner A, Scobioala S, Streitbürger A, Tunn PU, Wardelmann E, Windhager R, Jürgens H, Dirksen U, GPOH-Euro-EWING99 consortium	Which Factors Are Associated with Local Control and Survival of Patients with Localized Pelvic Ewing's Sarcoma? A Retrospective Analysis of Data from the Euro-EWING99 Trial.	Clinical orthopaedics and related research 2020, 478: 290
Local treatment of pelvic Ewing's sarcoma may be challenging, and intergroup studies have focused on improving systemic treatments rather than prospectively evaluating aspects of local tumor control. The Euro-EWING99 trial provided a substantial number of patients with localized pelvic tumors treated with the same chemotherapy protocol. Because local control included surgical resection, radiation therapy, or a combination of both, we wanted to investigate local control and survival with respect to the local modality in this study cohort.
DeAngelis LM, Tong WP, Lin S, Fleisher M, Bertino JR	Carboxypeptidase G2 rescue after high-dose methotrexate.	J Clin Oncol 1996, 14: 2145
This study was a pilot project to assess the safety and efficacy of carboxypeptidase G2 (CPG2) rescue from high-dose (HD) methotrexate (MTX) in patients with recurrent cerebral lymphoma.
Angastiniotis M, Lobitz S	Thalassemias: An Overview.	International journal of neonatal screening 2019, 5: 16
Thalassemia syndromes are among the most serious and common genetic conditions. They are indigenous in a wide but specific geographical area. However, through migration they are spreading across regions not previously affected. Thalassemias are caused by mutations in the α () and β globin () genes and are usually inherited in an autosomal recessive manner. The corresponding proteins form the adult hemoglobin molecule (HbA) which is a heterotetramer of two α and two β globin chains. Thalassemia-causing mutations lead to an imbalanced globin chain production and consecutively to impaired erythropoiesis. The severity of the disease is largely determined by the degree of chain imbalance. In the worst case, survival is dependent on regular blood transfusions, which in turn cause transfusional iron overload and secondary multi-organ damage due to iron toxicity. A vigorous monitoring and treatment regime is required, even for the milder syndromes. Thalassemias are a major public health issue in many populations which many health authorities fail to address. Even though comprehensive care has resulted in long-term survival and good quality of life, poor access to essential components of management results in complications which increase the cost of treatment and lead to poor outcomes. These requirements are not recognized by measures such as the Global Burden of Disease project, which ranks thalassemia very low in terms of disability-adjusted life years (DALYs), and fails to consider that it ranks highly in the one to four-year-old age group, making it an important contributor to under-5 mortality. Thalassemia does not fulfil the criteria to be accepted as a target disease for neonatal screening. Nevertheless, depending on the screening methodology, severe cases of thalassemia will be detected in most neonatal screening programs for sickle cell disease. This is very valuable because: (1) it helps to prepare the affected families for having a sick child and (2) it is an important measure of secondary prevention.
Anteby I, Ramu N, Gradstein L, Miskin H, Pe'er J, Benezra D	Ocular and orbital complications following the treatment of retinoblastoma.	European journal of ophthalmology 1998, 8: 106
PURPOSE: To investigate the ocular and orbital complications observed in children treated for retinoblastoma. SUBJECTS AND METHODS. We retrospectively studied 73 children (39 boys, 34 girls) suffering from retinoblastoma. Thirty-six had bilateral tumor and 37 unilateral disease for a total of 109 eyes affected. The follow-up was 6-180 months (median 36 months). Enucleation was the most common initial treatment approach in the unilateral group, and radiotherapy (by external beam) was the most common initial therapy in the bilateral group. Cryotherapy, photocoagulation, brachytherapy and/or systemic chemotherapy were used as adjuvant treatments when necessary. Ocular complications were recorded at the follow-up examinations. RESULTS. Cataract developed in 20% of the irradiated eyes. The mean time from irradiation until development of cataract was 28.5 months (6-64 months). Radiation retinopathy developed in 12% and was first detected 11-72 months (mean 37 months) after irradiation therapy. Mild transient keratopathy was observed in all eyes undergoing irradiation, and xerophthalmia in one eye. Complications after enucleation included: marked discharge from the socket (11.0%), extrusion of the implant (9.6%), and contraction of the socket (3.0%). No complications were observed after cryotherapy or laser photocoagulation of the tumor. CONCLUSIONS. Ocular complications after treating children with retinoblastoma are common and may seriously affect the quality of life of children surviving the primary malignancy.
Antunes AT, Goos YJ, Pereboom TC, Hermkens D, Wlodarski MW, Da Costa L, MacInnes AW	Ribosomal Protein Mutations Result in Constitutive p53 Protein Degradation through Impairment of the AKT Pathway.	PLoS genetics 2015, 11:e1005326
Mutations in ribosomal protein (RP) genes can result in the loss of erythrocyte progenitor cells and cause severe anemia. This is seen in patients with Diamond-Blackfan anemia (DBA), a pure red cell aplasia and bone marrow failure syndrome that is almost exclusively linked to RP gene haploinsufficiency. While the mechanisms underlying the cytopenia phenotype of patients with these mutations are not completely understood, it is believed that stabilization of the p53 tumor suppressor protein may induce apoptosis in the progenitor cells. In stark contrast, tumor cells from zebrafish with RP gene haploinsufficiency are unable to stabilize p53 even when exposed to acute DNA damage despite transcribing wild type p53 normally. In this work we demonstrate that p53 has a limited role in eliciting the anemia phenotype of zebrafish models of DBA. In fact, we find that RP-deficient embryos exhibit the same normal p53 transcription, absence of p53 protein, and impaired p53 response to DNA damage as RP haploinsufficient tumor cells. Recently we reported that RP mutations suppress activity of the AKT pathway, and we show here that this suppression results in proteasomal degradation of p53. By re-activating the AKT pathway or by inhibiting GSK-3, a downstream modifier that normally represses AKT signaling, we are able to restore the stabilization of p53. Our work indicates that the anemia phenotype of zebrafish models of DBA is dependent on factors other than p53, and may hold clinical significance for both DBA and the increasing number of cancers revealing spontaneous mutations in RP genes.
Apps JR, Muller HL, Hankinson TC, Yock TI, Martinez-Barbera JP	Contemporary Biological Insights and Clinical Management of Craniopharyngioma.	Endocrine reviews 2023, 44: 518
Craniopharyngiomas (CPs) are clinically aggressive tumors because of their invasive behavior and recalcitrant tendency to recur after therapy. There are 2 types based on their distinct histology and molecular features: the papillary craniopharyngioma (PCP), which is associated with BRAF-V600E mutations and the adamantinomatous craniopharyngioma (ACP), characterized by mutations in CTNNB1 (encoding β-catenin). Patients with craniopharyngioma show symptoms linked to the location of the tumor close to the optic pathways, hypothalamus, and pituitary gland, such as increased intracranial pressure, endocrine deficiencies, and visual defects. Treatment is not specific and mostly noncurative, and frequently includes surgery, which may achieve gross total or partial resection, followed by radiotherapy. In cystic tumors, frequent drainage is often required and intracystic instillation of drugs has been used to help manage cyst refilling. More recently targeted therapies have been used, particularly in PCP, but also now in ACP and clinical trials are underway or in development. Although patient survival is high, the consequences of the tumor and its treatment can lead to severe comorbidities resulting in poor quality of life, in particular for those patients who bear tumors with hypothalamic involvement. Accordingly, in these patients at risk for the development of a hypothalamic syndrome, hypothalamus-sparing treatment strategies such as limited resection followed by irradiation are recommended. In this review, we provide an update on various aspects of CP, with emphasis on recent advances in the understanding of tumor pathogenesis, clinical consequences, management, and therapies.
Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW	The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia.	Blood 2016 May 19; 127: 2391
The World Health Organization (WHO) classification of tumors of the hematopoietic and lymphoid tissues was last updated in 2008. Since then, there have been numerous advances in the identification of unique biomarkers associated with some myeloid neoplasms and acute leukemias, largely derived from gene expression analysis and next-generation sequencing that can significantly improve the diagnostic criteria as well as the prognostic relevance of entities currently included in the WHO classification and that also suggest new entities that should be added. Therefore, there is a clear need for a revision to the current classification. The revisions to the categories of myeloid neoplasms and acute leukemia will be published in a monograph in 2016 and reflect a consensus of opinion of hematopathologists, hematologists, oncologists, and geneticists. The 2016 edition represents a revision of the prior classification rather than an entirely new classification and attempts to incorporate new clinical, prognostic, morphologic, immunophenotypic, and genetic data that have emerged since the last edition. The major changes in the classification and their rationale are presented here.
Ardon H, De Vleeschouwer S, Van Calenbergh F, Claes L, Kramm CM, Rutkowski S, Wolff JE, Van Gool SW	Adjuvant dendritic cell-based tumour vaccination for children with malignant brain tumours.	Pediatric blood & cancer 2010, 54: 519
BACKGROUND: A large experience with dendritic cell (DC)-based vaccination for malignant brain tumours has been gained in adults. Here we focus on the results obtained in children with relapsed malignant brain tumours. PROCEDURE: In total 45 children were vaccinated: 33 high grade glioma (HGG), 5 medulloblastoma (MB)/primitive neuro-ectodermal tumour (PNET), 4 ependymoma and 3 atypical teratoid-rhabdoid tumour (ATRT). Autologous, monocyte-derived DC were generated and loaded with tumour lysate, which was used as source of tumour-associated antigens. RESULTS: In 38 patients peripheral blood mononuclear cells (PBMC) were obtained from leukapheresis and in 7 patients from fresh blood samples. 7 HGG patients are still alive with median follow-up (FU) of 35.7 months (range: 12.1-85.6). Median overall survival (OS) was 13.5 months (range: 1.4-85.6). All patients with MB/PNET died (median OS 5.7 months; range 4.3-51.2). One patient with ependymoma is still alive at 22.3 months FU. The other three patients died at, respectively, 7.7, 30.1 and 31.5 months. Two patients with ATRT are still alive at, respectively, 34.1 and 52.6 months FU. The third patient died at 50.5 months. No severe adverse events were noticed. CONCLUSIONS: In this exploratory study, HGG and ATRT seem to respond more favourably to vaccination than MB/PNET and ependymoma. Although preliminary, our results are promising and support further testing of DC-based immunotherapy in new treatment protocols for HGG and ATRT.
Arico M, Valsecchi M, Camitta B, Schrappe M, Chessells J, Baruchel A, Gaynon P, Silverman L, Janka-Schaub G, Kamps W, Pui C, Masera G	Outcome of treatment in children with Philadelphia chromosome-positive acute lymphoblastic leukemia.	N Engl J Med 2000, 342: 998
Arlt B, Zasada C, Baum K, Wuenschel J, Mastrobuoni G, Lodrini M, Astrahantseff K, Winkler A, Schulte JH, Finkler S, Forbes M, Hundsdoerfer P, Guergen D, Hoffmann J, Wolf J, Eggert A, Kempa S, Deubzer HE	Inhibiting phosphoglycerate dehydrogenase counteracts chemotherapeutic efficacy against MYCN-amplified neuroblastoma.	International journal of cancer 2021, 148: 1219
Here we sought metabolic alterations specifically associated with MYCN amplification as nodes to indirectly target the MYCN oncogene. Liquid chromatography-mass spectrometry-based proteomics identified seven proteins consistently correlated with MYCN in proteomes from 49 neuroblastoma biopsies and 13 cell lines. Among these was phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme in de novo serine synthesis. MYCN associated with two regions in the PHGDH promoter, supporting transcriptional PHGDH regulation by MYCN. Pulsed stable isotope-resolved metabolomics utilizing C-glucose labeling demonstrated higher de novo serine synthesis in MYCN-amplified cells compared to cells with diploid MYCN. An independence of MYCN-amplified cells from exogenous serine and glycine was demonstrated by serine and glycine starvation, which attenuated nucleotide pools and proliferation only in cells with diploid MYCN but did not diminish these endpoints in MYCN-amplified cells. Proliferation was attenuated in MYCN-amplified cells by CRISPR/Cas9-mediated PHGDH knockout or treatment with PHGDH small molecule inhibitors without affecting cell viability. PHGDH inhibitors administered as single-agent therapy to NOG mice harboring patient-derived MYCN-amplified neuroblastoma xenografts slowed tumor growth. However, combining a PHGDH inhibitor with the standard-of-care chemotherapy drug, cisplatin, revealed antagonism of chemotherapy efficacy in vivo. Emergence of chemotherapy resistance was confirmed in the genetic PHGDH knockout model in vitro. Altogether, PHGDH knockout or inhibition by small molecules consistently slows proliferation, but stops short of killing the cells, which then establish resistance to classical chemotherapy. Although PHGDH inhibition with small molecules has produced encouraging results in other preclinical cancer models, this approach has limited attractiveness for patients with neuroblastoma.
Armenian SH, Sun CL, Kawashima T, Arora M, Leisenring W, Sklar CA, Baker KS, Francisco L, Teh JB, Mills G, Wong FL, Rosenthal J, Diller LR, Hudson MM, Oeffinger KC, Forman SJ, Robison LL, Bhatia S	Long-term health-related outcomes in survivors of childhood cancer treated with HSCT versus conventional therapy: a report from the Bone Marrow Transplant Survivor Study (BMTSS) and Childhood Cancer Survivor Study (CCSS).	Blood 2011 Aug 4; 118: 1413
HSCT is being increasingly offered as a curative option for children with hematologic malignancies. Although survival has improved, the long-term morbidity ascribed to the HSCT procedure is not known. We compared the risk of chronic health conditions and adverse health among children with cancer treated with HSCT with survivors treated conventionally, as well as with sibling controls. HSCT survivors were drawn from BMTSS (N = 145), whereas conventionally treated survivors (N = 7207) and siblings (N = 4020) were drawn from CCSS. Self-reported chronic conditions were graded with CTCAEv3.0. Fifty-nine percent of HSCT survivors reported ≥ 2 conditions, and 25.5% reported severe/life-threatening conditions. HSCT survivors were more likely than sibling controls to have severe/life-threatening (relative risk [RR] = 8.1, P < .01) and 2 or more (RR = 5.7, P < .01) conditions, as well as functional impairment (RR = 7.7, P < .01) and activity limitation (RR = 6.3, P < .01). More importantly, compared with CCSS survivors, BMTSS survivors demonstrated significantly elevated risks (severe/life-threatening conditions: RR = 3.9, P < .01; multiple conditions: RR = 2.6, P < .01; functional impairment: RR = 3.5, P < .01; activity limitation: RR = 5.8, P < .01). Unrelated donor HSCT recipients were at greatest risk. Childhood HSCT survivors carry a significantly greater burden of morbidity not only compared with noncancer populations but also compared with conventionally treated cancer patients, providing evidence for close monitoring of this high-risk population.
Arnhold V, Schmelz K, Proba J, Winkler A, Wünschel J, Toedling J, Deubzer HE, Künkele A, Eggert A, Schulte JH, Hundsdoerfer P	Reactivating TP53 signaling by the novel MDM2 inhibitor DS-3032b as a therapeutic option for high-risk neuroblastoma.	Oncotarget 2018 Jan 5; 9: 2304
Fewer than 50% of patients with high-risk neuroblastoma survive five years after diagnosis with current treatment protocols. Molecular targeted therapies are expected to improve survival. Although MDM2 has been validated as a promising target in preclinical models, no MDM2 inhibitors have yet entered clinical trials for neuroblastoma patients. Toxic side effects, poor bioavailability and low efficacy of the available MDM2 inhibitors that have entered phase I/II trials drive the development of novel MDM2 inhibitors with an improved risk-benefit profile. We investigated the effect of the novel MDM2 small molecular inhibitor, DS-3032b, on viability, proliferation, senescence, migration, cell cycle arrest and apoptosis in a panel of six neuroblastoma cell lines with different and genetic backgrounds, and assessed efficacy in a murine subcutaneous model for high-risk neuroblastoma. Re-analysis of existing expression data from 476 primary neuroblastomas showed that high-level expression correlated with poor patient survival. DS-3032b treatment enhanced TP53 target gene expression and induced G1 cell cycle arrest, senescence and apoptosis. CRISPR-mediated knockout in neuroblastoma cells mimicked DS-3032b treatment. TP53 signaling was selectively activated by DS-3032b in neuroblastoma cells with wildtype , regardless of the presence of amplification, but was significantly reduced by mutations or expression of a dominant-negative TP53 mutant. Oral DS-3032b administration inhibited xenograft tumor growth and prolonged mouse survival. Our and data demonstrate that DS-3032b reactivates TP53 signaling even in the presence of amplification in neuroblastoma cells, to reduce proliferative capacity and cause cytotoxicity.
Arzneimittelkommission der deutschen Ärzteschaft	Neue Arzneimittel.	2018 online publiziert aufgerufen am 1.12.2021
Asberg A, Hveem K, Thorstensen K, Ellekjter E, Kannelønning K, Fjøsne U, Halvorsen TB, Smethurst HB, Sagen E, Bjerve KS	Screening for hemochromatosis: high prevalence and low morbidity in an unselected population of 65,238 persons.	Scandinavian journal of gastroenterology 2001, 36: 1108
Hereditary hemochromatosis (HH) is a common genetic disease leading to accumulation of iron in several organs, most notably the liver. The C282Y/C282Y mutation in the HFE gene is found in most cases. In order to prevent clinical disease and to study the cost and feasibility of screening, a large population was screened.
Aschemeyer S, Qiao B, Stefanova D, Valore EV, Sek AC, Ruwe TA, Vieth KR, Jung G, Casu C, Rivella S, Jormakka M, Mackenzie B, Ganz T, Nemeth E	Structure-function analysis of ferroportin defines the binding site and an alternative mechanism of action of hepcidin.	Blood 2018, 131: 899
Nonclassical ferroportin disease (FD) is a form of hereditary hemochromatosis caused by mutations in the iron transporter ferroportin (Fpn), resulting in parenchymal iron overload. Fpn is regulated by the hormone hepcidin, which induces Fpn endocytosis and cellular iron retention. We characterized 11 clinically relevant and 5 nonclinical Fpn mutations using stably transfected, inducible isogenic cell lines. All clinical mutants were functionally resistant to hepcidin as a consequence of either impaired hepcidin binding or impaired hepcidin-dependent ubiquitination despite intact hepcidin binding. Mapping the residues onto 2 computational models of the human Fpn structure indicated that (1) mutations that caused ubiquitination-resistance were positioned at helix-helix interfaces, likely preventing the hepcidin-induced conformational change, (2) hepcidin binding occurred within the central cavity of Fpn, (3) hepcidin interacted with up to 4 helices, and (4) hepcidin binding should occlude Fpn and interfere with iron export independently of endocytosis. We experimentally confirmed hepcidin-mediated occlusion of Fpn in the absence of endocytosis in multiple cellular systems: HEK293 cells expressing an endocytosis-defective Fpn mutant (K8R), oocytes expressing wild-type or K8R Fpn, and mature human red blood cells. We conclude that nonclassical FD is caused by Fpn mutations that decrease hepcidin binding or hinder conformational changes required for ubiquitination and endocytosis of Fpn. The newly documented ability of hepcidin and its agonists to occlude iron transport may facilitate the development of broadly effective treatments for hereditary iron overload disorders.
Asmar L, Gehan E, Newton W, Webber B, Marsden H, van Unnik A, Hamoudi A, Shimada H, Tsokos M, Harms D	Agreement among and within groups of pathologists in the classification of rhabdomyosarcoma and related childhood sarcomas. Report of an international study of four pathology classifications.	Cancer 1994, 74: 2579
Aspesi A, Betti M, Sculco M, Actis C, Olgasi C, Wlodarski MW, Vlachos A, Lipton JM, Ramenghi U, Santoro C, Follenzi A, Ellis SR, Dianzani I	A functional assay for the clinical annotation of genetic variants of uncertain significance in Diamond-Blackfan anemia.	Human mutation 2018, 39: 1102
Diamond-Blackfan anemia (DBA) is a rare genetic hypoplasia of erythroid progenitors characterized by mild to severe anemia and associated with congenital malformations. Clinical manifestations in DBA patients are quite variable and genetic testing has become a critical factor in establishing a diagnosis of DBA. The majority of DBA cases are due to heterozygous loss-of-function mutations in ribosomal protein (RP) genes. Causative mutations are fairly straightforward to identify in the case of large deletions and frameshift and nonsense mutations found early in a protein coding sequence, but diagnosis becomes more challenging in the case of missense mutations and small in-frame indels. Our group recently characterized the phenotype of lymphoblastoid cell lines established from DBA patients with pathogenic lesions in RPS19 and observed that defective pre-rRNA processing, a hallmark of the disease, was rescued by lentiviral vectors expressing wild-type RPS19. Here, we use this complementation assay to determine whether RPS19 variants of unknown significance are capable of rescuing pre-rRNA processing defects in these lymphoblastoid cells as a means of assessing the effects of these sequence changes on the function of the RPS19 protein. This approach will be useful in differentiating pathogenic mutations from benign polymorphisms in identifying causative genes in DBA patients.
Attarbaschi A, Mann G, Dworzak M, Trebo M, Muhlegger N, Reiter A, Horcher E, Gadner H	The role of surgery in the treatment of pediatric B-cell non-Hodgkin's lymphoma.	J Pediatr Surg 2002, 37: 1470
Attarbaschi A, Mann G, Dworzak M, Trebo M, Urban C, Fink F, Horcher E, Reiter A, Riehm H, Gadner H	Malignant non-Hodgkin's lymphoma of childhood and adolescence in Austria--therapy results between 1986 and 2000.	Wien Klin Wochenschr 2002, 114: 978
Attarbaschi A, Mann G, Dworzak M, Wiesbauer P, Schrappe M, Gadner H	Mediastinal mass in childhood T-cell acute lymphoblastic leukemia.	Med Pediatr Oncol 2002, 39: 558
Attarbaschi A, Dworzak M, Steiner M, Urban C, Fink F, Reiter A, Gadner H, Mann G	Outcome of children with primary resistant or relapsed non-Hodgkin lymphoma and mature B-cell leukemia after intensive first-line treatment: a population-based analysis of the Austrian Cooperative Study Group.	Pediatr Blood Cancer 2005, 44: 70
Attiyeh EF, London WB, Mossé YP, Wang Q, Winter C, Khazi D, McGrady PW, Seeger RC, Look AT, Shimada H, Brodeur GM, Cohn SL, Matthay KK, Maris JM, Children's Oncology Group	Chromosome 1p and 11q deletions and outcome in neuroblastoma.	The New England journal of medicine 2005 Nov 24; 353: 2243
Neuroblastoma is a childhood cancer with considerable morbidity and mortality. Tumor-derived biomarkers may improve risk stratification.
Attarbaschi A, Mann G, Panzer-Grümayer R, Röttgers S, Steiner M, König M, Csinady E, Dworzak MN, Seidel M, Janousek D, Möricke A, Reichelt C, Harbott J, Schrappe M, Gadner H, Haas OA	Minimal residual disease values discriminate between low and high relapse risk in children with B-cell precursor acute lymphoblastic leukemia and an intrachromosomal amplification of chromosome 21: the Austrian and German acute lymphoblastic leukemia Berlin-Frankfurt-Münster (ALL-BFM) trials.	Journal of clinical oncology 2008, 26: 3046
PURPOSE: We aimed to identify relapse predictors in children with a B-cell precursor acute lymphoblastic leukemia (ALL) and an intrachromosomal amplification of chromosome 21 (iAMP21), a novel genetic entity associated with poor outcome. PATIENTS AND METHODS: We screened 1,625 patients who were enrolled onto the Austrian and German ALL-Berlin-Frankfurt-Münster (ALL-BFM) trials 86, 90, 95, and 2000 with ETV6/RUNX1-specific fluorescent in situ hybridization probes, and we identified 29 patient cases (2%) who had an iAMP21. Minimal residual disease (MRD) was quantified with clone-specific immunoglobulin and T-cell receptor gene rearrangements. RESULTS: Twenty-five patients were good responders to prednisone, and all achieved remission after induction therapy. Eleven patients experienced relapse, which included eight who experienced relapse after cessation of front-line therapy. Six-year event-free and overall survival rates were 37% +/- 14% and 66% +/- 11%, respectively. Results of MRD analysis were available in 24 (83%) of 29 patients: nine (37.5%) belonged to the low-risk, 14 (58.5%) to the intermediate-risk, and one (4%) to the high-risk group. MRD results were available in 8 of 11 patients who experienced a relapse. Seven occurred among the 14 intermediate-risk patients, and one occurred in the high-risk patient. CONCLUSION: The overall and early relapse rates in the BFM study were lower than that in a previous United Kingdom Medical Research Council/Childhood Leukemia Working Party study (38% v 61% and 27% v 47%, respectively), which might result from more intensive induction and early reintensification therapy in the ALL-BFM protocols. MRD values were the only reliable parameter to discriminate between a low and high risk of relapse (P = .02).
Attarbaschi A, Panzer-Grümayer R, Mann G, Möricke A, König M, Mecklenbräuker A, Teigler-Schlegel A, Bradtke J, Harbott J, Göhring G, Stanulla M, Schrappe M, Zimmermann M, Haas OA, Austrian and German ALL-BFM (Berlin-Frankfurt-Münster) Study Group	Minimal residual disease-based treatment is adequate for relapse-prone childhood acute lymphoblastic leukemia with an intrachromosomal amplification of chromosome 21: the experience of the ALL-BFM 2000 trial.	Klinische Padiatrie 2014, 226(6-7): 338
Recently, the UK CCLG and COG reported that an intrachromosomal amplification of chromosome 21 (iAMP21) in acute lymphoblastic leukemia (ALL) loses its adverse prognostic impact with intensified therapy.
Attarbaschi A, Carraro E, Abla O, Barzilai-Birenboim S, Bomken S, Brugieres L, Bubanska E, Burkhardt B, Chiang AK, Csoka M, Fedorova A, Jazbec J, Kabickova E, Krenova Z, Lazic J, Loeffen J, Mann G, Niggli F, Miakova N, Osumi T, Ronceray L, Uyttebroeck A, Williams D, Woessmann W, Wrobel G, Pillon M, European Intergroup for Childhood Non-Hodgkin Lymphoma (EICNHL) and the International Berlin-Frankfurt-Münster (i-BFM) Study Group	Non-Hodgkin lymphoma and pre-existing conditions: spectrum, clinical characteristics and outcome in 213 children and adolescents.	Haematologica 2016, 101: 1581
Children and adolescents with pre-existing conditions such as DNA repair defects or other primary immunodeficiencies have an increased risk of non-Hodgkin lymphoma. However, large-scale data on patients with non-Hodgkin lymphoma and their entire spectrum of pre-existing conditions are scarce. A retrospective multinational study was conducted by means of questionnaires sent out to the national study groups or centers, by the two largest consortia in childhood non-Hodgkin lymphoma, the European Intergroup for Childhood non-Hodgkin Lymphoma, and the international Berlin-Frankfurt-Münster Study Group. The study identified 213 patients with non-Hodgkin lymphoma and a pre-existing condition. Four subcategories were established: a) cancer predisposition syndromes (n=124, 58%); b) primary immunodeficiencies not further specified (n=27, 13%); c) genetic diseases with no increased cancer risk (n=40, 19%); and d) non-classifiable conditions (n=22, 10%). Seventy-nine of 124 (64%) cancer predispositions were reported in groups with more than 20 patients: ataxia telangiectasia (n=32), Nijmegen breakage syndrome (n=26), constitutional mismatch repair deficiency (n=21). For the 151 patients with a known cancer risk, 5-year event-free survival and overall survival rates were 40%±4% and 51%±4%, respectively. Five-year cumulative incidences of progression/relapse and treatment-related death as a first event were 22%±4% and 24%±4%, respectively. Ten-year incidence of second malignancy was 24%±5% and 7-year overall survival of the 21 patients with a second malignancy was 41%±11%. Patients with non-Hodgkin lymphoma and pre-existing conditions have an inferior survival rate with a large proportion of therapy-related deaths compared to patients with non-Hodgkin lymphoma and no pre-existing conditions. They may require special vigilance when receiving standard or modified/reduced-intensity chemotherapy or when undergoing allogeneic stem cell transplantation.
Attarbaschi A, Mann G, Zimmermann M, Bader P, Barisone E, Basso G, Biondi A, Cario G, Cazzaniga G, Colombini A, Flotho C, Kuhlen M, Lang P, Lauten M, Linderkamp C, Locatelli F, Lo Nigro L, Moericke A, Niggli F, Panzer-Gruemayer R, Parasole R, Peters C, Caterina Putti M, Rizzari C, Suttorp M, Valsecchi MG, Conter V, Schrappe M, on behalf of the AIEOP-BFM (Associazione Italiana di Ematologia e Oncologia Pediatrica & Berlin-Frankfurt-Muenster) Study Group	Randomized post-induction and delayed intensification therapy in high-risk pediatric acute lymphoblastic leukemia: long-term results of the international AIEOP-BFM ALL 2000 trial.	Leukemia 2019 Dec 5;
Attarbaschi A, Möricke A, Harrison CJ, Mann G, Baruchel A, De Moerloose B, Conter V, Devidas M, Elitzur S, Escherich G, Hunger SP, Horibe K, Manabe A, Loh ML, Pieters R, Schmiegelow K, Silverman LB, Stary J, Vora A, Pui CH, Schrappe M, Zimmermann M, Ponte-di-Legno Childhood Acute Lymphoblastic Leukemia Working Group	Outcomes of Childhood Noninfant Acute Lymphoblastic Leukemia With 11q23/KMT2A Rearrangements in a Modern Therapy Era: A Retrospective International Study.	Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2023, 41: 1404
We aimed to study prognostic factors and efficacy of allogeneic hematopoietic stem-cell transplantation (allo-HSCT) in first remission of patients with noninfant childhood acute lymphoblastic leukemia (ALL) with 11q23/ rearrangements treated with chemotherapy regimens between 1995 and 2010.
Attiyeh EF, London WB, Mossé YP, Wang Q, Winter C, Khazi D, McGrady PW, Seeger RC, Look AT, Shimada H, Brodeur GM, Cohn SL, Matthay KK, Maris JM, Children's Oncology Group	Chromosome 1p and 11q deletions and outcome in neuroblastoma.	The New England journal of medicine 2005 Nov 24; 353: 2243
Neuroblastoma is a childhood cancer with considerable morbidity and mortality. Tumor-derived biomarkers may improve risk stratification.
Auerbach AD	Fanconi anemia and its diagnosis.	Mutat Res 2009, 668(1-2): 4
Fanconi anemia (FA) is a genetically and phenotypically heterogeneous recessive disorder characterized by diverse congenital malformations, progressive pancytopenia, and predisposition to both hematologic malignancies and solid tumors. Congenital anomalies vary from patient to patient and may affect skeletal morphogenesis as well as any of the major organ systems. Although this highly variable phenotype makes accurate diagnosis on the basis of clinical manifestations difficult in some patients, laboratory study of chromosomal breakage induced by diepoxybutane (DEB) or other crosslinking agents provides a unique cellular marker for the diagnosis of the disorder either prenatally or postnatally. Diagnosis based on abnormal response to DNA crosslinking agents can be used to identify the pre-anemia patient as well as patients with aplastic anemia or leukemia who may or may not have the physical stigmata associated with the syndrome. This overview will present our current knowledge regarding the varied phenotypic manifestations of FA and procedures for diagnosis based upon abnormal DNA damage responses.
Au-Yeung RKH, Richter J, Iaccarino I, Abramov D, Bacon CM, Balagué O, d'Amore ESG, Simonitsch-Klupp I, Hebeda K, Nakazawa A, Oschlies I, Kontny U, Woessmann W, Burkhardt B, Klapper W	Molecular features of non-anaplastic peripheral T-cell lymphoma in children and adolescents.	Pediatric blood & cancer 2021, 68:e29285
Non-anaplasticperipheral T-cell lymphomas (PTCL) are rare tumors in children, adolescents, and young adults (CAYA) with poor prognosis and scarce genetic data. We analyzed lymphoma tissue from 36 patients up to 18 years old with PTCL, not otherwise specified (PTCL-NOS), hepatosplenic T-cell lymphoma, Epstein-Barr virus (EBV)-positive T-lymphoproliferative diseases, subcutaneous panniculitis-like T-cell lymphoma, and other PTCL types. Twenty-three patients (64%) had at least one genetic variant detectable, including TET2, KMT2C, PIK3D, and DMNT3A. TP53 and RHOA variants, commonly found in adults, were not identified. Eight of 20 (40%) CAYA PTCL-NOS had no detectable mutations. The genetic findings suggest that CAYA PTCL differ from adult cases.
Au-Yeung RKH, Richter J, Iaccarino I, Abramov D, Bacon CM, Balagué O, d'Amore ESG, Simonitsch-Klupp I, Hebeda K, Nakazawa A, Oschlies I, Kontny U, Woessmann W, Burkhardt B, Klapper W	Molecular features of non-anaplastic peripheral T-cell lymphoma in children and adolescents.	Pediatric blood & cancer 2021, 68:e29285
Non-anaplasticperipheral T-cell lymphomas (PTCL) are rare tumors in children, adolescents, and young adults (CAYA) with poor prognosis and scarce genetic data. We analyzed lymphoma tissue from 36 patients up to 18 years old with PTCL, not otherwise specified (PTCL-NOS), hepatosplenic T-cell lymphoma, Epstein-Barr virus (EBV)-positive T-lymphoproliferative diseases, subcutaneous panniculitis-like T-cell lymphoma, and other PTCL types. Twenty-three patients (64%) had at least one genetic variant detectable, including TET2, KMT2C, PIK3D, and DMNT3A. TP53 and RHOA variants, commonly found in adults, were not identified. Eight of 20 (40%) CAYA PTCL-NOS had no detectable mutations. The genetic findings suggest that CAYA PTCL differ from adult cases.
Au-Yeung RKH, Padilla LA, Zimmermann M, Reinke S, Oschlies I, Escherich G, Woessmann W, Burkhardt B, Klapper W	Frequency and prognostic implications of KMT2A rearrangements in children with precursor B-cell lymphoma.	Leukemia 2023, 37: 488
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