Literatur

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

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Autor(en)	Titel	Quelle
Wabitsch M, Kunze D (federführend für die AGA)	Konsensbasierte (S2) Leitlinie zur Diagnostik, Therapie und Prävention von Übergewicht und Adipositas im Kindes- und Jugendalter.	Version 15.10.2015, www.a-g-a.de
Wachtel M, Dettling M, Koscielniak E, Stegmaier S, Treuner J, Simon-Klingenstein K, Buhlmann P, Niggli F, Schafer B	Gene expression signatures identify rhabdomyosarcoma subtypes and detect a novel t(2;2)(q35;p23) translocation fusing PAX3 to NCOA1.	Cancer Res 2004, 64: 5539
Wachtel M, Runge T, Leuschner I, Stegmaier S, Koscielniak E, Treuner J, Odermatt B, Behnke S, Niggli FK, Schäfer BW	Subtype and prognostic classification of rhabdomyosarcoma by immunohistochemistry.	Journal of clinical oncology 2006, 24: 816
PURPOSE: Rhabdomyosarcoma (RMS) is classified into two main subgroups: the embryonal (ERMS) and the alveolar (ARMS) form. The majority of the ARMSs are associated with specific chromosomal translocations (pARMS). Because ARMS is much more aggressive than ERMS, RMS subclassification has clinical relevance. However, diagnosis of RMS subgroups on the basis of histology or molecular biology can be difficult, and supplementing diagnostic methods would be desirable. The aim of this study was to establish a panel of markers for RMS subgroup classification by immunohistochemistry. MATERIALS AND METHODS: Gene expression data were used for selection of subgroup-specific markers. Single sections of RMS with available expression data were used for establishment of the immunohistochemistry. Evaluation of the sensitivity and specificity of the markers was carried out using a tissue array representing 252 RMSs. Kaplan-Meier survival curves were calculated for determination of differences in overall survival of the different staining subgroups. RESULTS: AP2beta and P-cadherin were selected as markers for pARMS, and epidermal growth factor receptor (EGFR) and fibrillin-2 as markers for ERMS. EGFR + fibrillin-2 detected ERMS with a specificity of 90% and with a sensitivity of 60%. AP2beta + P-cadherin detected pARMS with a specificity of 98% and a sensitivity of 64%, and allowed the detection of several misclassified tumors. The EGFR + fibrillin-2-positive group is associated with a favorable outcome, and the AP2beta + P-cadherin-positive group is associated with an unfavorable outcome. CONCLUSION: The presented set of marker proteins detects RMS subgroups with high specificity and may be useful in routine subtype classification of RMS.
Wachowiak J, Sykora KW, Cornish J, Chybicka A, Kowalczyk JR, Gorczyńska E, Choma M, Grund G, Peters C	Treosulfan-based preparative regimens for allo-HSCT in childhood hematological malignancies: a retrospective study on behalf of the EBMT pediatric diseases working party.	Bone Marrow Transplant 2011, Epub ahead of print
This retrospective analysis evaluated 51 children (0.7-17 years; median eight) with high-risk or advanced hematological malignancies, including 18 (35%) patients undergoing second/third hematopoietic SCT (allo-HSCT), not eligible for standard myeloablative regimens and transplanted from matched sibling (MSD) (n=24) or matched unrelated (MUD) (n=27) donors. Preparative regimens were based on treosulfan (TREO) i.v., a structural analog of BU, given at total dose of 30 g/m(2) (n=21) or 36-42 g/m(2) (n=30) in combination with, fludarabine, cyclophosphamide, melphalan and/or VP-16 according to diagnosis, and risk factors. Deaths due to early regimen-related toxicity (RRT) did not occur. Nonrelapse mortality was 8% at 1 year and 16% after 4 years. Myeloid engraftment was achieved in 94%, complete donor chimerism in 90% of patients. A 4-year incidence of relapse was 24%, and was significantly lower after MUD-HSCT (8%) than after MSD-HSCT (39%), but similar in children undergoing first (28%) or second/third HSCT (17%). A 4-year disease-free survival was 61%, but it was significantly better in myeloid (73%), than in lymphoid malignancies (41%). Thus, children with high-risk and advanced hematological malignancies and high-risk of life-threatening RRT can be transplanted effectively and safely using TREO-based regimens. Particularly favorable results were achieved in myeloid malignancies and in children undergoing second HSCT.Bone Marrow Transplantation advance online publication, 7 February 2011; doi:10.1038/bmt.2010.343
Wagner HJ, Schlager F, Claviez A, Bucsky P	Detection of Epstein-Barr virus DNA in peripheral blood of paediatric patients with Hodgkin's disease by real-time polymerase chain reaction.	Eur J Cancer 2001, 37: 1853
Wagner S, Sörensen N, Kortmann RD, Gnekow A, Kühl J, Wolff JEA	HIT-GBM data bank: Overall survival in relation to extent to resection; SIOP XXXIV Meeting, Porto, Portugal.	Medical and Pediatric Oncology 2002, 39 : 242
Wagner S	Therapie von hochgradig malignen Gliomen im Kindes- und Jugendalter.	WIR Informationsschrift der Aktion für krebskranke Kinder e.V. (Bonn) 2003, 1: 13
Wagner-Bohn A, Henze G, von Stackelberg A, Boos J	Phase II study of gemcitabine in children with relapsed leukemia.	Pediatric blood & cancer 2006, 46: 262
Wagner S, Benesch M, Berthold F, Gnekow AK, Rutkowski S, Sträter R, Warmuth-Metz M, Kortmann RD, Pietsch T, Wolff JE	Secondary dissemination in children with high-grade malignant gliomas and diffuse intrinsic pontine gliomas.	Br J Cancer 95: 991
In children, treatment regimen for high-grade gliomas (HGG) and diffuse intrinsic pontine gliomas (DIPG) are generally not stratified according to disease stage. The hypothesis was that secondary disseminating disease (SDD) in children with HGG is related to an even worse outcome. Description of SDD pattern was performed. In total, 270 children with newly diagnosed HGG or DIPG were eligible for retrospective analysis of SDD. Medical and computer records of these patients were reviewed for demographic characteristics, sites of dissemination, prognostic variables. Forty-six (17%) of the 270 patients had developed SDD. The median time to SDD was 8.2 months. The median overall survival (OS) after dissemination was 3.2 months. The SDD was located parenchymal in the supratentorial (34.8%), infratentorial (6.5%), supratentorial and infratentorial (19.6%), spinal (10.9%), spinal and cerebral (6.5%) regions of the CNS, or leptomeningeal (21.7%). For HGG patients, the median OS was shorter among patients with SDD than among patients without SDD (1.02 vs 1.41 years, P=0.0495). In the group of patients with SDD, patients with cerebrospinal fluid dissemination had a worse outcome compared with patients with parenchymal metastases. Summarising, SDD is a negative prognostic factor for patients with HGG outside the pons. Treatment stratification should be considered.
Wagner LM, McAllister N, Goldsby RE, Rausen AR, McNall-Knapp RY, McCarville MB, Albritton K	Temozolomide and intravenous irinotecan for treatment of advanced Ewing sarcoma.	Pediatric blood & cancer 2007, 48: 132
Wagner JE, Eapen M, MacMillan ML, Harris RE, Pasquini R, Boulad F, Zhang MJ, Auerbach AD	Unrelated donor bone marrow transplantation for the treatment of Fanconi anemia.	Blood 2007, 109: 2256
Bone marrow transplantation (BMT) is the only known cure for the hematologic manifestations of Fanconi anemia (FA). Potential benefits of unrelated donor BMT for FA, however, have been severely limited by graft rejection and treatment-related mortality with resultant poor survival. Therefore, we evaluated the impact of potential prognostic factors on hematopoietic recovery, graft-versus-host disease (GVHD), and mortality in 98 recipients of unrelated donor BMT who received transplants between 1990 and 2003. Probabilities of neutrophil (89% vs 69%; P = .02) and platelet (74% vs 23%; P < .001) recovery were higher after fludarabine-containing regimens than nonfludarabine-containing regimens. Risks of acute GVHD (relative risk [RR], 4.29; P < .001) were higher with non-T-cell-depleted grafts. The day-100 mortality rate was significantly higher after nonfludarabine-containing regimens than fludarabine-containing regimens (65% vs 24%, respectively; P < .001). Corresponding 3-year adjusted overall survival rates were 13% versus 52% (P < .001). In addition, mortality was higher in recipients who were older (> 10 years), who were cytomegalovirus (CMV) seropositive, and who received more than 20 blood product transfusions before BMT. Based on these results, significant practice changes are suggested: use of a fludarabine-containing conditioning regimen in the context of T-cell-depleted marrow allografts, and earlier referral for transplantation prior to excessive transfusions in patients with marrow failure.
Wagner AE, Schwarzmayr T, Häberle B, Vokuhl C, Schmid I, Kaller M, Hermeking H, von Schweinitz D, Kappler R	Erratum: Wagner, A. E, et al. SP8 Promotes an Aggressive Phenotype in Hepatoblastoma via FGF8 Activation. Cancers 2020, 12, 2294.	Cancers 2021, 13
Two contributors' names were missing in the original version of the authorship of the paper [...].
Wahn V, Aberer W, Eberl W, Faßhauer M, Kühne T, Kurnik K, Magerl M, Meyer-Olson D, Martinez-Saguer I, Späth P, Staubach-Renz P, Kreuz W	Hereditary angioedema (HAE) in children and adolescents--a consensus on therapeutic strategies.	European journal of pediatrics 2012, 171: 1339
Hereditary angioedema due to C1 inhibitor (C1 esterase inhibitor) deficiency (types I and II HAE-C1-INH) is a rare disease that usually presents during childhood or adolescence with intermittent episodes of potentially life-threatening angioedema. Diagnosis as early as possible is important to avoid ineffective therapies and to properly treat swelling attacks. At a consensus meeting in June 2011, pediatricians and dermatologists from Germany, Austria, and Switzerland reviewed the currently available literature, including published international consensus recommendations for HAE therapy across all age groups. Published recommendations cannot be unconditionally adopted for pediatric patients in German-speaking countries given the current approval status of HAE drugs. This article provides an overview and discusses drugs available for HAE therapy, their approval status, and study results obtained in adult and pediatric patients. Recommendations for developing appropriate treatment strategies in the management of HAE in pediatric patients in German-speaking countries are provided.Conclusion Currently, plasma-derived C1 inhibitor concentrate is considered the best available option for the treatment of acute HAE-C1-INH attacks in pediatric patients in German-speaking countries, as well as for short-term and long-term prophylaxis.
Wahn V, Aberer W, Aygören-Pürsün E, Bork K, Eberl W, Faßhauer M, Krüger R, Magerl M, Martinez-Saguer I, SpÃ¤th P, Staubach-Renz P, Weber-Chrysochoou C	Hereditary angioedema in children and adolescents - A consensus update on therapeutic strategies for German-speaking countries.	Pediatric allergy and immunology 2020, Epup ahead of print
At a consensus meeting in August 2018, pediatricians and dermatologists from German-speaking countries discussed the therapeutic strategy for the treatment of pediatric patients with types I and II hereditary angioedema due to C1 inhibitor deficiency (HAE-C1-INH) for Germany, Austria, and Switzerland, taking into account the current marketing approval status. HAE-C1-INH is a rare disease that usually presents during childhood or adolescence with intermittent episodes of potentially life-threatening angioedema. Diagnosis as early as possible and an optimal management of the disease are important to avoid ineffective therapies and to properly treat swelling attacks. This article provides recommendations for developing appropriate treatment strategies in the management of HAE-C1-INH in pediatric patients in German-speaking countries. An overview of available drugs in this age group is provided, together with their approval status, and study results obtained in adults and pediatric patients.
Walter O, Cougoul P, Maquet J, Bartolucci P, Lapeyre-Mestre M, Lafaurie M, Moulis G	Risk of vaso-occlusive episode after exposure to corticosteroids in patients with sickle cell disease.	Blood 2022, 139: 3771
Vaso-occlusive episodes (VOEs) are a major concern in patients with sickle cell disease (SCD). Exposure to systemic corticosteroids has been suspected to increase the occurrence of VOEs in case reports or series. No comparative study has been conducted to investigate this risk, which is still debated. Several clinical trials demonstrated the effectiveness of corticosteroids for the treatment of VOEs, but with increased rates of readmission. The aim of the study was to assess the risk of hospitalization for VOE associated with exposure to systemic corticosteroids in patients with SCD. We used a case-case-time-control design in a nationwide population-based cohort built in the French national health insurance database between 2010 and 2018. The population included all patients with SCD with at least 1 hospitalization for VOE. Corticosteroids were identified using out-of-hospital dispensing data. The outcome was the first hospitalization for VOE. The case-case-time-control design induces self-adjustment for time-invariant confounders, including genotype. Analyses were adjusted for time-dependent confounders (infections, red blood transfusions) and stratified by exposure to hydroxyurea. Overall, 5151 patients were included in the main analysis. Corticosteroid exposure was significantly associated with the occurrence of hospitalizations for VOEs: adjusted odds ratio, 3.8; 95% confidence interval [CI], 2.4-5.6). In patients exposed to hydroxyurea, the adjusted odds ratio was 2.6 (95% CI, 1.1-6.4); it was 4.0 (95% CI, 2.5-6.3) in unexposed patients. These results were consistent in children and adults. In conclusion, systemic corticosteroids were associated to an increased risk of hospitalization for VOEs and should be limited in patients with SCD.
Sharpe CC, Suddle A, Stuart-Smith S	An Overview of Solid Organ Transplantation in Patients With Sickle Cell Disease.	Transplantation 2023, 107: 596
Sickle cell disease is a common genetic disorder affecting >300 000 people across the world. The vast majority of patients cared for in high-resource settings live well into adulthood, but many develop a high burden of disease complications. Good standard of care including disease-modifying agents and transfusion programs limits the number of patients who develop end-stage organ disease, but for those that do, the prognosis can be very poor. Solid organ transplantation is a well-established mode of treatment for patients with sickle cell disease and kidney or liver failure, but appropriate patient selection and perioperative management are important for achieving good outcomes. Hematopoietic stem cell transplantation and gene therapy may offer novel treatment options for adult patients with chronic organ damage in the future, but these are not yet widely available. For now, good, holistic care and early intervention of end-organ complications can minimize the number of patients requiring solid organ transplantation later in life.
Wang JL, Huang LT, Wu KH, Lin HW, Ho MY, Liu HE	Associations of reactive thrombocytosis with clinical characteristics in pediatric diseases.	Pediatrics and neonatology 2011t; 52: 261
Reactive thrombocytosis (RT) in pediatric patients is common, but usually without symptoms. The incidence of RT is different depending on age. Mostly, we reason that RT is a phenomenon, nevertheless the diagnostic value of RT is little known. Therefore, the aim of this study was to determine the association of RT and clinical or laboratory characteristics in pediatric diseases.
Warrell RP Jr, Frankel SR, Miller WH Jr, Scheinberg DA, Itri LM, Hittelman WN, Vyas R, Andreeff M, Tafuri A, Jakubowski A et al.	Differentiation therapy of acute promyelocytic leukemia with tretinoin (all-trans-retinoic acid).	N Engl J Med 1991, 324: 1385
Wargalla-Plate U, Hero B, Berthold F	Neuroblastoma.	Schweiz Rundsch Med Prax 1995, 84: 1152
Warmann S, Fuchs J, Wilkens L, Gratz K, von Schweinitz D, Mildenberger H	Successful therapy of subcutaneously growing human hepatoblastoma xenografts with topotecan.	Med Pediatr Oncol 2001, 37: 449
Warmuth-Metz M, Kühl J	Neuroradiological differential diagnosis in medulloblastomas and ependymomas.	Klin Pädiatr 2002, 214: 162
Warmuth-Metz M, Kühl J, Rutkowski S, Krauss J, Solymosi L	Differential infratentorial brain tumor diagnosis in children.	Radiologe 2003, 43: 977
Warmuth-Metz M, Kühl J, Krauss J, Solymosi L	Subdural enhancement on postoperative spinal MRI after resection of posterior cranial fossa tumours.	Neuroradiology 2004, 46: 219
Warmuth-Metz M, Gnekow AK, Muller H, Solymosi L	Differential diagnosis of suprasellar tumors in children.	Klinische Padiatrie 2004, 216: 323
In contrary to the adult age the most common suprasellar tumors in children are with decreasing frequency craniopharyngiomas, chiasmatic/hypothalamic low-grade gliomas, germinomas and lesions attributable to a Langerhans cell histiocytosis. For differential diagnostic purposes also the rare hypothalamic hamartoma and meningeal metastases in the infundibular recess of the third ventricle are included. The typical aspects of the various tumors on computed tomography (CT) and magnetic resonance imaging (MRI) together with important clinical differences are illustrated. On the basis of imaging results and clinical symptoms differential diagnosis between the various tumor entities should be feasible in many cases. Of course, only in strictly defined cases like typical chiasmatic/hypothalamic and optic pathway gliomas or bilocular germ cell tumors a histological confirmation is dispensable.
Warmuth-Metz M, Blashofer S, von Bueren AO, von Hoff K, Bison B, Pohl F, Kortmann RD, Pietsch T, Rutkowski S	Recurrence in childhood medulloblastoma.	J Neurooncol 2010, Epub ahead of print]
Thirty-eight consecutive children treated according to the HIT2000 and HIT91 studies for medulloblastoma who suffered 40 recurrence events were identified from a neuroradiological database. Relapse was associated with younger median age compared with all children treated on HIT2000. Eight patients relapsed with isolated local recurrence. There was no correlation with incomplete surgical removal or violation of the respective treatment protocol. Four patients were younger than 4 years at time of initial presentation and thus were not treated primarily with radiotherapy, suggesting that delayed radiotherapy might be a contributing factor. Meningeal dissemination was present in 32 events; 16 were located in the frontal region, 8 of which were isolated nodular frontal and frontobasal meningeal disease. Circumscribed meningeal recurrences were associated with better overall survival (OS) compared with diffuse, widespread recurrences. Isolated frontobasal meningeal relapses are a well-known phenomenon in medulloblastomas even years after treatment and have been correlated to an underdose of radiation in many literature reports. However, in our patients there was no correlation to possible treatment violations, indicating that inadequate radiation dose to the frontobasal region was unlikely to be a causative factor. Surgical technique varied due to the multicentric nature of our study, so position during surgery was not recognized as a predisposing factor for frontobasal recurrence.
Warmann SW, Nourkami N, Frühwald M, Leuschner I, Schenk JP, Fuchs J, Graf N	Primary Lung Metastases in Pediatric Malignant Non-Wilms Renal Tumors: Data from SIOP 93-01/GPOH and SIOP 2001/GPOH.	Klinische Padiatrie 2012, 224: 148
Malignant non-Wilms renal tumors (NWRT) are a small but relevant subgroup of renal neoplasms in children. In this study we analyzed corresponding data from the trials SIOP 93-01/GPOH and SIOP 2001/GPOH of the Society of Pediatric Oncology and Hematology.Data of 22 patients with NWRT and primary lung metastases were retrospectively reviewed. Analyses included epidemiology, tumor characteristics, chemotherapy, local treatment, and outcome.The following diagnoses were registered: Malignant Rhabdoid tumor of the kidney (MRTK, n=15), Renal-cell carcinoma (RCC, n=3), Clear-cell sarcoma of the kidney (CCSK, n=3), and primitive neuro ectodermal tumor (PNET, n=1). Median age of patients at diagnosis was 14 months. Overall survival was 36.36% (8/22). Of the 15 children with MRTK 3 survived, 3/3 patients with RCC, 1/3 patients with CCSK, and 1/1 patient with PNET survived. Lung metastases disappeared in 6 patients after initial chemotherapy, 6/8 patients undergoing local treatment of lung metastases (surgery, irradiation, or both) achieved complete remission. Only patients with complete clearance of lung lesions, either through neoadjuvant chemotherapy or subsequent local treatment, survived. Mean Follow up was 31 months (1-137).Survival of patients with stage IV NWRT is dismal. Complete removal of lung metastases seems mandatory for survival. An aggressive diagnostic and therapeutic approach seems justified in affected children.
Warmuth-Metz M, Bison B, Gerber NU, Pietsch T, Hasselblatt M, Frühwald MC	Bone Involvement in Atypical Teratoid/Rhabdoid Tumors of the CNS.	AJNR. American journal of neuroradiology 2013, Epub ahead of print
SUMMARY:Destruction of the bony structures of the skull is rare in primary tumors of the CNS. In low-grade gliomas, modeling of the skull is caused by slow growth and chronic pressure. Bony destruction is exceptional even in highly malignant gliomas. Atypical teratoid/rhabdoid tumors of the CNS are highly malignant neoplasms diagnosed with an increasing frequency, mainly in young children. On imaging, these tumors exhibit distinct though not specific morphologic features including peripheral cysts, bleeding residues, and a distinct bandlike, wavy pattern of enhancement. A combination of these single characteristics together with a predilection for young age is suggestive of an atypical teratoid/rhabdoid tumor. We present 5 children with an atypical teratoid/rhabdoid tumor affecting the adjacent bone. These 5 patients were collected in our imaging data base for childhood atypical teratoid/rhabdoid tumor consisting of 91 children at the time of this evaluation and thus representing 6.6%. The mean age of children with bone involvement (4.8 years) was above the average age (2 years) of all children in the data base. We add this rare feature to the list of typical features in MR imaging and CT morphology of atypical teratoid/rhabdoid tumor.
Ware RE	Hydroxycarbamide: Clinical aspects.	Comptes rendus biologies 2013, 336: 177
Due to its oral route of administration and mild toxicity profile, as well as its potent laboratory and clinical effects, hydroxyurea (or hydroxycarbamide) has been the primary focus of fetal hemoglobin (HbF) induction strategies for the treatment of children with sickle cell anemia (SCA). When administered orally once a day, hydroxyurea treatment is very well tolerated with little short-term toxicity. Hydroxyurea has documented laboratory efficacy with increases in Hb and HbF; treatment also significantly reduces the number of painful episodes, acute chest syndrome, transfusions, and hospitalizations. Most young patients reach a maximum tolerated dose of hydroxyurea at 25-30mg/kg/d, where they will achieve key laboratory thresholds (Hb≥9g/dL and HbF≥20%) without excessive myelosuppression. Potential long-term toxicities continue to be of great concern and should be monitored in all patients with SCA who receive hydroxyurea therapy. To date, however, no increases in stroke, myelodysplasia, or carcinogenicity have been detected in SCA patient cohorts, with drug exposure now reaching 15years for some treated children. Taken together, available evidence suggests that hydroxyurea represents an inexpensive and effective treatment option that should be offered to most, if not all, patients with SCA. As countries in Africa develop newborn screening programs to identify SCA, the widespread use of hydroxyurea may prove to be a useful treatment to help ameliorate the disease in resource-limited settings. Hydroxyurea is the only currently available disease-modifying therapy for SCA, and is emerging as a safe and effective treatment for all patients with SCA, in both developed and developing countries.
Warren AJ	Molecular basis of the human ribosomopathy Shwachman-Diamond syndrome.	Advances in biological regulation 2018, 67: 109
Wasilewski-Masker K, Seidel KD, Leisenring W, Mertens AC, Shnorhavorian M, Ritenour CW, Stovall M, Green DM, Sklar CA, Armstrong GT, Robison LL, Meacham LR	Male infertility in long-term survivors of pediatric cancer: a report from the childhood cancer survivor study.	Journal of cancer survivorship : research and practice 2014, 8: 437
The purpose of this study was to assess the prevalence of male infertility and treatment-related risk factors in childhood cancer survivors.
Wassef M, Blei F, Adams D, Alomari A, Baselga E, Berenstein A, Burrows P, Frieden IJ, Garzon MC, Lopez-Gutierrez JC, Lord DJ, Mitchel S, Powell J, Prendiville J, Vikkula M, ISSVA Board and Scientific Committee	Vascular Anomalies Classification: Recommendations From the International Society for the Study of Vascular Anomalies.	Pediatrics 2015, 136:e203
Weber R, Pietsch T, von Schweinitz D, Lichter P	Characterization of genomic alterations in hepatoblastomas. A role for gains on chromosomes 8q and 20 as predictors of poor outcome.	Am J Pathol 2000, 157: 571
Weber A, Taube S, Starke S, Bergmann E, Christiansen NM, Christiansen H	Detection of human tumor cells by amplicon fusion site polymerase chain reaction (AFS-PCR).	J Clin Invest 2011, 121: 545
Reliable diagnostic strategies for individuals with cancer demand practical methods for highly sensitive and specific detection of tumor cells. Amplification of genomic regions that include putative oncogenes is common in tumor cells of various types. Genomic array platforms offer the opportunity to identify and precisely map amplified genomic regions (ampGRs). The stable existence of these tumor cell–specific genomic aberrations during and after therapy, in theory, make ampGRs optimal targets for cancer diagnostics. In this study, we mapped ampGRs around the proto-oncogene MYCN of human neuroblastomas using a high-resolution tiling array (HR-TA). Based on the HR-TA data, we were able to precisely describe the telomeric and centromeric borders of the ampGRs and deduce virtual fusion sites of the joined ampGRs (amplicon fusion sites [AFSs]). These AFSs served as blueprints for the subsequent design of AFS bridging PCR assays (AFS-PCRs). Strikingly, these assays were absolutely tumor cell specific and capable of detecting 1 tumor cell in 1 × 10(6) to 8 × 10(6) control cells. We successfully proved the in vivo practicability of AFS-PCR by detecting and quantifying the specific AFS DNA of human MYCN-amplified neuroblastomas in the patients’ corresponding peripheral blood and bone marrow samples. Thus, we believe AFS-PCR could become a powerful and nevertheless feasible personalized diagnostic tool applicable to a large number of cancer patients, including children with MYCN-amplified neuroblastomas.
Weber ML, Schneider DT, Offenmüller S, Kaatsch P, Einsiedel HG, Benesch M, Claviez A, Ebinger M, Kramm C, Kratz C, Lawlor J, Leuschner I, Merkel S, Metzler M, Nustede R, Petsch S, Seeger KH, Schlegel PG, Suttorp M, Zolk O, Brecht IB	Pediatric Colorectal Carcinoma is Associated With Excellent Outcome in the Context of Cancer Predisposition Syndromes.	Pediatric blood & cancer 2016, 63: 611
Colorectal carcinoma (CRC) is the second most common adult cancer in Germany, however, it is extremely rare in children and adolescents. In these patients, previous literature describes aggressive behavior and diagnosis at advanced stage.
Wegert J, Vokuhl C, Ziegler B, Ernestus K, Leuschner I, FurtwÃ¤ngler R, Graf N, Gessler M	TP53 alterations in Wilms tumour represent progression events with strong intratumour heterogeneity that are closely linked but not limited to anaplasia.	The journal of pathology. Clinical research 2017, 3: 234
TP53 mutations have been associated with anaplasia in Wilms tumour, which conveys a high risk for relapse and fatal outcome. Nevertheless, TP53 alterations have been reported in no more than 60% of anaplastic tumours, and recent data have suggested their presence in tumours that do not fulfil the criteria for anaplasia, questioning the clinical utility of TP53 analysis. Therefore, we characterized the TP53 status in 84 fatal cases of Wilms tumour, irrespective of histological subtype. We identified TP53 alterations in at least 90% of fatal cases of anaplastic Wilms tumour, and even more when diffuse anaplasia was present, indicating a very strong if not absolute coupling between anaplasia and deregulation of p53 function. Unfortunately, TP53 mutations do not provide additional predictive value in anaplastic tumours since the same mutation rate was found in a cohort of non-fatal anaplastic tumours. When classified according to tumour stage, patients with stage I diffuse anaplastic tumours still had a high chance of survival (87%), but this rate dropped to 26% for stages II-IV. Thus, volume of anaplasia or possible spread may turn out to be critical parameters. Importantly, among non-anaplastic fatal tumours, 26% had TP53 alterations, indicating that TP53 screening may identify additional cases at risk. Several of these non-anaplastic tumours fulfilled some criteria for anaplasia, for example nuclear unrest, suggesting that such partial phenotypes should be under special scrutiny to enhance detection of high-risk tumours via TP53 screening. A major drawback is that these alterations are secondary changes that occur only later in tumour development, leading to striking intratumour heterogeneity that requires multiple biopsies and analysis guided by histological criteria. In conclusion, we found a very close correlation between histological signs of anaplasia and TP53 alterations. The latter may precede development of anaplasia and thereby provide diagnostic value pointing towards aggressive disease.
Wegehaupt O, Wustrau K, Lehmberg K, Ehl S	Cell Versus Cytokine - Directed Therapies for Hemophagocytic Lymphohistiocytosis (HLH) in Inborn Errors of Immunity.	Frontiers in immunology 2020, 11: 808
Hemophagocytic lymphohistiocytosis (HLH) is a heterogeneous hyperinflammatory syndrome with different pathways of pathogenesis resulting in similar clinical presentations. It is best defined and understood if presenting in the context of genetic immunodeficiencies associated with defects of lymphocyte cytotoxicity. In these "primary" forms of HLH, cellular and soluble immune effectors are relatively well characterized. While etoposide-based broad cell-directed therapies remain standard of care, more specific therapies targeting these effectors individually are increasingly available. Anti-CD52 as a cell-directed therapy and anti-IFN-gamma, IL-18BP, and JAK-inhibition as cytokine-directed therapies are expected to broaden the therapeutic options, but the precise role of these drugs in first-line and rescue treatment indications remains to be defined. A number of additional inborn errors of immunity are associated with episodes of immune activation fulfilling the clinical criteria of HLH. Impaired pathogen control is a key driver of hyperinflammation in some conditions, while others are characterized by a strong autoinflammatory component. This heterogeneity of disease-driving factors and the variable severity in disease progression in these conditions do not allow a simple adaptation of protocols established for "primary" HLH to HLH in the context of other inborn errors of immunity. Cytokine-directed therapies hold significant promise in these increasingly recognized disorders.
Weh H, Kuse R, Hoffmann R, Seeger D, Suciu S, Kabisch H, Ritter J, Hossfeld D	Prognostic significance of chromosome analysis in de novo acute myeloid leukemia (AML).	Blut 1988, 56: 19
Weh H, Hoffmann R, Suciu S, Ritter J, Kuse K, Hossfeld D	Prognostic significance of chromosome analysis in de novo acute myeloid leucemia.	Haematology and Blood Transfusion 1990, 33: 150
Weirich A, Ludwig R	Das Nephroblastom - Diagnose, Therapie und Prognose.	Nierentumoren 1997
Weirich A, Leuschner I, Harms D, Vujanic G, Troger J, Abel U, Graf N, Schmidt D, Ludwig R, Voute P	Clinical impact of histologic subtypes in localized non-anaplastic nephroblastoma treated according to the trial and study SIOP-9/GPOH.	Ann Oncol 2001, 12: 311
Weidner R, Pollmann S, Muller H, von Cramon D	Top-down controlled visual dimension weighting.	Cereb Cortex 2002, 12: 318
Weirich A, Ludwig R, Graf N, Abel U, Leuschner I, Vujanic G, Mehls O, Boos J, Beck J, Royer-Pokora B, Voute P	Survival in nephroblastoma treated according to the trial and study SIOP-9/GPOH with respect to relapse and morbidity.	Ann Oncol 2004, 15: 808
Wei JS, Greer BT, Westermann F, Steinberg SM, Son CG, Chen QR, Whiteford CC, Bilke S, Krasnoselsky AL, Cenacchi N, Catchpoole D, Berthold F, Schwab M, Khan J	Prediction of clinical outcome using gene expression profiling and artificial neural networks for patients with neuroblastoma.	Cancer research 2004, 64: 6883
Currently, patients with neuroblastoma are classified into risk groups (e.g., according to the Children's Oncology Group risk-stratification) to guide physicians in the choice of the most appropriate therapy. Despite this careful stratification, the survival rate for patients with high-risk neuroblastoma remains <30%, and it is not possible to predict which of these high-risk patients will survive or succumb to the disease. Therefore, we have performed gene expression profiling using cDNA microarrays containing 42,578 clones and used artificial neural networks to develop an accurate predictor of survival for each individual patient with neuroblastoma. Using principal component analysis we found that neuroblastoma tumors exhibited inherent prognostic specific gene expression profiles. Subsequent artificial neural network-based prognosis prediction using expression levels of all 37,920 good-quality clones achieved 88% accuracy. Moreover, using an artificial neural network-based gene minimization strategy in a separate analysis we identified 19 genes, including 2 prognostic markers reported previously, MYCN and CD44, which correctly predicted outcome for 98% of these patients. In addition, these 19 predictor genes were able to additionally partition Children's Oncology Group-stratified high-risk patients into two subgroups according to their survival status (P = 0.0005). Our findings provide evidence of a gene expression signature that can predict prognosis independent of currently known risk factors and could assist physicians in the individual management of patients with high-risk neuroblastoma.
Weihkopf T, Blettner M, Dantonello T, Jung I, Klingebiel T, Koscielniak E, Lückel M, Spix C, Kaatsch P	Incidence and time trends of soft tissue sarcomas in German children 1985-2004 - a report from the population-based German Childhood Cancer Registry.	European journal of cancer 2008, 44: 432
The incidence of soft tissue sarcoma (STS) in Europe is increasing, but it is unclear whether this increase can also be seen in Germany. We analysed the heterogeneous group of STS recorded to the German Childhood Cancer Registry (GCCR) between 1985 and 2004 with respect to incidence data. Age-specific, age-standardised and cumulative incidence rates were calculated. Additionally, the average annual percent change (AAPC), derived from a Poisson regression model, was estimated, using time in years as the explanatory, continuous variable. Two thousand sixty-one children were diagnosed at a median age of 72 months. Most common are rhabdomyosarcomas (RMS) (n=1202) and fibrosarcomas (n=174). The age-standardised incidence rate (ASR) is 0.9 per 100,000/year for all STS, 0.70 for rhabdomyosarcoma-like (n=1588) and 0.18 for non-rhabdomyosarcoma-like (n=411) STS. AAPC is +0.4% (95%-confidence interval [-0.4;+1.2%]) for STS. In Germany, the increase in incidence rate is less evident than in other European countries.
Weimar, C et al.tri	Zerebrale Sinus - und Venenthrombose.	Leitlinien für Diagnostik und Therapie in der Neurologie (Hrsg.: Diener HC, Weimar C) 2012
Weiss JBW, Wagner AE, Eberherr C, Häberle B, Vokuhl C, von Schweinitz D, Kappler R	High expression of IGF2-derived intronic miR-483 predicts outcome in hepatoblastoma.	Cancer biomarkers 2020, 28: 321
The role of microRNAs (miRs) as biomarkers to predict outcome in hepatoblastoma (HB), the most common malignant liver tumor in childhood, has still to be determined. Recently, the so-called four-miR signature has been described to efficiently stratify HB patients according to their prognosis.
Weißert K, Ammann S, Kögl T, Dettmer-Monaco V, Schell C, Cathomen T, Ehl S, Aichele P	Adoptive T cell therapy cures mice from active hemophagocytic lymphohistiocytosis (HLH).	EMBO molecular medicine 2022, 14:e16085
Primary hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome caused by impaired lymphocyte cytotoxicity. First-line therapeutic regimens directed against activated immune cells or secreted cytokines show limited efficacy since they do not target the underlying immunological problem: defective lymphocyte cytotoxicity causing prolonged immune stimulation. A potential rescue strategy would be the adoptive transfer of ex vivo gene-corrected autologous T cells. However, transfusion of cytotoxicity-competent T cells under conditions of hyperinflammation may cause more harm than benefit. As a proof-of-concept for adoptive T cell therapy (ATCT) under hyperinflammatory conditions, we transferred syngeneic, cytotoxicity-competent T cells into mice with virally triggered active primary HLH. ATCT with functional syngeneic trigger-specific T cells cured Jinx mice from active HLH without life-threatening side effects and protected Perforin-deficient mice from lethal HLH progression by reconstituting cytotoxicity. Cured mice were protected long-term from HLH relapses. A threshold frequency of transferred T cells with functional differentiation was identified as a predictive biomarker for long-term survival. This study is the first proof-of-concept for ATCT in active HLH.
Weimar C, Beyer-Westendorf J, Bohmann FO, Hahn G, Halimeh S, Holzhauer S, Kalka C, Knoflach M, Koennecke HC, Masuhr F, Mono ML, Nowak-Göttl U, Scherret E, Schlamann M, Linnemann B	New recommendations on cerebral venous and dural sinus thrombosis from the German consensus-based (S2k) guideline.	Neurological research and practice 2024, 6: 23
Over the last years, new evidence has accumulated on multiple aspects of diagnosis and management of cerebral venous and dural sinus thrombosis (CVT) including identification of new risk factors, studies on interventional treatment as well as treatment with direct oral anticoagulants. Based on the GRADE questions of the European Stroke Organization guideline on this topic, the new German guideline on CVT is a consensus between expert representatives of Austria, Germany and Switzerland. New recommendations include:• CVT occurring in the first weeks after SARS-CoV-2 vaccination with vector vaccines may be associated with severe thrombocytopenia, indicating the presence of a prothrombotic immunogenic cause (Vaccine-induced immune thrombotic thrombocytopenia; VITT).• D-dimer testing to rule out CVT cannot be recommended and should therefore not be routinely performed.• Thrombophilia screening is not generally recommended in patients with CVT. It should be considered in young patients, in spontaneous CVT, in recurrent thrombosis and/or in case of a positive family history of venous thromboembolism, and if a change in therapy results from a positive finding.• Patients with CVT should preferably be treated with low molecular weight heparine (LMWH) instead of unfractionated heparine in the acute phase.• On an individual basis, endovascular recanalization in a neurointerventional center may be considered for patients who deteriorate under adequate anticoagulation.• Despite the overall low level of evidence, surgical decompression should be performed in patients with CVT, parenchymal lesions (congestive edema and/or hemorrhage) and impending incarceration to prevent death.• Following the acute phase, oral anticoagulation with direct oral anticoagulants instead of vitamin K antagonists should be given for 3 to 12 months to enhance recanalization and prevent recurrent CVT as well as extracerebral venous thrombosis.• Women with previous CVT in connection with the use of combined hormonal contraceptives or pregnancy shall refrain from continuing or restarting contraception with oestrogen-progestagen combinations due to an increased risk of recurrence if anticoagulation is no longer used.• Women with previous CVT and without contraindications should receive LMWH prophylaxis during pregnancy and for at least 6 weeks post partum.Although the level of evidence supporting these recommendations is mostly low, evidence from deep venous thrombosis as well as current clinical experience can justify the new recommendations.This article is an abridged translation of the German guideline, which is available online.
Welte K, Reiter A, Mempel K, Pfetsch M, Schwab G, Schrappe M, Riehm H	A randomized phase-III study of the efficacy of granulocyte colony-stimulating factor in children with high-risk acute lymphoblastic leukemia. Berlin-Frankfurt-Münster Study Group.	Blood 1996, 87: 3143
Wellmann S Guschmann	Activation of the HIF pathway in childhood ALL, prognostic implications of VEGF.	Leukemia 2004
Wellmann S, Moderegger E, Zelmer A, Bettkober M, von Stackelberg A, Henze G, Seeger K	FLT3 mutations in childhood acute lymphoblastic leukemia at first relapse.	Leukemia 2005, 19: 467
Welte K, Zeidler C, Dale DC	Severe congenital neutropenia.	Seminars in hematology 2006, 43: 189
Severe congenital neutropenia (CN) includes a variety of hematologic disorders characterized by severe neutropenia, with absolute neutrophil counts (ANC) below 0.5 x 10(9)/L, and associated with severe systemic bacterial infections from early infancy. One subtype of CN, Kostmann syndrome, is an autosomal recessive disorder, characterized histopathologically by early-stage maturation arrest of myeloid differentiation. CN with similar clinical features occurs as an autosomal dominant disorder and many sporadic cases also have been reported. This genetic heterogeneity suggests that several pathophysiological mechanisms may lead to this common clinical phenotype. Recent studies on the genetic bases of CN have detected inherited or spontaneous point mutations in the neutrophil elastase gene (ELA 2) in about 60% to 80% of patients and, less commonly, mutations in other genes. Acquisition of additional genetic defects during the course of the disease, for example, granulocyte colony-stimulating factor (G-CSF) receptor gene mutations and cytogenetic aberrations, indicates an underlying genetic instability as a common feature for all congenital neutropenia subtypes. Data on more than 600 patients with CN collected by the Severe Chronic Neutropenia International Registry (SCNIR) demonstrate that, regardless of the particular CN subtype, more than 95% of these patients respond to recombinant human (rHu)G-CSF with ANCs that can be maintained above 1.0 x 10(9)/L. Adverse events include mild splenomegaly, osteoporosis, and malignant transformation into myelodysplasia (MDS)/leukemia. If and how G-CSF treatment impacts on these adverse events is not fully understood. In recent analyses the influence of the G-CSF dose required to achieve neutrophil response (ANC >1,000/microL) in the risk of developing acute myeloid leukemia (AML) has been reported. Hematopoietic stem cell transplantation (HSCT) is still the only treatment available for patients who are refractory to G-CSF treatment.
Wells EM, Walsh KS, Khademian ZP, Keating RF, Packer RJ	The cerebellar mutism syndrome and its relation to cerebellar cognitive function and the cerebellar cognitive affective disorder.	Developmental disabilities research reviews 2008, 14: 221
The postoperative cerebellar mutism syndrome (CMS), consisting of diminished speech output, hypotonia, ataxia, and emotional lability, occurs after surgery in up to 25% of patients with medulloblastoma and occasionally after removal of other posterior fossa tumors. Although the mutism is transient, speech rarely normalizes and the syndrome is associated with long-term adverse neurological, cognitive, and psychological sequelae. The clinical, neuroradiographic, and neuropsychological findings associated with CMS as well as possible mechanisms of injury are reviewed. Theories about the pathophysiology of CMS have evolved along with our understanding of the cerebellum as an important structure in the distributive neurocircuitry underlying complex speech, cognition, and behavior. CMS shares many similarities with the cerebellar cognitive affective syndrome, more commonly described in adults and consisting of disturbances of executive function, visuospatial skills, nonmotor language, and affect regulation. Future directions include more thorough neuropsychological characterization, functional and diffusion tensor imaging studies, and investigations into the underlying differences that may make some patients more vulnerable to CMS.
Welter N, Wagner A, Furtwängler R, Melchior P, Kager L, Vokuhl C, Schenk JP, Meier CM, Siemer S, Gessler M, Graf N	Characteristics of Nephroblastoma/Nephroblastomatosis in Children with a Clinically Reported Underlying Malformation or Cancer Predisposition Syndrome.	Cancers 2021, 13
(1) Background: about 10% of Wilms Tumor (WT) patients have a malformation or cancer predisposition syndrome (CPS) with causative germline genetic or epigenetic variants. Knowledge on CPS is essential for genetic counselling. (2) Methods: this retrospective analysis focused on 2927 consecutive patients with WTs registered between 1989 and 2017 in the SIOP/GPOH studies. (3) Results: Genitourinary malformations (GU, = 66, 2.3%), Beckwith-Wiedemann spectrum (BWS, = 32, 1.1%), isolated hemihypertrophy (IHH, = 29, 1.0%), Denys-Drash syndrome (DDS, = 24, 0.8%) and WAGR syndrome ( = 20, 0.7%) were reported most frequently. Compared to others, these patients were younger at WT diagnosis (median age 24.5 months vs. 39.0 months), had smaller tumors (349.4 mL vs. 487.5 mL), less often metastasis (8.2% vs. 18%), but more often nephroblastomatosis (12.9% vs. 1.9%). WT with IHH was associated with blastemal WT and DDS with stromal subtype. Bilateral WTs were common in WAGR (30%), DDS (29%) and BWS (31%). Chemotherapy induced reduction in tumor volume was poor in DDS (0.4% increase) and favorable in BWS (86.9% reduction). The event-free survival (EFS) of patients with BWS was significantly ( = 0.002) worse than in others. (4) Conclusions: CPS should be considered in WTs with specific clinical features resulting in referral to a geneticist. Their outcome was not always favorable.
Welter N, Wagner A, Furtwängler R, Melchior P, Kager L, Vokuhl C, Schenk JP, Meier CM, Siemer S, Gessler M, Graf N	Correction: Welter et al. Characteristics of Nephroblastoma/Nephroblastomatosis in Children with a Clinically Reported Underlying Malformation or Cancer Predisposition Syndrome. Cancers 2021, 13, 5016.	Cancers 2021, 13
In the original article [...].
Welter N, Furtwängler R, Schneider G, Graf N, Schenk JP	[Tumor predisposition syndromes and nephroblastoma : Early diagnosis with imaging].	Radiologie 2022, 62: 1033
The Beckwith-Wiedemann spectrum (BWSp) as well as the WT1-related syndromes, Denys-Drash syndrome (DDS) and WAGR spectrum (Wilms tumor, Aniridia, genitourinary anomalies and a range of developmental delays) are tumor predisposition syndromes (TPS) of Wilms tumor (WT). Patients with associated TPS are at higher risk of developing chronic kidney disease and bilateral and metachronous tumors as well as nephrogenic rests.
Wenninger K, Helmes A, Bengel J, Lauten M, Völkel S, Niemeyer CM	Coping in long-term survivors of childhood cancer: relations to psychological distress.	Psycho-oncology 2013, 22: 854
The goal of this study was to describe coping strategies and their associations with psychological distress in young adult survivors of childhood cancer.
Werner M, Fuchs N, Salzer-Kuntschik M, Winkler K, Delling G	Therapy-induced changes in osteosarcoma after neoadjuvant chemotherapy (COSS 86 Therapy Study). Correlation between morphologic findings and clinical follow-up.	Pathologe 1996, 17: 35
Werner M, Heintz A, Delling G	DNA cytometry of solitary and aneurysmal bone cysts and low malignancy and high malignancy central osteosarcomas. Current significance within the scope of morphologic diagnosis of intraosseous cystic and osteoblastic lesions.	Pathologe 1996, 17: 44
Wermes C, Rietze M, Sykora KW, Ganser A	Integrationsprojekt als Weg in die Zukunft Erfolgreicher Einstieg in das Berufsleben für Jugendliche mit Hämophilie.	Hämostaseologie, Supplement 2010, 30 1: 60-61
Westermeier T, Michaelis J	Applicability of the Poisson distribution to model the data of the German Children's Cancer Registry.	Radiat Environ Biophys 1995, 34: 7
Wessalowski R, Blohm M, Calaminus G, Engert J, Harms D, Krause I, Kruck H, Grüttner HP, Pape H, Göbel U	Treatment results in children and adolescents with loco-regional recurrences of abdominal germ cell tumors (GCTs): a pilot-study with PEI chemotherapy and regional deep hyperthermia (RHT) in comparison to a matched cohort.	Klinische Padiatrie 1997, 209: 250
In this study treatment results in children and adolescents (n = 32) suffering from loco-regional abdominal relapses of germ cell tumors (GCT) (7 embryonal carcinoma, 17 Yolk sac tumors, 8 immature teratomas) aged from 1;0 to 23;3 years (mean = 10;11 years) were evaluated. In this pilot study 9 patients were treated with cisplatinum (40 mg/m2 on days 1 and 4), etoposide (100 mg/m2 on days 1 to 4), and ifosfamide (2000 mg/m2 on days 1 to 4) (PEI) +/- radiation in combination with regional deep hyperthermia (RHI). In sedation RHT was induced by non-invasive heat applicators (Sigma-40 and Sigma 60, BSD Medical Corporation, Utah, USA). In 7 out of these 9 patients with recurrent GCT a tumor response (5 CR, 2 PR, 1 SD, 1 PD) was found. In addition, in 2 patients a complete tumor resection could be achieved inspite of 2 previous incomplete tumor resections each. Five out of 9 patients are living event-free after an observation period ranging from 8 to 40 months (median = 15 months). Treatment results of this RHT study population were compared with treatment results in patients with recurrent GCT, who received conventional relapse therapy (chemotherapy/ surgery +/- radiation) alone. In this matched cohort 5 out of 23 patients are living event-free after an observation time ranging from 1 to 120 months (median = 8 months). According to Kaplan-Maier life table analysis, patients with relapse therapy combined with RHT have an event-free survival (EFS) of 0.41 +/- 0.33 whereas the matched cohort without RHT have an EFS of 0.16 +/- 0.25. The difference in treatment results of both groups is significant (Wilcoxon/p = 0.03). From the data presented in this study we conclude that children with loco-regional recurrences of extracranial non-testicular GCT have an unfavorable prognosis, unless local tumor control can be achieved. The additional application of RHT in combination with conventional therapy (PEI chemotherapy +/- radiation) can improve local tumor control and EFS in GCT patients with loco-regional recurrences. Therefore, based upon these results in the future MAKEI trial RHT will be applied to GCT patients with poor response to neoadjuvant chemotherapy alone as first line treatment.
Wessalowski R, Kruck H, Pape H, Kahn T, Willers R, Göbel U	Hyperthermia for the treatment of patients with malignant germ cell tumors.	Cancer 1998, 82: 793
Westermeier T, Kaatsch P, Schoetzau A, Michaelis J	Multiple primary neoplasms in childhood.	Eur J Cancer 1998, 34: 687
Westermann F, Muth D, Benner A, Bauer T, Henrich KO, Oberthuer A, Brors B, Beissbarth T, Vandesompele J, Pattyn F, Hero B, König R, Fischer M, Schwab M	Distinct transcriptional MYCN/c-MYC activities are associated with spontaneous regression or malignant progression in neuroblastomas.	Genome biology 2008, 9:R150
BACKGROUND: Amplified MYCN oncogene resulting in deregulated MYCN transcriptional activity is observed in 20% of neuroblastomas and identifies a highly aggressive subtype. In MYCN single-copy neuroblastomas, elevated MYCN mRNA and protein levels are paradoxically associated with a more favorable clinical phenotype, including disseminated tumors that subsequently regress spontaneously (stage 4s-non-amplified). In this study, we asked whether distinct transcriptional MYCN or c-MYC activities are associated with specific neuroblastoma phenotypes. RESULTS: We defined a core set of direct MYCN/c-MYC target genes by applying gene expression profiling and chromatin immunoprecipitation (ChIP, ChIP-chip) in neuroblastoma cells that allow conditional regulation of MYCN and c-MYC. Their transcript levels were analyzed in 251 primary neuroblastomas. Compared to localized-non-amplified neuroblastomas, MYCN/c-MYC target gene expression gradually increases from stage 4s-non-amplified through stage 4-non-amplified to MYCN amplified tumors. This was associated with MYCN activation in stage 4s-non-amplified and predominantly c-MYC activation in stage 4-non-amplified tumors. A defined set of MYCN/c-MYC target genes was induced in stage 4-non-amplified but not in stage 4s-non-amplified neuroblastomas. In line with this, high expression of a subset of MYCN/c-MYC target genes identifies a patient subtype with poor overall survival independent of the established risk markers amplified MYCN, disease stage, and age at diagnosis. CONCLUSIONS: High MYCN/c-MYC target gene expression is a hallmark of malignant neuroblastoma progression, which is predominantly driven by c-MYC in stage 4-non-amplified tumors. In contrast, moderate MYCN function gain in stage 4s-non-amplified tumors induces only a restricted set of target genes that is still compatible with spontaneous regression.
Wessel T, Balcerek M, Reinmuth S, Hohmann C, Keil T, Henze G, Borgmann-Staudt A	Age at menarche in childhood cancer survivors: results of a nationwide survey in Germany.	Hormone research in paediatrics 2012, 77: 108
Background/Aims: With rising cure rates of childhood cancer, side effects of treatment are attracting increasing interest. The present analysis evaluates the influence of tumor localization, radiotherapy and chemotherapy on the age of menarche. Methods: 4,689 former pediatric oncology patients, diagnosed 1980-2004, were contacted in collaboration with the German Childhood Cancer Registry. Results: 1,036 out of 1,461 female participants reported their age at menarche and had an oncological diagnosis before menarche. The median age at menarche was 13 years, compared to 12.8 years in the German general population. A significant delay of menarche was seen in patients with pituitary radiation doses of ≥30 Gy (mean 13.6 years, SD 2.2) compared to <30 Gy (mean 12.5 years, SD 1.4, p = 0.05). Patients with additional spinal radiation were even older at menarche (mean 14.4 years, SD 2.5). Pelvic and pelvic-near radiation significantly delayed onset of menarche (mean 14.0 years, SD 1.9 and mean 14.3, SD 2.6, respectively, p < 0.001). Only some chemotherapeutic agents (carboplatin/cisplatin, etoposide) were associated with a menarcheal delay of <1 year. Conclusion: Overall, female childhood cancer survivors showed a normal menarcheal age. Pituitary radiation dosage of ≥30 Gy, spinal and pelvic radiotherapy were associated with a moderate delay in the occurrence of menarche.
Wessel T, Balcerek M, Reinmuth S, Hohmann C, Keil T, Henze G, Borgmann-Staudt A	Age at menarche in childhood cancer survivors: results of a nationwide survey in Germany.	Hormone research in paediatrics 2012, 77: 108
With rising cure rates of childhood cancer, side effects of treatment are attracting increasing interest. The present analysis evaluates the influence of tumor localization, radiotherapy and chemotherapy on the age of menarche.
Wessalowski R, Schneider DT, Mils O, Friemann V, Kyrillopoulou O, Schaper J, Matuschek C, Rothe K, Leuschner I, Willers R, Schönberger S, Göbel U, Calaminus G, MAKEI study group	Regional deep hyperthermia for salvage treatment of children and adolescents with refractory or recurrent non-testicular malignant germ-cell tumours: an open-label, non-randomised, single-institution, phase 2 study.	The lancet oncology 2013, 14: 843
Although the survival of children and adolescents with malignant germ-cell tumours has improved greatly in recent years, the outcome remains poor for those with refractory or recurrent malignant germ-cell tumours. We aimed to determine whether objective tumour response could be achieved in patients with refractory or recurrent malignant germ-cell tumours with PEI-regional deep hyperthermia as salvage treatment.
Weyand AC, Pipe SW	New therapies for hemophilia.	Blood 2019 Jan 31; 133: 389
Whelan J, McTiernan A, Weston C, Douglas C, Grimer R, Cassoni A, Paulussen M, Jürgens H, Craft A, Lewis, I	Consequences of different approaches to local treatment of Ewing's sarcoma within an international randomised controlled trial: Analysis of EICESS-92.	Journal of Clinical Oncology 2006, 24; 528S
Whelan KF, Stratton K, Kawashima T, Waterbor JW, Castleberry RP, Stovall M, Sklar CA, Packer RJ, Mitby P, Aitken CL, Blatt J, Robison LL, Mertens AC	Ocular late effects in childhood and adolescent cancer survivors: a report from the childhood cancer survivor study.	Pediatric blood & cancer 2010, 54: 103
Approximately 80% of children currently survive 5 years following diagnosis of their cancer. Studies based on limited data have implicated certain cancer therapies in the development of ocular sequelae in these survivors.
Whelan JS, Bielack SS, Marina N, Smeland S, Jovic G, Hook JM, Krailo M, Anninga J, Butterfass-Bahloul T, Böhling T, Calaminus G, Capra M, Deffenbaugh C, Dhooge C, Eriksson M, Flanagan AM, Gelderblom H, Goorin A, Gorlick R, Gosheger G, Grimer RJ, Hall KS, Helmke K, Hogendoorn PC, Jundt G, Kager L, Kuehne T, Lau CC, Letson GD, Meyer J, Meyers PA, Morris C, Mottl H, Nadel H, Nagarajan R, Randall RL, Schomberg P, Schwarz R, Teot LA, Sydes MR, Bernstein M, EURAMOS collaborators	EURAMOS-1, an international randomised study for osteosarcoma: results from pre-randomisation treatment.	Annals of oncology : official journal of the European Society for Medical Oncology / ESMO 2015, 26: 407
Four international study groups undertook a large study in resectable osteosarcoma, which included two randomised controlled trials, to determine the effect on survival of changing post-operative chemotherapy based on histological response.
Whelan J, Hackshaw A, McTiernan A, Grimer R, Spooner D, Bate J, Ranft A, Paulussen M, Jürgens H, Craft A, Lewis I	Survival is influenced by approaches to local treatment of Ewing sarcoma within an international randomised controlled trial: analysis of EICESS-92.	Clinical sarcoma research 2018, 8: 6
Two national clinical trial groups, United Kingdom Children's Cancer and Leukaemia Group (CCLG) and the German Paediatric Oncology and Haematology Group (GPOH) together undertook a randomised trial, EICESS-92, which addressed chemotherapy options for Ewing's sarcoma. We sought the causes of unexpected survival differences between the study groups.
Whelan J, Le Deley MC, Dirksen U, Le Teuff G, Brennan B, Gaspar N, Hawkins DS, Amler S, Bauer S, Bielack S, Blay JY, Burdach S, Castex MP, Dilloo D, Eggert A, Gelderblom H, Gentet JC, Hartmann W, Hassenpflug WA, Hjorth L, Jimenez M, Klingebiel T, Kontny U, Kruseova J, Ladenstein R, Laurence V, Lervat C, Marec-Berard P, Marreaud S, Michon J, Morland B, Paulussen M, Ranft A, Reichardt P, van den Berg H, Wheatley K, Judson I, Lewis I, Craft A, Jürgens H, Oberlin O, Euro-EWING99 and EWING-2008 Investigators	High-Dose Chemotherapy and Blood Autologous Stem-Cell Rescue Compared With Standard Chemotherapy in Localized High-Risk Ewing Sarcoma: Results of Euro-E. W.I. N.G. 99 and Ewing-2008.	J Clin Oncol 2018
Purpose For over 30 years, the place of consolidation high-dose chemotherapy in Ewing sarcoma (ES) has been controversial. A randomized study was conducted to determine whether consolidation high-dose chemotherapy improved survival in patients with localized ES at high risk for relapse. Methods Randomization between busulfan and melphalan (BuMel) or standard chemotherapy (vincristine, dactinomycin, and ifosfamide [VAI], seven courses) was offered to patients if they were younger than 50 years of age with poor histologic response (≥ 10% viable cells) after receiving vincristine, ifosfamide, doxorubicin, and etoposide (six courses); or had a tumor volume at diagnosis ≥ 200 mL if unresected, or initially resected, or resected after radiotherapy. A 15% improvement in 3-year event-free survival (EFS) was sought (hazard ratio [HR], 0.60). Results Between 2000 and 2015, 240 patients classified as high risk (median age, 17.1 years) were randomly assigned to VAI (n = 118) or BuMel (n = 122). Seventy-eight percent entered the trial because of poor histologic response after chemotherapy alone. Median follow-up was 7.8 years. In an intent-to-treat analysis, the risk of event was significantly decreased by BuMel compared with VAI: HR, 0.64 (95% CI, 0.43 to 0.95; P = .026); 3- and 8-year EFS were, respectively, 69.0% (95% CI, 60.2% to 76.6%) versus 56.7% (95% CI, 47.6% to 65.4%) and 60.7% (95% CI, 51.1% to 69.6%) versus 47.1% (95% CI, 37.7% to 56.8%). Overall survival (OS) also favored BuMel: HR, 0.63 (95% CI, 0.41 to 0.95; P = .028); 3- and 8-year OS were, respectively, 78.0% (95% CI, 69.6% to 84.5%) versus 72.2% (95% CI, 63.3% to 79.6%) and 64.5% (95% CI, 54.4% to 73.5%) versus 55.6% (95% CI, 45.8% to 65.1%). Results were consistent in the sensitivity analysis. Two patients died as a result of BuMel-related toxicity, one after standard chemotherapy. Significantly more BuMel patients experienced severe acute toxicities from this course of chemotherapy compared with multiple VAI courses. Conclusion BuMel improved EFS and OS when given after vincristine, ifosfamide, doxorubicin, and etoposide induction in localized ES with predefined high-risk factors. For this group of patients, BuMel may be an important addition to the standard of care.
White GC 2nd, Rosendaal F, Aledort LM, Lusher JM, Rothschild C, Ingerslev J, Factor VIII and Factor IX Subcommittee	Definitions in hemophilia. Recommendation of the scientific subcommittee on factor VIII and factor IX of the scientific and standardization committee of the International Society on Thrombosis and Haemostasis.	Thromb Haemost 2001, 85: 560
Whitehead VM	Acquired and inherited disorders of cobalamin and folate in children.	British journal of haematology 2006, 134: 125
Whittle S, Venkatramani R, Schönstein A, Pack SD, Alaggio R, Vokuhl C, Rudzinski ER, Wulf AL, Zin A, Gruver JR, Arnold MA, Merks JHM, Hettmer S, Koscielniak E, Barr FG, Hawkins DS, Bisogno G, Sparber-Sauer M	Congenital spindle cell rhabdomyosarcoma: An international cooperative analysis.	European journal of cancer 2022, 168: 56
Spindle cell rhabdomyosarcoma (RMS) is a rare variant of RMS accounting for up to 10% of cases in infants. In older children and adults, spindle cell RMS is associated with MYOD1 mutations and a poor prognosis. In infants, it is associated with recurring fusions involving NCOA2 and VGLL2. Reports in the literature suggest a favorable prognosis for this subset, however, little is known about treatment and outcome data of infants with spindle cell RMS.
World Health Organization Classification of Tumours	Pathology and genetics: tumours of haematopoietic and lymphoid tussues.	IARC Press, Lyon 2001
World Health Organisation	Iron deficiency anemia. Assessment, prevention and control.	2001
WHO Press	International Classification of Functioning, Disability and Health: Children and Youth Version. Geneva.	WHO Press 2007, ISBN 978 92 4 154732 1
World Health Organisation	Worldwide prevalence of anaemia 1993–2005.	2008
World Health Organization	2008-2013 Action plan for the global strategy for the prevention and control of noncommunicable diseases.	WHO 2009
World Health Organization	Nutritional anaemias: tools for effective prevention and control.	World Health Organization Geneva 2017
WHO Classification of Tumours Editorial Board	Soft Tissue and Bone Tumours.	5th ed. Lyon: IARC Press 2020
Wick M, Pinggera W, Lehman P	Eisenstoffwechsel: Diagnostik und Therapie der Anämien.	Springer-Verlag Wien 1996, 3. Aufl.
Wickramasinghe SN	Congenital dyserythropoietic anaemias: clinical features, haematological morphology and new biochemical data.	Blood reviews 1998, 12: 178
Three types of congenital dyserythropoietic anaemia (CDA) were originally identified on the basis of the pattern of dysplastic changes in the erythroblasts and the results of the acidified serum lysis test (Ham test). These were designated CDA types I, II and III. Several other types have been described subsequently and new forms continue to be reported. Some patients with CDA develop iron overload even without repeated blood transfusion and may present with the complications of severe iron overload. Dysmorphic features are seen in some cases, especially of CDA type I. In CDA type II, incomplete processing of N-linked oligosaccharides leads to a marked reduction of polylactosamines associated with band 3 of the red cell membrane. A few cases of CDA type III develop lymphoid neoplasms. Some of the Swedish cases of CDA type III have developed a retinal abnormality characterized by angioid streaks and macular degeneration. The chromosomal localizations of the disease gene in CDA types I and II and in the Swedish family with CDA type III are now known, but the identities of the mutant genes are still unknown. Cases of CDA type I have shown a partial haematological response to interferon-alpha, however the biochemical basis of this response is unclear. An important step in the diagnosis of sporadic cases of CDA is the exclusion of known causes of acquired dyserythropoiesis.
Wickmann L, Lüders H, Dörffel W	18-FDG-PET-Befunde bei Kindern und Jugendlichen mit Morbus Hodgkin.	Klin Pädiatr 2003, 215: 146
Widemann BC, Balis FM, Murphy RF, Sorensen JM, Montello MJ, O'Brien M, Adamson PC	Carboxypeptidase-G2, thymidine, and leucovorin rescue in cancer patients with methotrexate-induced renal dysfunction.	J Clin Oncol 1997, 15: 2125
Methotrexate nephrotoxicity can lead to delayed methotrexate elimination and the development of life-threatening toxicity, which may not be preventable with the standard rescue agent leucovorin. In preclinical studies, we previously demonstrated that carboxypetidase-G2 (CPDG2) rapidly hydrolyzes methotrexate to nontoxic metabolites. A protocol for the compassionate use of CPDG2 in patients who develop nephrotoxicity while receiving high-dose methotrexate was therefore developed. The pharmacologic and clinical outcome of CPDG2 rescue administered with thymidine and leucovorin in 20 patients is presented here.
Widemann B, Balis F, Kempf-Bielack B, Bielack S, Pratt C, Ferrari S, Bacci G, Craft A, Adamson P	High-dose methotrexate-induced nephrotoxicity in patients with osteosarcoma.	Cancer 2004, 100: 2222
Widemann BC, Balis FM, Shalabi A, Boron M, O'Brien M, Cole DE, Jayaprakash N, Ivy P, Castle V, Muraszko K, Moertel CL, Trueworthy R, Hermann RC, Moussa A, Hinton S, Reaman G, Poplack D, Adamson PC	Treatment of accidental intrathecal methotrexate overdose with intrathecal carboxypeptidase G2.	J Natl Cancer Inst 2004, 96: 1557
The bacterial enzyme carboxypeptidase G2 (CPDG2) rapidly hydrolyzes methotrexate to inactive metabolites. We administered recombinant CPDG2 (2000 U) intrathecally to seven cancer patients 3 to 9 hours after they had received an accidental overdose of intrathecal methotrexate (median dose = 364 mg; range = 155-600 mg). Four of the seven patients had cerebrospinal fluid (CSF) exchange to remove methotrexate before CPDG2 administration. Immediate symptoms of the methotrexate overdoses included seizures (n = 5), coma (n = 2), and cardiopulmonary compromise (n = 2). Before CPDG2 administration, the median concentrations of methotrexate in CSF were 264 microM (range = 97-510 microM) among patients who had CSF exchange and 8050 microM (range = 2439-16 500 microM) among patients who did not. After intrathecal CPDG2 administration, methotrexate concentrations in CSF declined by more than 98%. All patients recovered completely from the intrathecal methotrexate overdose except for two patients who had memory impairments. Antibodies to CPDG2 were not detected in plasma after treatment with intrathecal CPDG2. Intrathecal CPDG2 is well tolerated, rapidly decreases CSF methotrexate concentrations, and appears to be efficacious for treating accidental intrathecal methotrexate overdoses.
Widemann BC, Balis FM, Kim A, Boron M, Jayaprakash N, Shalabi A, O'Brien M, Eby M, Cole DE, Murphy RF, Fox E, Ivy P, Adamson PC	Glucarpidase, leucovorin, and thymidine for high-dose methotrexate-induced renal dysfunction: clinical and pharmacologic factors affecting outcome.	J Clin Oncol 2010, 28: 3979
To assess the role of the recombinant bacterial enzyme, glucarpidase (carboxypeptidase-G(2)), leucovorin, and thymidine in the management and outcome of patients with high-dose methotrexate (HDMTX) -induced nephrotoxicity.
Wieland R, Havers W	Retinoblastome. In: Gadner H, Gaedicke G, Niemeyer CH, Ritter J (Hrsg.): Pädiatrische Hämatologie und Onkologie.	Springer-Verlag 2006, 823
Wieland R, Havers W	Retinoblastome, in: Gadner H, Gaedicke G, Niemeyer CH, Ritter J: Pädiatrische Hämatologie und Onkologie.	Springer Medizin Verlag 2006, 823
Wiener L, Kazak AE, Noll RB, Patenaude AF, Kupst MJ	Standards for the Psychosocial Care of Children With Cancer and Their Families: An Introduction to the Special Issue.	Pediatric blood & cancer 2015, 62 Suppl 5:S419
Pediatric oncology psychosocial professionals collaborated with an interdisciplinary group of experts and stakeholders and developed evidence-based standards for pediatric psychosocial care. Given the breadth of research evidence and traditions of clinical care, 15 standards were derived. Each standard is based on a systematic review of relevant literature and used the AGREE II process to evaluate the quality of the evidence. This article describes the methods used to develop the standards and introduces the 15 articles included in this special issue. Established standards help ensure that all children with cancer and their families receive essential psychosocial care.
Wiese M, Walther N, Diederichs C, Schill F, Monecke S, Salinas G, Sturm D, Pfister SM, Dressel R, Johnsen SA, Kramm CM	The ß-catenin/CBP-antagonist ICG-001 inhibits pediatric glioma tumorigenicity in a Wnt-independent manner.	Oncotarget 2017 Apr 18; 8: 27300
Wiederer L, Bertsch A, Eber S	Seltene Anämien im Kindesalter.	Päd Prax 2020, 94: 85
Anämien im Kindes- und Jugendalter stellen laut Robert-Koch-Institut sowohl im ambulanten Alltag als auch in der klinischen Versorgung ein häufig gesehenes Krankheitsbild mit einer Prävalenz von 7% im Alter unter 17 Jahren dar. Die häufigsten Ursachen sind erworbene alimentäre Mängel an Eisen und Vitamin B12 sowie Blutverlust in der Menarche. Im Folgenden werden angeborene Formen der Anämie erläutert, die nur einen Bruchteil der Prävalenz ausmachen, im Verlauf aber fulminant verlaufen können und daher immer als Differenzialdiagnose in Betracht gezogen werden sollten. Um eine bestmögliche Versorgung zu gewährleisten, müssen kritische Situationen und Krankheitsexazerbation erkannt werden, um eine schnellstmögliche Therapie einzuleiten.
Willig TN, Niemeyer CM, Leblanc T, Tiemann C, Robert A, Budde J, Lambiliotte A, Kohne E, Souillet G, Eber S, Stephan JL, Girot R, Bordigoni P, Cornu G, Blanche S, Guillard JM, Mohandas N, Tchernia G	Identification of new prognosis factors from the clinical and epidemiologic analysis of a registry of 229 Diamond-Blackfan anemia patients. DBA group of Société d'Hématologie et d'Immunologie Pédiatrique (SHIP), Gesellshaft für Pädiatrische Onkologie und Hämatologie (GPOH), and the European Society for Pediatric Hematology and Immunology (ESPHI).	Pediatric research 1999, 46: 553
Diamond-Blackfan anemia (DBA) is a constitutional disease characterized by a specific maturation defect in cells of erythroid lineage. We have assembled a registry of 229 DBA patients, which includes 151 patients from France, 70 from Germany, and eight from other countries. Presence of malformations was significantly and independently associated with familial history of DBA, short stature at presentation (before any steroid therapy), and absence of hypotrophy at birth. Two hundred twenty-two patients were available for long-term follow-up analysis (median, 111.5 mo). Of these individuals, 62.6% initially responded to steroid therapy. Initial steroid responsiveness was found significantly and independently associated with older age at presentation, familial history of DBA, and a normal platelet count at the time of diagnosis. Severe evolution of the disease (transfusion dependence or death) was significantly and independently associated with a younger age at presentation and with a history of premature birth. In contrast, patients with a familial history of the disease experienced a better outcome. Outcome analysis revealed the benefit of reassessing steroid responsiveness during the course of the disease for initially nonresponsive patients. Bone marrow transplantation was successful in 11/13 cases; HLA typing of probands and siblings should be performed early if patients are transfusion dependent, and cord blood should be preserved. Incidence of DBA (assessed for France over a 13-y period) is 7.3 cases per million live births without effect of seasonality on incidence of the disease or on malformative status. Similarly, no parental imprinting effect or anticipation phenomenon could be documented in families with dominant inheritance.
Willemse M, Seriu T, Hettinger K, D'Aniello E, Hop W, Panzer-Grumayer E, Biondi A, Schrappe M, Kamps W, Masera G, Gadner H, Riehm H, Bartram C, van Dongen J	Detection of minimal residual disease identifies differences in treatment response between T-ALL and precursor B-ALL.	Blood 2002, 99: 4386
Wilda M, Bruch J, Harder L, Rawer D, Reiter A, Borkhardt A, Woessmann W	Inactivation of the ARF-MDM-2-p53 pathway in sporadic Burkitt's lymphoma in children.	Leukemia 2004, 18: 584
Willich N, Ernst I, Pape H, Rübe C, Timmermann B, Asadpour B, Kortmann RD, Bölling T	Evaluation of side effects after radiotherapy in childhood and adolescence: from retrospective case reports to a prospective, multicentric and transnational approach.	Strahlentherapie und Onkologie 2009, 185 Suppl 2: 3
Willer A, Gerss J, König T, Franke D, Kühnel HJ, Henze G, von Stackelberg A, Möricke A, Schrappe M, Boos J, Lanvers-Kaminsky C	Anti-Escherichia coli asparaginase antibody levels determine the activity of second-line treatment with pegylated E coli asparaginase: a retrospective analysis within the ALL-BFM trials.	Blood 2011, 118: 5774
Hypersensitivity reactions limit the use of the antileukemic enzyme asparaginase (ASE). We evaluated Ab levels against Escherichia coli ASE and ASE activity in 1221 serum samples from 329 patients with acute lymphoblastic leukemia who had received ASE treatment according to the ALL-BFM 2000 or the ALL-REZ BFM 2002 protocol for primary or relapsed disease. ASE activity during first-line treatment with native E coli ASE and second-line treatment with pegylated E coli ASE was inversely related to anti-E coli ASE Ab levels (P < .0001; Spearman rank order correlation). An effect on ASE activity during second-line treatment with pegylated E coli ASE was, however, only observed when anti-E coli ASE Ab levels were high (> 200 AU/mL). In the presence of moderate or intermediate Ab levels (6.25-200 AU/mL) the switch from native to pegylated E coli ASE resulted in a significant increase of ASE activity above the threshold of 100 U/L (P < .05). Erwinia chrysanthemi ASE activity was not correlated with anti-E coli ASE Ab levels. Erwinia ASE was found to be the best ASE alternative if Ab levels against E coli ASE exceed 200 AU/mL. This retrospective analysis is the first to describe the relationship between the level of anti-E coli ASE Abs and serum activity of pegylated E coli ASE used second-line after native E coli ASE.
Wilne S, Collier J, Kennedy C, Jenkins A, Grout J, Mackie S, Koller K, Grundy R, Walker D	Progression from first symptom to diagnosis in childhood brain tumours.	European journal of pediatrics 2012, 171: 87
This study was undertaken to investigate the evolution of clinical features between onset of symptoms and diagnosis in children with brain tumours and to identify ways of shortening the time to diagnosis. One hundred and thirty-nine children with a brain tumour were recruited from four UK paediatric neuro-oncology centres. Children had a median of one symptom or sign at symptom onset and six by diagnosis. The symptoms and/or signs experienced at symptom onset and at diagnosis were as follows: headache in 55 and 81 children, nausea and vomiting in 39 and 88 children, motor system abnormalities in 31 and 93 children, cranial nerve palsies in 24 and 75 children, visual system abnormalities in 23 and 96 children, endocrine or growth abnormalities in 10 and 35 children and behavioural change in 4 and 55 children. The median time between symptom onset and diagnosis (symptom interval) was 3.3 months. A longer symptom interval was associated with head tilt, cranial nerve palsies, endocrine and growth abnormalities and reduced visual acuity. More than half of children with brain tumours developed problems with vision and more than a third developed motor problems, cranial nerve palsies, behavioural change, or nausea and vomiting between symptom onset and diagnosis.
Wilhelm M, Dirksen U, Bielack SS, Whelan JS, Lewis IJ, Jürgens H, Ferrari S, Sundby Hall K, Cleton-Jansen AM, Stark D	ENCCA WP17-WP7 consensus paper on teenagers and young adults (TYA) with bone sarcomas.	Annals of oncology 2014, 25: 1500
Teenagers and young adults (TYA) cancer contributes substantially to morbidity and mortality in a population with much to offer society. TYA place distinct challenges upon cancer care services, many reporting feeling marginalized and their needs not being met in adult or paediatric cancer services. Bone tumours such as osteosarcoma and Ewing sarcoma, because of their age at presentation and the complexity of their care, are where challenges in managing (TYA) with cancer have often been most readily apparent. Bone sarcomas may be managed by paediatric or medical oncologists, and require fastidious attention to protocol. A lack of recent improvement in survival in TYA with bone tumours may be linked to a lack of specialist care, poor concordance with therapy in some situations and TYA-specific pharmacology. Participation in clinical trials, particularly of young adults, is low, hindering progress. All these requirements may be best met by a concerted effort to create collaborative care between adult and paediatric experts in bone sarcoma, working together to meet TYA patients' needs.
Willasch AM, Peters C, SedlÃ¡Äek P, Dalle JH, Kitra-Roussou V, Yesilipek A, Wachowiak J, Lankester A, Prete A, Hamidieh AA, Ifversen M, Buechner J, KrivÃ¡n G, Hamladji RM, Diaz-de-Heredia C, Skorobogatova E, Michel G, Locatelli F, Bertaina A, Veys P, Dupont S, Or R, GÃ¼ngÃ¶r T, Aleinikova O, Sufliarska S, Sundin M, Rascon J, Kaare A, Nemet D, Fagioli F, Klingebiel TE, Styczynski J, Bierings M, Nagy K, Abecasis M, Afanasyev B, Ansari M, Vettenranta K, Alseraihy A, Chybicka A, Robinson S, Bertrand Y, Kupesiz A, Ghavamzadeh A, Campos A, Pichler H, Dalissier A, Labopin M, Corbacioglu S, Balduzzi A, Galimard JE, Bader P, EBMT Paediatric Diseases Working Party	Myeloablative conditioning for allo-HSCT in pediatric ALL: FTBI or chemotherapy?-A multicenter EBMT-PDWP study.	Bone marrow transplantation 2020, Epup ahead of print
Although most children with acute lymphoblastic leukemia (ALL) receive fractionated total body irradiation (FTBI) as myeloablative conditioning (MAC) for allogeneic hematopoietic stem cell transplantation (allo-HSCT), it is an important matter of debate if chemotherapy can effectively replace FTBI. To compare outcomes after FTBI versus chemotherapy-based conditioning (CC), we performed a retrospective EBMT registry study. Children aged 2-18 years after MAC for first allo-HSCT of bone marrow (BM) or peripheral blood stem cells (PBSC) from matched-related (MRD) or unrelated donors (UD) in first (CR1) or second remission (CR2) between 2000 and 2012 were included. Propensity score weighting was used to control pretreatment imbalances of the observed variables. 3.054 patients were analyzed. CR1 (1.498): median follow-up (FU) after FTBI (1.285) and CC (213) was 6.8 and 6.1 years. Survivals were not significantly different. CR2 (1.556): median FU after FTBI (1.345) and CC (211) was 6.2 years. Outcomes after FTBI were superior as compared with CC with regard to overall survival (OS), leukemia-free survival (LFS), relapse incidence (RI), and nonrelapse mortality (NRM). However, we must emphasize the preliminary character of the results of this retrospective
Willasch AM, Peters C, Sedlacek P, Dalle JH, Kitra-Roussou V, Yesilipek A, Wachowiak J, Lankester A, Prete A, Hamidieh AA, Ifversen M, Buechner J, KrivÃÂ¡n G, Hamladji RM, Diaz-de-Heredia C, Skorobogatova E, Michel G, Locatelli F, Bertaina A, Veys P, Dupont S, Or R, GÃÂ¼ngÃÂ¶r T, Aleinikova O, Sufliarska S, Sundin M, Rascon J, Kaare A, Nemet D, Fagioli F, Klingebiel TE, Styczynski J, Bierings M, Nagy K, Abecasis M, Afanasyev B, Ansari M, Vettenranta K, Alseraihy A, Chybicka A, Robinson S, Bertrand Y, Kupesiz A, Ghavamzadeh A, Campos A, Pichler H, Dalissier A, Labopin M, Corbacioglu S, Balduzzi A, Galimard JE, Bader P, EBMT Paediatric Diseases Working Party	Myeloablative conditioning for allo-HSCT in pediatric ALL: FTBI or chemotherapy?-A multicenter EBMT-PDWP study.	Bone marrow transplantation 2020, Epup ahead of print
Although most children with acute lymphoblastic leukemia (ALL) receive fractionated total body irradiation (FTBI) as myeloablative conditioning (MAC) for allogeneic hematopoietic stem cell transplantation (allo-HSCT), it is an important matter of debate if chemotherapy can effectively replace FTBI. To compare outcomes after FTBI versus chemotherapy-based conditioning (CC), we performed a retrospective EBMT registry study. Children aged 2-18 years after MAC for first allo-HSCT of bone marrow (BM) or peripheral blood stem cells (PBSC) from matched-related (MRD) or unrelated donors (UD) in first (CR1) or second remission (CR2) between 2000 and 2012 were included. Propensity score weighting was used to control pretreatment imbalances of the observed variables. 3.054 patients were analyzed. CR1 (1.498): median follow-up (FU) after FTBI (1.285) and CC (213) was 6.8 and 6.1 years. Survivals were not significantly different. CR2 (1.556): median FU after FTBI (1.345) and CC (211) was 6.2 years. Outcomes after FTBI were superior as compared with CC with regard to overall survival (OS), leukemia-free survival (LFS), relapse incidence (RI), and nonrelapse mortality (NRM). However, we must emphasize the preliminary character of the results of this retrospective
de Wilde JRA, van Dooijeweert B, van Vuren AJ, Huisman EJ, Smiers FJ, van der Veer A, van Wijk R, van Solinge WW, Nieuwenhuis EES, van Beers EJ, Bartels M	Transfusion burden in early childhood plays an important role in iron overload in Diamond-Blackfan anaemia.	EJHaem 2022, 3: 1300
In Diamond-Blackfan anaemia (DBA), iron overload (IO) is common in transfusion-dependent patients, yet has also been reported in non-transfusion-dependent patients. We explored the incidence of IO in transfusion-dependent and non-transfusion-dependent DBA patients. We observed hepatic IO in 65% of patients analysed with MRI, including three patients that were only treated with transfusions in the past. Whereas overall ferritin levels and liver iron content correlated, ferritin levels did not reflect total body iron adequately. Our data suggest that transfusion burden in the past plays an important role in IO in DBA, and should be taken into account during follow up.
Willig TN, Draptchinskaia N, Dianzani I, Ball S, Niemeyer C, Ramenghi U, Orfali K, Gustavsson P, Garelli E, Brusco A, Tiemann C, Pérignon JL, Bouchier C, Cicchiello L, Dahl N, Mohandas N, Tchernia G	Mutations in ribosomal protein S19 gene and diamond blackfan anemia: wide variations in phenotypic expression.	Blood 1999, 94: 4294
Mutations of the ribosomal protein S19 (RPS19) gene were recently identified in 10 patients with Diamond Blackfan anemia (DBA). To determine the prevalence of mutations in this gene in DBA and to begin to define the molecular basis for the observed variable clinical phenotype of this disorder, the genomic sequence of the 6 exons and the 5' untranslated region of the RPS19 gene was directly assessed in DBA index cases from 172 new families. Mutations affecting the coding sequence of RPS19 or splice sites were found in 34 cases (19.7%), whereas mutations in noncoding regions were found in 8 patients (4.6%). Mutations included nonsense, missense, splice sites, and frameshift mutations. A hot spot for missense mutations was identified between codons 52 and 62 of the RPS19 gene in a new sequence consensus motif W-[YFW]-[YF]-x-R-[AT]-A-[SA]-x-[AL]-R-[HRK]-[ILV]-Y. No correlation between the nature of mutations and the different patterns of clinical expression, including age at presentation, presence of malformations, and therapeutic outcome, could be documented. Moreover, RPS19 mutations were also found in some first-degree relatives presenting only with isolated high erythrocyte adenosine deaminase activity and/or macrocytosis. The lack of a consistent relationship between the nature of the mutations and the clinical phenotype implies that yet unidentified factors modulate the phenotypic expression of the primary genetic defect in families with RPS19 mutations.
Wimmer K, Zhu X, Lamb B, Kuick R, Ambros P, Kovar H, Thoraval D, Elkahloun A, Meltzer P, Hanash S	Two-dimensional DNA electrophoresis identifies novel CpG islands frequently coamplified with MYCN in neuroblastoma.	Med Pediatr Oncol 2001, 36: 75
Wimmer R, Eckart M, Meyer-Puttlitz B, Fonatsch C, Pietsch T	Mutational and expression analysis of the NF1 gene argues against a role as tumor suppressor in sporadic pilocytic astrocytomas.	J Neuropathol Exp Neurol 2002, 61: 896
Winkler K, Bieling P, Bielack S	Chemotherapy of osteosarcoma.	Z Orthop Ihre Grenzgeb 1992, 130: 285
Winkler K, Bielack S, Delling G, Jürgens H, Kotz R, Salzer-Kuntschik M	Treatment of osteosarcoma.	Cancer Treat Res 1993, 62: 269
Winkler K	Maligne Tumoren des Knochens - Osteosarkoms23.	Hämatologie-Onkologie 1995
Winkler K	Osteosarkom24.	Therapiekonzepte Onkologie 1995
Winter G, Kirschner-Schwabe R, Groeneveld-Krentz S, Escherich G, Möricke A, von Stackelberg A, Stanulla M, Bailey S, Richter L, Steinemann D, Ripperger T, Escudero A, Farah R, Lohi O, Wadt K, Jongmans M, van Engelen N, Eckert C, Kratz CP	Clinical and genetic characteristics of children with acute lymphoblastic leukemia and Li-Fraumeni syndrome.	Leukemia 2021, 35: 1475
No abstract available
Wirth S	Handlungsempfehlung nach der Leitlinie Eisenmangelanämie.	Monatsschr Kinderheilkd 2012, 160: 275–276
Wisoff JH, Sanford RA, Heier LA, Sposto R, Burger PC, Yates AJ, Holmes EJ, Kun LE	Primary neurosurgery for pediatric low-grade gliomas: a prospective multi-institutional study from the Children's Oncology Group.	Neurosurgery 2011, 68: 1548-54; discussion 1554
Central nervous system neoplasms are the most common solid tumors in children, and more than 40% are low-grade gliomas. Variable locations, extent of resection, postoperative neurodiagnostic evaluation, and histology have confounded therapy and outcome.
Witt V	Blutungen und Thromboembolien.	Pädiatrische Onkologie und Hämatologie, Hrsg: Gadner, H, Gaedicke G 2006
Witt V, Pichler H, Fritsch G, Peters C	Multiple small versus few large amount aspirations for bone marrow harvesting in autologous and allogeneic bone marrow transplantation.	Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis 2016, 55: 221
For successful bone marrow transplantation it is necessary to obtain enough progenitor cells during the bone marrow (BM) harvesting procedure. Most centers are using multiple aspirations of maximum 2 ml BM (A), while other centers are using few larger amount aspirations for BM harvesting (B). There is still a discussion about possible differences in graft composition between A and B. To evaluate the feasibility in children we evaluated twenty BM harvestings that were performed in 18 donors, 7 autologous (median age 6.93y; 2.48-16.6) and 13 allogeneic donors (median age 19.75y; 6.45-50.7). A and B were performed crosswise by 2 operators starting with A (2 ml) or B (100 ml) changing to B or A, collecting identically amounts with both methods. We found no statistically significant difference between A and B for MNC, T-cells, and CFU (MNC/ml 824572 versus 725000, p = 0.728; MNC/kg 3.1 107 versus 2.9 107, p = 0.296; CD3/ml 162500 versus 300000, p = 0.310; CFU/105 MNC 1678 versus 1315, p = 0.094), but for CD34+ cells (CD34/kg 2.62 versus 2.09, p = 0.045). BM harvest by the large amount few punctures method (B) is as sufficient as the commonly used small amount frequent punctures method (A), and could be therefore used equally.
Wlodarski MW, Niemeyer CM	Introduction: Genetic syndromes predisposing to myeloid neoplasia.	Seminars in hematology 2017, 54: 57
Wlodarski MW, Da Costa L, O'Donohue MF, Gastou M, Karboul N, Montel-Lehry N, Hainmann I, Danda D, Szvetnik A, Pastor V, Paolini N, di Summa FM, Tamary H, Quider AA, Aspesi A, Houtkooper RH, Leblanc T, Niemeyer CM, Gleizes PE, MacInnes AW	Recurring mutations in RPL15 are linked to hydrops fetalis and treatment independence in Diamond-Blackfan anemia.	Haematologica 2018, 103: 949
Diamond-Blackfan anemia (DBA) is a rare inherited bone marrow failure disorder linked predominantly to ribosomal protein gene mutations. Here the European DBA consortium reports novel mutations identified in the gene in 6 unrelated individuals diagnosed with DBA. Although point mutations have not been previously reported for , we identified 4 individuals with truncating mutations p.Tyr81* (in 3 of 4) and p.Gln29, and 2 with missense variants p.Leu10Pro and p.Lys153Thr. Notably, 75% (3 of 4) of truncating mutation carriers manifested with severe hydrops fetalis and required intrauterine transfusions. Even more remarkable is the observation that the 3 carriers of p.Tyr81 mutation became treatment-independent between four and 16 months of life and maintained normal blood counts until their last follow up. Genetic reversion at the DNA level as a potential mechanism of remission was not observed in our patients. studies revealed that cells carrying mutations have pre-rRNA processing defects, reduced 60S ribosomal subunit formation, and severe proliferation defects. Red cell culture assays of -mutated primary erythroblast cells also showed a severe reduction in cell proliferation, delayed erythroid differentiation, elevated TP53 activity, and increased apoptosis. This study identifies a novel subgroup of DBA with mutations in the gene with an unexpected high rate of hydrops fetalis and spontaneous, long-lasting remission.
Sahoo SS, Pastor VB, Goodings C, Voss RK, Kozyra EJ, Szvetnik A, Noellke P, Dworzak M, Starý J, Locatelli F, Masetti R, Schmugge M, De Moerloose B, Catala A, Kállay K, Turkiewicz D, Hasle H, Buechner J, Jahnukainen K, Ussowicz M, Polychronopoulou S, Smith OP, Fabri O, Barzilai S, de Haas V, Baumann I, Schwarz-Furlan S, European Working Group of MDS in Children (EWOG-MDS), Niewisch MR, Sauer MG, Burkhardt B, Lang P, Bader P, Beier R, Müller I, Albert MH, Meisel R, Schulz A, Cario G, Panda PK, Wehrle J, Hirabayashi S, Derecka M, Durruthy-Durruthy R, Göhring G, Yoshimi-Noellke A, Ku M, Lebrecht D, Erlacher M, Flotho C, Strahm B, Niemeyer CM, Wlodarski MW	Clinical evolution, genetic landscape and trajectories of clonal hematopoiesis in SAMD9/SAMD9L syndromes.	Nature medicine 2021, 27: 1806
Woessmann W, Seidemann K, Mann G, Zimmermann M, Burkhardt B, Oschlies I, Ludwig W, Klingebiel T, Graf N, Gruhn B, Jürgens H, Niggli F, Parwaresch R, Gadner H, Riehm H, Schrappe M, Reiter A	The impact of the methotrexate administration schedule and dose in the treatment of children and adolescents with B-cell neoplasms - a report of the BFM group study NHL-BFM95.	Blood 2004
Wolfl M, Jungbluth AA, Garrido F, Cabrera T, Meyen-Southard S, Spitz R, Ernestus K, Berthold F	Expression of MHC class I, MHC class II, and cancer germline antigens in neuroblastoma.	Cancer immunology, immunotherapy : CII 2005, 54: 400
BACKGROUND: Neuroblastoma is the most common solid extracranial tumor in childhood, still with poor survival rates for metastatic disease. Neuroblastoma cells are of neuroectodermal origin and express a number of cancer germline (CG) antigens. These CG antigens may represent a potential target for immunotherapy such as peptide-based vaccination strategies. OBJECTIVE: The purpose of this study was to analyze the presence of MAGE-A1, MAGE-A3/A6, and NY-ESO-1 on an mRNA and protein level and to determine the expression of MHC class I and MHC class II antigens within the same tumor specimens. METHODS: A total of 68 tumors were available for RT-PCR, and 19/68 tumors were available for immunohistochemical (IHC) analysis of MAGE-A1, MAGE-A3/A6, and NY-ESO-1. In parallel, the same tumors were stained with a panel of antibodies for MHC class I and MHC class II molecules. RESULTS: Screening of 68 tumor specimens by RT-PCR revealed expression of MAGE-A1 in 44%, MAGE-A3/A6 in 21%, and NY-ESO-1 in 28% of cases. Immunohistochemistry for CG antigens of selected tumors showed good agreement between protein and gene expression. However, staining revealed a heterogeneous expression of CG antigens. None of the selected tumors showed MHC class I or MHC class II expression. CONCLUSIONS: mRNA expression of MAGE-A1, MAGE-A3/A6, and NY-ESO-1 is congruent with the protein expression as determined by immunohistochemistry. The heterogeneous CG-antigen expression and the lack of MHC class I and II molecules may have implications for T-cell-mediated immunotherapy in neuroblastoma.
Woessmann W, Seidemann K, Mann G, Zimmermann M, Burkhardt B, Oschlies I, Ludwig WD, Klingebiel T, Graf N, Gruhn B, Jürgens H, Niggli F, Parwaresch R, Gadner H, Riehm H, Schrappe M, Reiter A, BFM Group	The impact of the methotrexate administration schedule and dose in the treatment of children and adolescents with B-cell neoplasms: a report of the BFM Group Study NHL-BFM95.	Blood 2005, 105: 948
Woessmann W, Peters C, Lenhard M, Burkhardt B, Sykora KW, Dilloo D, Kremens B, Lang P, Fuhrer M, Kuhne T, Parwaresch R, Ebell W, Reiter A	Allogeneic haematopoietic stem cell transplantation in relapsed or refractory anaplastic large cell lymphoma of children and adolescents--a Berlin-Frankfurt-Münster group report.	Br J Haematol 2006, 133: 176
Woessmann W, Zimmermann M, Lenhard M, Burkhardt B, Rossig C, Kremens B, Lang P, Attarbaschi A, Mann G, Oschlies I, Klapper W, Reiter A	Relapsed or Refractory Anaplastic Large-Cell Lymphoma in Children and Adolescents After Berlin-Frankfurt-Muenster (BFM)-Type First-Line Therapy: A BFM-Group Study.	J Clin Oncol 2011, [Epub ahead of print]
PURPOSE To evaluate risk factors for outcome in children and adolescents with relapse of anaplastic large-cell lymphoma (ALCL) after comparable first-line therapy. PATIENTS AND METHODS We analyzed a population-based cohort of 74 children with relapsed ALCL after Berlin-Frankfurt-Muenster-type first-line therapy between April 1990 and December 2003. The recommended salvage strategy was reinduction chemotherapy followed by autologous hematopoietic stem-cell transplantation (SCT). Results With a median follow-up time of 8.4 years (range, 4.5 to 16.4 years), the 5-year overall survival (OS) rate after first relapse was 57% ± 6%. Survival correlated with time of relapse and clinically advanced dissemination. Five-year OS of 16 patients who experienced progression during first-line therapy was 25% ± 11% compared with 66% ± 6% for 58 patients with a later relapse (P = .002). Five-year OS of 11 patients with bone marrow or CNS involvement was 27% ± 13% compared with 62% ± 6% for 63 patients without involvement (P = .001). Five-year event-free survival (EFS) and OS of 39 children who received the recommended autologous SCT were 59% ± 8% and 77% ± 7%, respectively. EFS after autologous SCT was significantly associated with time to relapse (progression: n = 3; EFS, 0; later relapse: n = 36; EFS, 64% ± 8%; P = .014) and CD3 expression (CD3 negative: n = 25; EFS, 72% ± 9%; CD3 positive: n = 11; EFS, 18% ± 12%; P < .001), but not with site of relapse, conditioning regimen, or graft manipulation. No relapses occurred among 10 patients with relapsed CD3-positive ALCL treated with allogeneic SCT. CONCLUSION Reinduction chemotherapy followed by autologous SCT proved feasible and efficacious for patients with a first relapse of CD3-negative ALCL after first-line therapy. Patients with progression during first-line therapy or relapsed CD3-positive ALCL may benefit from allogeneic SCT.
Wolff G, Brix J	Bericht über eine Arbeitstagung zum Thema: "Psychosoziale Betreuung onkologisch erkrankter Kinder und ihrer Familien" in Heidelberg vom 3. 10. bis 5. 10. 1980.	Praxis der Kinderpsychologie und Kinderpsychiatrie 30 3, S. 100 - 103
Wolfrom C, Hartmann R, Fengler R, Brühmuller S, Ingwersen A, Henze G	Randomized comparison of 36-hour intermediate-dose versus 4-hour high-dose methotrexate infusions for remission induction in relapsed childhood acute lymphoblastic leukemia.	J Clin Oncol 1993, 11: 827
Wolfrom C, Hartmann R, Brühmuller S, Fengler R, Reiter A, Ritter J, Henze G	Similar outcome in boys with isolated and combined testicular acute lymphoblastic leukemia relapse after stratified BFM salvage therapy.	Haematol Blood Transfus 1996, 38: 647
Wolf J, Schellong G, Diehl V	Breast cancer following treatment of Hodgkin's disease--more reasons for less radiotherapy?	Eur J Cancer 1997, 33: 2293
Wolff J, Hauch H, Kühl J, Egeler R, Jürgens H	Dexamethasone increases hepatotoxicity of MTX in children with brain tumors.	Anticancer Res 1998, 18: 2895
Wolff J, Kühl J, Bamberg M, Krauseneck P	Hirntumoren im Kindesalter.	Kompendium internistische Onkologie 1998,Band 2
Wolfe J, Grier HE, Klar N, Levin SB, Ellenbogen JM, Salem-Schatz S, Emanuel EJ, Weeks JC	Symptoms and suffering at the end of life in children with cancer.	N Engl J Med 2000, 342: 326
Cancer is the second leading cause of death in children, after accidents. Little is known, however, about the symptoms and suffering at the end of life in children with cancer.
Wolff JE, Gnekow AK, Kortmann RD, Pietsch T, Urban C, Graf N, Kühl J	Preradiation chemotherapy for pediatric patients with high-grade glioma.	Cancer 2002, 94: 264
Wolff JEA	Hochgradig maligne Gliome und Ponsgliome im Kindes- und Jugendalter.	Interdisziplinäre Leitlinie der Deutschen Krebsgesellschaft und der Gesellschaft für Pädiatrische Onkologie und Hämatologie 2006
Wolff JE, Kramm C, Kortmann RD, Pietsch T, Rutkowski S, Jorch N, Gnekow A, Driever PH	Valproic acid was well tolerated in heavily pretreated pediatric patients with high-grade glioma.	J Neurooncol 2008, 90: 309
Valproic acid (VPA) inhibits histone deacetylase and has been reported to induce apoptosis in glioma. We report 44 heavily pretreated pediatric patients with high-grade glioma or diffuse intrinsic pontine glioma who received VPA as oral continues maintenance treatment with individual dose adaptation. The tumor status when starting the drug was: no measurable disease in 12, measurable but stable disease in 12, and measurable progressive disease in 22 patients. Average trough blood levels of VPA were 99 mg/l. The most frequent complaint was somnolence (three patients), but no severe toxicity was reported. One relapse patient responded, early progression of disease was observed in three frontline patients and in six relapsed patients. Median overall survival duration for all patients was 1.33 years, with large differences between first-line (5-year overall survival, 44%) and relapse therapy (5-year overall survival, 14%). This shows that valproate is safe in this patient population. The moderate tumor efficacy encourages studying the drug further as an element of multi-agent protocols.
Wolff JE, Berrak S, Koontz Webb SE, Zhang M	Nitrosourea efficacy in high-grade glioma: a survival gain analysis summarizing 504 cohorts with 24193 patients.	J Neurooncol 2008, 88: 57
Even though past studies have suggested efficacy of nitrosourea drugs in patients with high-grade glioma and temozolomide has recently been shown significantly to be beneficial, no conclusive comparisons between these agents have been published. We performed a survival gain analysis of 364 studies describing 24,193 patients with high-grade glioma treated in 504 cohorts, and compared the effects of drugs. The most frequent diagnoses were glioblastoma multiforme (GBM) (72%) and anaplastic astrocytoma (22%). The mean overall survival (mOS) was 14.1 months. The outcome was influenced by several of the known prognostic factors including the histological grade, if the tumors were newly diagnosed or recurrent, the completeness of resection, patients' age, and gender. This information allowed the calculation of a predicted mOS for each cohort based on their prognostic factors independent of treatment. Survival gain to characterize the influence of treatment was subsequently defined and validated as the difference between the observed and the predicted mOS. In 62 CCNU-treated cohorts and 15 ACNU-treated cohorts the survival gain was 5.3 months and 8.9 months (P < 0.0005), respectively. No detectable survival gain for patients treated with various BCNU-containing regimens was found. Conclusion CCNU- and ACNU-containing regimens were superior to BCNU containing regiments.
Wolff JE, Classen CF, Wagner S, Kortmann RD, Palla SL, Pietsch T, Kühl J, Gnekow A, Kramm CM	Subpopulations of malignant gliomas in pediatric patients: analysis of the HIT-GBM database.	J Neurooncol 2008, 87: 155
Abstract Pediatric malignant gliomas represent a heterogeneous group of tumors. This publication reviews data from the first three HIT-GBM protocols. One important question is whether it makes sense to include both histologically confirmed high-grade glial tumors (HGG), and radiologically confirmed diffuse intrinsic pontine gliomas in a single study. Three-hundred-and ten patients (173 male, median age 10.0 years) were enrolled. Tumor locations were cerebral hemispheres: 80, basal ganglia: 38, pons: 134, non-pontine brain stem: 14, cerebellum: 14, spinal: 8, and overlapping areas: 22. Surgical resection was complete in 49, subtotal in 35, partial in 58, biopsy in 99, and no surgery in 69 cases. One-hundred-and twenty-three cases corresponded to WHO grade IV, 101 to III, and 15 to I/II. Two-hundred-and twenty-eight patients could be evaluated for response: CR: 8, PR: 32, SD: 116, and PD: 72. Median overall survival time was 1.03 years, and median event free survival was 0.54 years. Five year OS-rate was 10.28 +/- 2.1%. In the total database, tumor location, grading, and extent of surgical resection were prognostic factors, but the relevance differed in location subgroups with no relevance for sex, histological grading or extend of surgical resection in pontine tumors. Possible prognostic factors were not distributed homogeneously. Pontine tumors differed from cerebral hemisphere tumors concerning the frequency of previous diseases, the age at diagnosis (median age pons 7.9 years versus cerebral hemispheres 11.4 years), and the frequency of WHO grade III versus Grade IV (III:IV = 1.6 for pons, and 0.7 for cerebral hemispheres). We conclude that the biology of pontine glioma differs significantly from other HGG, and clinical studies should be separate with different endpoints.
Wolff JE, Classen CF, Wagner S, Kortmann RD, Palla SL, Pietsch T, Kühl J, Gnekow A, Kramm CM	Subpopulations of malignant gliomas in pediatric patients: analysis of the HIT-GBM database.	Journal of neuro-oncology 2008, 87: 155
Pediatric malignant gliomas represent a heterogeneous group of tumors. This publication reviews data from the first three HIT-GBM protocols. One important question is whether it makes sense to include both histologically confirmed high-grade glial tumors (HGG), and radiologically confirmed diffuse intrinsic pontine gliomas in a single study. Three-hundred-and ten patients (173 male, median age 10.0 years) were enrolled. Tumor locations were cerebral hemispheres: 80, basal ganglia: 38, pons: 134, non-pontine brain stem: 14, cerebellum: 14, spinal: 8, and overlapping areas: 22. Surgical resection was complete in 49, subtotal in 35, partial in 58, biopsy in 99, and no surgery in 69 cases. One-hundred-and twenty-three cases corresponded to WHO grade IV, 101 to III, and 15 to I/II. Two-hundred-and twenty-eight patients could be evaluated for response: CR: 8, PR: 32, SD: 116, and PD: 72. Median overall survival time was 1.03 years, and median event free survival was 0.54 years. Five year OS-rate was 10.28 +/- 2.1%. In the total database, tumor location, grading, and extent of surgical resection were prognostic factors, but the relevance differed in location subgroups with no relevance for sex, histological grading or extend of surgical resection in pontine tumors. Possible prognostic factors were not distributed homogeneously. Pontine tumors differed from cerebral hemisphere tumors concerning the frequency of previous diseases, the age at diagnosis (median age pons 7.9 years versus cerebral hemispheres 11.4 years), and the frequency of WHO grade III versus Grade IV (III:IV = 1.6 for pons, and 0.7 for cerebral hemispheres). We conclude that the biology of pontine glioma differs significantly from other HGG, and clinical studies should be separate with different endpoints.
Wolff JE, Driever PH, Erdlenbruch B, Kortmann RD, Rutkowski S, Pietsch T, Parker C, Metz MW, Gnekow A, Kramm CM	Intensive chemotherapy improves survival in pediatric high-grade glioma after gross total resection: results of the HIT-GBM-C protocol.	Cancer 2010, 116: 705
BACKGROUND: The authors hypothesized that intensified chemotherapy in protocol HIT-GBM-C would increase survival of pediatric patients with high-grade glioma (HGG) and diffuse intrinsic pontine glioma (DIPG). METHODS: Pediatric patients with newly diagnosed HGG and DIPG were treated with standard fractionated radiation and simultaneous chemotherapy (cisplatin 20 mg/m2 x 5 days, etoposide 100 mg/m2 x 3 days, and vincristine, and 1 cycle of cisplatin + etoposide + ifosfamide 1.5 g/m x 5 days [PEI] during the last week of radiation). Subsequent maintenance chemotherapy included further cycles of PEI in Weeks 10, 14, 18, 22, 26, and 30, followed by oral valproic acid. RESULTS: Ninety-seven (pons, 37; nonpons, 60) patients (median age, 10 years; grade IV histology, 35) were treated. Resection was complete in 21 patients, partial in 29, biopsy only in 26, and not performed in 21. Overall survival rates were 91% (standard error of the mean [SE] +/- 3%), 56%, and 19% at 6, 12, and 60 months after diagnosis, respectively. When compared with previous protocols, there was no significant benefit for patients with residual tumor, but the 5-year overall survival rate for patients with complete resection treated on HIT-GBM-C was 63% +/- 12% SE, compared with 17% +/- 10% SE for the historical control group (P = .003, log-rank test). CONCLUSIONS: HIT-GBM-C chemotherapy after complete tumor resection was superior to previous protocols.
Wolff JE, Mohiuddin K, Jorch N, Graf N, Wagner S, Vats T, Gnekow A	Measuring performance status in pediatric patients with brain tumors--experience of the HIT-GBM-C protocol.	Pediatr Blood Cancer 2010, 55: 520
BACKGROUND: Measuring the quality of life or performance status in pediatric neurooncology has proven a challenge. Here, we report in a treatment protocol for pediatric patients with high-grade glioma and diffuse intrinsic pontine glioma. PROCEDURE: The Fertigkeitenskala Münster-Heidelberg (FMH) is a 56-item quantitative measure of health status. The number of yes answers is transformed to age-dependent percentiles. Physicians were also asked the patients' health status by their own judgment on a 1-5 scale: normal, mild handicap, age-normal activity severely reduced but patient not in bed, in bed, and in ICU. RESULTS: Assessments were available from 50 of 97 eligible patients. For 22 patients both questionnaire and the physicians score obtained. At the beginning of the treatment, only 5 patients scored over 40 FMH%, and 4 of these survived. Of 16 patients who initially scored less than 40 FMH%, 15 died. During later assessments, most FMH measures became gradually worse. FMH scores improved in three patients. The physician's judgment was documented at diagnosis and during treatment (n = 50). Per physician, 22% of the patients were normal before chemotherapy, decreasing to 16% in the middle of the protocol. At diagnosis only 16% of patients had severely reduced activity, which increased to 30.6% in the middle of the protocol. The FMH% correlated well with the physicians' judgments (P < 0.005). CONCLUSION: The FMH scale is easily obtained and provides a valid assessment of health status. Patients with poor performance at diagnosis had a poorer prognosis.
Wolff B, Ng A, Roth D, Parthey K, Warmuth-Metz M, Eyrich M, Kordes U, Kortmann R, Pietsch T, Kramm C, Wolff JE	Pediatric high grade glioma of the spinal cord: results of the HIT-GBM database.	Journal of neuro-oncology 2011,Epub ahead of print
Little is known about pediatric spinal cord high grade gliomas (SCHGG) beyond their dismal prognosis. Here, we analyzed the HIT-GBM(®) database for the influence of surgical resection on survival. Between 1991 and 2010 the HIT-GBM group collected data from European children diagnosed with high grade glioma. Patients with the following inclusion criteria were analyzed in this study: astrocytic histology, WHO grade III or IV, age at diagnosis <18 years, and tumor localized to the spinal cord. 28 patients (mean age 11.28 years, 14 male) with primary SCHGG were identified. The tumor sizes were measured by the span across adjacent vertebrae and varied greatly (range: 1-20, median: 4). Histology was classified as WHO grade III in 15 and grade IV in 13 tumors. Of note, the four largest tumors identified were WHO grade III. Surgery was classified as complete resection (n = 6), subtotal resection (STR) (n = 7), partial resection (n = 12) or biopsy only (n = 3). 27 patients received chemotherapy, 22 of which also received radiation. With the mean follow-up time of 2.88 (SD ± 2.95) years, 14 patients were still alive resulting in a median overall survival of 2.5 years (SE ± 1.6). The positive prognostic indicators for overall survival were: age younger than 5 years (P = 0.047), WHO grade III (P = 0.046), absence of necrosis (P = 0.025) and gross total resection (GTR) (P = 0.012). The prognosis of SCHGG might not be as miserable as generally assumed. GTR is of benefit. Larger data sets and meta-analysis are necessary to identify patient sub-groups.
Wolff JE, Rytting ME, Vats TS, Zage PE, Ater JL, Woo S, Kuttesch J, Ketonen L, Mahajan A	Treatment of recurrent diffuse intrinsic pontine glioma: the MD Anderson Cancer Center experience.	Journal of neuro-oncology 2011,Epub ahead of print
Recurrent diffuse intrinsic pontine gliomas (DIPG) are traditionally treated with palliative care since no effective treatments have been described for these tumors. Recently, clinical studies have been emerging, and individualized treatment is attempted more frequently. However, an informative way to compare the treatment outcomes has not been established, and historical control data are missing for recurrent disease. We conducted a retrospective chart review of patients with recurrent DIPG treated between 1998 and 2010. Response progression-free survival and possible influencing factors were evaluated. Thirty-one patients were identified who were treated in 61 treatment attempts using 26 treatment elements in 31 different regimens. The most frequently used drugs were etoposide (14), bevacizumab (13), irinotecan (13), nimotuzumab (13), and valproic acid (13). Seven patients had repeat radiation therapy to the primary tumor. Response was recorded after 58 treatment attempts and was comprised of 0 treatment attempts with complete responses, 7 with partial responses, 20 with stable diseases, and 31 with progressive diseases The median progression-free survival after treatment start was 0.16 years (2 months) and was found to be correlated to the prior time to progression but not to the number of previous treatment attempts. Repeat radiation resulted in the highest response rates (4/7), and the longest progression-free survival. These data provide a basis to plan future clinical trials for recurrent DIPG. Repeat radiation therapy should be tested in a prospective clinical study.
von Wolff M , Dittrich R	Übersicht - Kinderwunsch bei Krebspatientinnen - Beratungs- und Therapiestandards.	TumorDiagn u Ther 2013, 34: 320
Wolffenbuttel BHR, Wouters HJCM, Heiner-Fokkema MR, van der Klauw MM	The Many Faces of Cobalamin (Vitamin B₁₂) Deficiency.	Mayo Clinic proceedings. Innovations, quality & outcomes 2019, 3: 200
Wolff JE, Van Gool SW, Kutluk T, Diez B, Kebudi R, Timmermann B, Garami M, Sterba J, Fuller GN, Bison B, Kordes UR	Final results of the Choroid Plexus Tumor study CPT-SIOP-2000.	Journal of neuro-oncology 2022, 156: 599
Standards for chemotherapy against choroid plexus tumors (CPT) have not yet been established.
Wong FL, Boice JD Jr, Abramson DH, Tarone RE, Kleinerman RA, Stovall M, Goldman MB, Seddon JM, Tarbell N, Fraumeni JF Jr, Li FP	Cancer incidence after retinoblastoma. Radiation dose and sarcoma risk.	JAMA : the journal of the American Medical Association 1997, 278: 1262
CONTEXT: There is a substantial risk of a second cancer for persons with hereditary retinoblastoma, which is enhanced by radiotherapy. OBJECTIVE: To examine long-term risk of new primary cancers in survivors of childhood retinoblastoma and quantify the role of radiotherapy in sarcoma development. DESIGN: Cohort incidence study of patients with retinoblastoma followed for a median of 20 years, and nested case-control study of a radiation dose-response relationship for bone and soft tissue sarcomas. SETTING/PARTICIPANTS: A total of 1604 patients with retinoblastoma who survived at least 1 year after diagnosis, identified from hospital records in Massachusetts and New York during 1914 to 1984. RESULTS: Incidence of subsequent cancers was statistically significantly elevated only in the 961 patients with hereditary retinoblastoma, in whom 190 cancers were diagnosed, vs 6.3 expected in the general population (relative risk [RR], 30 [95% confidence interval, 26-47]). Cumulative incidence (+/-SE) of a second cancer at 50 years after diagnosis was 51.0% (+/-6.2%) for hereditary retinoblastoma, and 5.0% (+/-3.0%) for nonhereditary retinoblastoma. All 114 sarcomas of diverse histologic types occurred in patients with hereditary retinoblastoma. For soft tissue sarcomas, the RRs showed a stepwise increase at all dose categories, and were statistically significant at 10 to 29.9 Gy and 30 to 59.9 Gy. A radiation risk for all sarcomas combined was evident at doses above 5 Gy, rising to 10.7-fold at doses of 60 Gy or greater (P<.05). CONCLUSIONS: Genetic predisposition has a substantial impact on risk of subsequent cancers in retinoblastoma patients, which is further increased by radiation treatment. A radiation dose-response relationship is demonstrated for all sarcomas and, for the first time in humans, for soft tissue sarcomas. Retinoblastoma patients should be examined for new cancers and followed into later life to determine whether their extraordinary cancer risk extends to common cancers of adulthood.
Wood I	School.	In: Goldmann A, Hain R, Liben S (eds) Oxford textbook of palliative care in children 2006, pp129
Worch J, Ranft A, DuBois SG, Paulussen M, Jürgens H, Dirksen U	Age dependency of primary tumor sites and metastases in patients with Ewing sarcoma.	Pediatric blood & cancer 2018, 65:e27251
The median age of patients with Ewing sarcoma (EwS) at diagnosis is around 14-15 years. Older age is associated with a worse outcome. The correlation of age at diagnosis on sites of disease has not been fully described.
Worawongsakul R, Steinmeier T, Lin YL, Bauer S, Hardes J, Hecker-Nolting S, Dirksen U, Timmermann B	Proton Therapy for Primary Bone Malignancy of the Pelvic and Lumbar Region - Data From the Prospective Registries ProReg and KiProReg.	Frontiers in oncology 2022, 12: 805051
Multimodality treatments together with local proton therapy (PT) are commonly used in unresectable primary bone malignancies in order to provide better tumor control rate while maintaining good feasibility. The aim of this study is to provide data on outcome of PT for the challenging cohort of pelvic and lumbar bone tumors.
Wossmann W, Schrappe M, Meyer U, Zimmermann M, Reiter A	Incidence of tumor lysis syndrome in children with advanced stage Burkitt's lymphoma/leukemia before and after introduction of prophylactic use of urate oxidase.	Annals Hematology 2003, 82: 160
Wrede B, Liu P, Wolff JE	Chemotherapy improves the survival of patients with choroid plexus carcinoma: a meta-analysis of individual cases with choroid plexus tumors.	J Neurooncol 2007, 85: 345
Abstract BACKGROUND: Choroid plexus carcinomas (CPC) are rare brain tumors with a dismal prognosis. Although the role of surgery has been well established, the question of whether chemotherapy improves the prognosis is still under discussion. METHODS: We created a database of all cases of choroid plexus tumors (CPT) reported in the literature up to the year 2004 to determine prognostic factors and different therapeutic modalities. This database was validated by comparison with an existing database of cases until 1997. RESULTS: Of 857 documented cases of CPT (median patient age at diagnosis, 3 years), 347 were CPC, 15 atypical choroid plexus papilloma (APP), and 495 choroid plexus papilloma (CPP). Histology was a significant prognostic factor (P < .0001; log rank). Within the subgroup of patients with CPC, both surgery and irradiation were linked to a better prognosis (P < .005). The 104 CPC patients who received chemotherapy had a statistically better survival than those without chemotherapy (P = .0004). When subgroups were defined by radiation treatment, chemotherapy remained beneficial in the subgroup of nonirradiated tumors (P = .0001). The benefit of chemotherapy was also significant when the analysis was restricted to the subgroup of patients with less than completely resected CPC (2-year overall survival (OS) 54.8 +/- 7% (standard deviation (SD) vs. 24.4 +/- 7%, P < .0001) and when this subgroup was further divided into smaller subgroups. Likewise, in a multivariate analysis, chemotherapy was highly significantly linked to better prognosis (P = .0001). CONCLUSION: Patients with less than completely resected CPC should receive chemotherapy.
Wrede B, Hasselblatt M, Peters O, Thall PF, Kutluk T, Moghrabi A, Mahajan A, Rutkowski S, Diez B, Wang X, Pietsch T, Kortmann RD, Paulus W, Jeibmann A, Wolff JE	Atypical choroid plexus papilloma: clinical experience in the CPT-SIOP-2000 study.	J Neurooncol 2009, 95: 383
Atypical choroid plexus papilloma (APP) represents a novel intermediate-grade subtype of choroid plexus tumor (CPT), the clinical outcome of which has not been described yet. We present the first analysis of a group of APP patients enrolled in the ongoing CPT-SIOP-2000 study of CPTs. A worldwide registration and a randomized trial for those patients who require chemotherapy started in 2000. For APP, maximal surgical resection was recommended. After surgery, patients who had undergone complete resection were observed, whereas patients with incompletely resected or metastasized APP were treated with six chemotherapy courses (etoposide and vincristine, combined with either carboplatin or cyclophosphamide). Risk-adapted radiotherapy was given only to patients older than 3 years of age. Of the 106 patients with a centrally confirmed CPT histology, 30 had APP, 42 CPP and 34 CPC. APP patients were significantly younger (median = 0.7 years) than patients with CPP or CPC (both medians = 2.3 years). Complete resection was achieved in 68 (64%) patients (79% in CPP, 63% in APP, and 47% in CPC). Metastases were present at diagnosis in 17% of APP patients, 5% of CPP patients, and 21% of CPC patients. All nine APP patients who received postoperative chemotherapy showed an early response after two cycles: two had complete remission, four had partial response, and three had stable disease. In the observation group of 15 patients, one event was seen, and all patients were alive. In the treatment group, one patient with a metastasized tumor and incompletely resected APP died. While APP was defined histologically, median percentages of both the Ki-67/MIB-1 proliferation marker and the p53 tumor suppressor protein increased across the three histological subtypes (from CPP to APP and then CPC), suggesting that the subtypes comprise an ordinal categorization of increasingly severe CPT tumors. This ordering was reiterated by clinical outcome in the 92 patients treated per the study protocol, with 5-year EFS rates of 92% in 39 CPP patients, 83% in 24 APP patients, and 28% in 29 CPC patients. A similar ordering was seen when all 106 patients were evaluated for EFS. APP responded favorably to chemotherapy. The intermediate position of APP between CPP and CPC was supported by the clinical data.
Wrobel G, Mauguen A, Rosolen A, Reiter A, Williams D, Horibe K, Brugières L, Le Deley MC, on behalf of European Inter-Group for Childhood, Non-Hodgkin Lymphoma (EICNHL)	Safety assessment of intensive induction therapy in childhood anaplastic large cell lymphoma: Report of the ALCL99 randomised trial.	Pediatr Blood Cancer 2011, Epub ahead of print
BACKGROUND: ALCL99 protocol including six courses of chemotherapy derived from the NHL-BFM protocol is widely used for the treatment of paediatric anaplastic large-cell lymphoma. In the ALCL99 trial, patients were randomised to receive MTX 1 g/m(2) in 24 hr with intrathecal injection (MTX1) versus MTX 3 g/m(2) in 3 hr without intrathecal (MTX3); then to receive or not vinblastine (high-risk patients). The present study provides information about the acute adverse reactions (ARs) during the six courses of the ALCL99 treatment, assesses risk factors for ARs and evaluates the risk of overweight related to treatment. METHODS: Data concerning ARs were assessed using CTCv2 and analysed overall and according to the type of course. RESULTS: Between 1999 and 2005, 352 patients were recruited. Toxicity assessed after 2050 courses included grade 4 neutropaenia (70% of courses), grade 3-4 stomatitis (13%), grade 3-4 transaminase elevation (10%) and grade 3-4 infection (5%). Four patients (1%) died of toxicity. The toxicity profile differed between courses-A (significantly more haematological toxicity) and courses-B (significantly more stomatitis). The percentage of ARs was higher after the first course than after subsequent courses. Severe toxicity was more frequent after MTX1 than after MTX3 courses but did not differ between courses with or without vinblastine. Overall 20% of patients had a weight gain exceeding 20%. CONCLUSIONS: The high rate of acute toxicity should be considered when using the ALCL99 protocol. Chemotherapy including MTX 3 g/m(2) in 3 hr was less toxic than the same regimen with MTX 1 g/m(2) in 24 hr. Adding vinblastine did not increase the risk of toxicity
Wruck W, Bremmer F, Kotthoff M, Fichtner A, Skowron MA, Schönberger S, Calaminus G, Vokuhl C, Pfister D, Heidenreich A, Albers P, Adjaye J, Nettersheim D	The pioneer and differentiation factor FOXA2 is a key driver of yolk-sac tumour formation and a new biomarker for paediatric and adult yolk-sac tumours.	Journal of cellular and molecular medicine 2021, 25: 1394
Yolk-sac tumours (YSTs), a germ cell tumour subtype, occur in newborns and infants as well as in young adults of age 14-44 years. In clinics, adult patients with YSTs face a poor prognosis, as these tumours are often therapy-resistant and count for many germ cell tumour related deaths. So far, the molecular and (epi)genetic mechanisms that control development of YST are far from being understood. We deciphered the molecular and (epi)genetic mechanisms regulating YST formation by meta-analysing high-throughput data of gene and microRNA expression, DNA methylation and mutational burden. We validated our findings by qRT-PCR and immunohistochemical analyses of paediatric and adult YSTs. On a molecular level, paediatric and adult YSTs were nearly indistinguishable, but were considerably different from embryonal carcinomas, the stem cell precursor of YSTs. We identified FOXA2 as a putative key driver of YST formation, subsequently inducing AFP, GPC3, APOA1/APOB, ALB and GATA3/4/6 expression. In YSTs, WNT-, BMP- and MAPK signalling-related genes were up-regulated, while pluripotency- and (primordial) germ cell-associated genes were down-regulated. Expression of FOXA2 and related key factors seems to be regulated by DNA methylation, histone methylation / acetylation and microRNAs. Additionally, our results highlight FOXA2 as a promising new biomarker for paediatric and adult YSTs.
Wu S, Korte A, Gessner R, Henze G, Seeger K	Levels of the soluble, 55-kilodalton isoform of tumor necrosis factor receptor in bone marrow are correlated with the clinical outcome of children with acute lymphoblastic leukemia in first recurrence.	Cancer 2003, 98: 625
Wuchter C, Harbott J, Schoch C, Schnittger S, Borkhardt A, Karawajew L, Ratei R, Ruppert V, Haferlach T, Creutzig U, Dorken B, Ludwig W	Detection of acute leukemia cells with mixed lineage leukemia (MLL) gene rearrangements by flow cytometry using monoclonal antibody 7. 1	Leukemia 2000, 14: 1232
Wuchter C, Karawajew L, Ruppert V, Schrappe M, Harbott J, Ratei R, Dorken B, Ludwig W	Constitutive expression levels of CD95 and Bcl-2 as well as CD95 function and spontaneous apoptosis in vitro do not predict the response to induction chemotherapy and relapse rate in childhood acute lymphoblastic leukaemia.	Br J Haematol 2000, 110: 154
Wuchter C, Leonid K, Ruppert V, Schrappe M, Buchner T, Schoch C, Haferlach T, Harbott J, Ratei R, Dorken B, Ludwig W	Clinical significance of P-glycoprotein expression and function for response to induction chemotherapy, relapse rate and overall survival in acute leukemia.	haematologica 2000, 85: 711
Wuchter C, Ratei R, Spahn G, Schoch C, Harbott J, Schnittger S, Haferlach T, Creutzig U, Sperling C, Karawajew L, Ludwig W	Impact of CD133 (AC133) and CD90 expression analysis for acute leukemia immunophenotyping.	haematologica 2001, 86: 154
Wuchter C, Ruppert V, Schrappe M, Dorken B, Ludwig W, Karawajew L	In vitro susceptibility to dexamethasone- and doxorubicin-induced apoptotic cell death in context of maturation stage, responsiveness to interleukin 7, and early cytoreduction in vivo in childhood T-cell acute lymphoblastic leukemia.	Blood 2002, 99: 4109
Wuerthwein G, Lanvers-Kaminsky C, Gerss J, Moericke A, Zimmermann M, Stary J, Smisek P, Attarbaschi A, Nath C, Zucchetti M, Rizzari C, Schrappe M, Boos J	Therapeutic Drug Monitoring of Asparaginase: Intra-individual Variability and Predictivity in Children With Acute Lymphoblastic Leukemia Treated With PEG-Asparaginase in the AIEOP-BFM Acute Lymphoblastic Leukemia 2009 Study.	Therapeutic drug monitoring 2020, 42: 435
Therapeutic drug monitoring (TDM) can identify patients with subtherapeutic asparaginase (ASNase) activity [silent inactivation (SI)] and prospectively guide therapeutic adaptation. However, limited intra-individual variability is a precondition for targeted dosing and the diagnosis of SI.
Wutz D, Shayan P, Schmahl G, Mild G, Feil B, Roll S, Kontny H, Niemeyer C	Gene expression of the hematopoietic cell phosphatase in juvenile myelomonocytic leukemia.	Leuk Lymphoma 1999, 35: 491
Wykes C, Arasaretnam A, O'Driscoll S, Farnham L, Moniz C, Rees DC	Vitamin D deficiency and its correction in children with sickle cell anaemia.	Annals of hematology 2014,
Vitamin D deficiency is common in sickle cell anaemia (SCA, HbSS), although its significance and optimal means of correction are unknown. We conducted an audit to assess the clinical significance of 25-hydroxy vitamin D (25-OHD) deficiency in children with SCA and to evaluate two methods of vitamin D supplementation. We audited 25-OHD levels in 81 children with SCA and looked for statistical associations with biochemical, haematological and clinical parameters. In a separate group of regularly transfused children with SCA, we compared changes in 25-OHD blood concentrations following treatment with either high-dose intramuscular ergocalciferol (n = 15) or 4 days of high-dose oral cholecalciferol (n = 64). Ninety-one percent of children with SCA had 25-OHD levels <20 μg/L. The 25-OHD levels were negatively correlated with increasing age (P < 0.001) but showed no significant relationship to laboratory measurements, transcranial Doppler velocities or hospital attendance. Both intramuscular ergocalciferol and oral cholecalciferol supplementations resulted in increases of 25-OHD blood concentration to normal levels. The mean dose of ergocalciferol was greater than that of cholecalciferol (7,729 versus 5,234 international units (IU)/kg, P < 0.001), but the increment in 25-OHD levels was significantly greater in the oral cholecalciferol group (6.44 versus 2.82 (ng/L)/(IU/kg), P < 0.001). Both approaches resulted in vitamin D sufficiency for about 120 days. Increased 25-OHD concentration was significantly associated with increased serum calcium concentration. Vitamin D deficiency is very common in SCA and can be effectively corrected with high-dose intramuscular ergocalciferol or 4 days of high-dose oral cholecalciferol. Prospective, randomised studies are needed to assess the clinical value of vitamin D supplementation.
Wölfl M, Schalk S, Hellmich M, Huster K, Busch D, Berthold F	Quantitation of MHC tetramer-positive cells from whole blood.	Cytometry 2004, 57A: 120
Würthwein G, Krümpelmann S, Tillmann B, Real E, Schulze-Westhoff P, Jürgens H, Boos J	Population pharmacokinetic approach to compare oral and i. v. administration of etoposide.	Anticancer Drugs 1999, 10: 807
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