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Dive into the research topics where Helmut Gadner is active.

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Featured researches published by Helmut Gadner.


Medical and Pediatric Oncology | 1997

Contemporary classification of histiocytic disorders

Blaise E. Favara; Alfred C. Feller; Macro Pauli; Elaine S. Jaffe; Lawrence M. Weiss; Maurizio Aricò; Peter Bucsky; R. Maarten Egeler; Göran Elinder; Helmut Gadner; Mary V. Gresik; Jan-Inge Henter; Shinsaku Imashuku; Gritta E. Janka-Schaub; Ron Jaffe; Stephan Ladisch; Christian Nezelof; Jon Pritchard

Pathologists and pediatric hematologist/ oncologists of the World Health Organizations Committee on Histiocytic/Reticulum Cell Proliferations and the Reclassification Working Group of the Histiocyte Society present a classification of the histiocytic disorders that primarily affect children. Nosology, based on the lineage of lesional cells and biological behavior, is related to the ontogeny of histiocytes (macrophages and dendritic cells of the immune system). Dendritic cell-related disorders of varied biological behavior are dominated by Langerhans cell histiocytosis, but separate secondary proliferations of dendritic cells must be differentiated. Juvenile xanthogranuloma represents a disorder of dermal dendrocytes, another dendritic cell of skin. The hemophagocytic syndromes are the most common of the macrophage-related disorders of varied biological behavior. Guidelines for distinguishing the exceedingly rare malignant diseases of histiocytes from large cell lymphomas through the use of a battery of special studies are provided.


Cancer | 1991

MIC2 is a specific marker for ewing's sarcoma and peripheral primitive neuroectodermal tumors. Evidence for a common histogenesis of ewing's sarcoma and peripheral primitive neuroectodermal tumors from MIC2 expression and specific chromosome aberration

Inge M. Ambros; Peter F. Ambros; Sabine Strehl; Heinrich Kovar; Helmut Gadner; Mechthild Salzer-Kuntschik

This study reports on the specific expression of the MIC2 gene, a pseudoautosomal gene located on the short arms of the X and Y chromosomes, on Ewings sarcoma (ES) and peripheral primitive neuroectodermal tumor (pPNET) cells. The gene product, a cell membrane protein, is recognized by the newly established monoclonal antibody (MoAb) HBA‐71 and the previously described MoAb 12E7 and RFB‐1. Furthermore, the reaction pattern of the MIC2 antibodies, especially HBA‐71, with normal tissues and a great number of benign and malignant tumors (70 different tumors, 199 tumor samples), as well as the correlation between the specific chromosomal aberrations, i.e., the t(11;22) and the del(22) and the expression of this antigen, are demonstrated. Both ES and pPNET cells express the MIC2 gene in very high amounts, which represents a highly selective and almost unique feature of these cells, making an assignment of these tumors in one entity even more likely. The MIC2 antibodies are of great value for clinical and research purposes.


Leukemia | 2000

Long-term results of four consecutive trials in childhood ALL performed by the ALL-BFM study group from 1981 to 1995

M Schrappe; Alfred Reiter; Martin Zimmermann; Jochen Harbott; W.-D. Ludwig; Günter Henze; Helmut Gadner; Odenwald E; Hansjörg Riehm

Four thousand, four hundred and forty eligible children of up to 18 years of age were treated in four consecutive trials between 1981 and 1995 with the treatment protocols of the Berlin–Frankfurt–Münster (BFM) study group for childhood acute lymphoblastic leukemia (ALL). The probability for event-free survival (pEFS) at 8 years improved from 65.8% in study ALL-BFM 81 to 75.9% in study ALL-BFM 90. The cumulative incidence of recurrences with CNS involvement was 10.1% and 9.3% in studies ALL-BFM 81 and 83, but was reduced to less than 5% in study ALL-BFM 90 (for isolated CNS relapses from 5.3% in study ALL-BFM 81 to 1.1% in study ALL-BFM 90). Four major findings were derived from this series of trials performed by 37 to 96 centers in Germany, Austria, and Switzerland: (1) Reintensification is a crucial part of treatment, even in low risk patients; (2) presymptomatic cranial radiotherapy can be safely reduced to 12 Gy, or even be eliminated if it is replaced by early intensive systemic and intrathecal methotrexate applied; (3) maintenance therapy given a total of 24 months from diagnosis provides a lower rate of systemic relapses than treatment for 18 months; (4) inadequate response to an initial 7-day prednisone window (combined with one intrathecal injection of methotrexate on day 1) defines about 10% of the patients with a very high risk of relapse. For patients with adequate early response (90% of all) an 8-year pEFS of 80% has been achieved in the most recent trial ALL-BFM 90. While it has proven so far to be impossible to improve the outcome for the small group of high risk patients, the number of recurrences could be effectively reduced for the large group of patients responding adequately to the prednisone in vivo sensitivity test. Apart from inadequate prednisone response, patients with hyperleukocytosis, age <1 year, or the presence of the Philadelphia-chromosome (Ph+ ALL) are at a particularly high risk of failure.


Journal of Clinical Oncology | 2003

Primary Metastatic Osteosarcoma: Presentation and Outcome of Patients Treated on Neoadjuvant Cooperative Osteosarcoma Study Group Protocols

Leo Kager; Andreas Zoubek; Ulrike Pötschger; Ulrike Kastner; Silke Flege; Beate Kempf-Bielack; Detlev Branscheid; Rainer Kotz; Mechthild Salzer-Kuntschik; Winfried Winkelmann; Gernot Jundt; Hartmut Kabisch; Peter Reichardt; Heribert Jürgens; Helmut Gadner; Stefan S. Bielack

PURPOSE To determine demographic data and define prognostic factors for long-term outcome in patients presenting with high-grade osteosarcoma of bone with clinically detectable metastases at initial presentation. PATIENTS AND METHODS Of 1,765 patients with newly diagnosed, previously untreated high-grade osteosarcomas of bone registered in the neoadjuvant Cooperative Osteosarcoma Study Group studies before 1999, 202 patients (11.4%) had proven metastases at diagnosis and therefore were enrolled onto an analysis of demographic-, tumor-, and treatment-related variables, response, and survival. The intended therapeutic strategy included pre- and postoperative multiagent chemotherapy as well as aggressive surgery of all resectable lesions. RESULTS With a median follow-up of 1.9 years (5.5 years for survivors), 60 patients were alive, 37 of whom were in continuously complete surgical remission. Actuarial overall survival rates at 5 and 10 (same value for 15) years were 29% (SE = 3%) and 24% (SE = 4%), respectively. In univariate analysis, survival was significantly correlated with patient age, site of the primary tumor, number and location of metastases, number of involved organ systems, histologic response of the primary tumor to preoperative chemotherapy, and completeness and time point of surgical resection of all tumor sites. However, after multivariate Cox regression analysis, only multiple metastases at diagnosis (relative hazard rate [RHR] = 2.3) and macroscopically incomplete surgical resection (RHR = 2.4) remained significantly associated with inferior outcomes. CONCLUSION The number of metastases at diagnosis and the completeness of surgical resection of all clinically detected tumor sites are of independent prognostic value in patients with proven primary metastatic osteosarcoma.


Blood | 2008

Risk-Adjusted Therapy of Acute Lymphoblastic Leukemia Can Decrease Treatment Burden and Improve Survival: Treatment Results of 2169 Unselected Pediatric and Adolescent Patients Enrolled in the Trial ALL-BFM 95.

Anja Möricke; Alfred Reiter; Martin Zimmermann; Helmut Gadner; Martin Stanulla; Michael Dördelmann; Lutz Löning; Rita Beier; Wolf-Dieter Ludwig; Richard Ratei; Jochen Harbott; Joachim Boos; Georg Mann; Felix Niggli; Andreas Feldges; Günter Henze; Karl Welte; J.D. Beck; Thomas Klingebiel; Charlotte M. Niemeyer; Felix Zintl; Udo Bode; Christian Urban; Helmut Wehinger; Dietrich Niethammer; H. Riehm; Martin Schrappe

The trial ALL-BFM 95 for treatment of childhood acute lymphoblastic leukemia was designed to reduce acute and long-term toxicity in selected patient groups with favorable prognosis and to improve outcome in poor-risk groups by treatment intensification. These aims were pursued through a stratification strategy using white blood cell count, age, immunophenotype, treatment response, and unfavorable genetic aberrations providing an excellent discrimination of risk groups. Estimated 6-year event-free survival (6y-pEFS) for all 2169 patients was 79.6% (+/- 0.9%). The large standard-risk (SR) group (35% of patients) achieved an excellent 6y-EFS of 89.5% (+/- 1.1%) despite significant reduction of anthracyclines. In the medium-risk (MR) group (53% of patients), 6y-pEFS was 79.7% (+/- 1.2%); no improvement was accomplished by the randomized use of additional intermediate-dose cytarabine after consolidation. Omission of preventive cranial irradiation in non-T-ALL MR patients was possible without significant reduction of EFS, although the incidence of central nervous system relapses increased. In the high-risk (HR) group (12% of patients), intensification of consolidation/reinduction treatment led to considerable improvement over the previous ALL-BFM trials yielding a 6y-pEFS of 49.2% (+/- 3.2%). Compared without previous trial ALL-BFM 90, consistently favorable results in non-HR patients were achieved with significant treatment reduction in the majority of these patients.


Cancer | 1988

Multidisciplinary treatment of primary Ewing's sarcoma of bone. A 6‐year experience of a European cooperative trial

H. Jürgens; Ulrich Exner; Helmut Gadner; Dieter Harms; Jörg Michaelis; Rolf Sauer; J. Treuner; Tom Voûte; Winfried Winkelmann; Kurt Winkler; U. Göbel

The German Society of Pediatric Oncology in 1981 initiated the Cooperative Ewings Sarcoma Study (CESS 81) using a four‐drug combination of chemotherapy prior to definitive local control with surgery and/or radiation. From January 1, 1981 until February 28, 1985, 93 patients were registered at the trial office from 54 participating institutions in West Germany, Austria, Switzerland, and the Netherlands. On February 1, 1987, 54 of 93 patients were disease‐free. Using the Kaplan‐Meier life table analysis, the estimated disease‐free survival (DPS) rate was 60% at 36 months and 55% at 69 months. The median period of observation was 29 months, ranging from 22 months to 69 months. Twenty‐one of 93 patients (23%) had local failure, 18 of 93 patients (19%) developed systemic metastases. The local failure rate was particularly high in patients treated with radiation and was reduced when radiation planning was centralized within the study based upon the extent of disease at diagnosis. Cox regression analysis of prognostic factors showed that tumor volume was a significant factor influencing prognosis. The estimated 3‐year DFS rate was 80% for patients with small tumors (volume less than 100 ml) compared to 31% for patients with large tumors (volume greater than or equal to 100 ml). In patients who had surgery for local control, the histologic response to chemotherapy was analyzed on the surgical specimen and had a strong influence on survival: 79% DFS at 3 years for patients with less than 10% viable tumor (good responders) compared to 31% DFS for patients with more than 10% viable tumor (poor responders). Tumor load and responsiveness to chemotherapy are the two major factors influencing prognosis in patients with primary Ewings sarcoma of bone.


Medical and Pediatric Oncology | 1997

HLH‐94: A treatment protocol for hemophagocytic lymphohistiocytosis

Jan-Inge Henter; Maurizio Aricò; R. Maarten Egeler; Göran Elinder; Blaise E. Favara; Alexandra H. Filipovich; Helmut Gadner; Shinsaku Imashuku; Gritta E. Janka-Schaub; Diane M. Komp; Stephan Ladisch; David Webb

In January 1995, the Hemophagocytic Lymphohistiocytosis (HLH) Study Group opened its first international treatment study dedicated to the hemophagocytic lymphohistiocytoses. The main intention of the study protocol is to offer affected children therapy with a wellestablished chemotherapeutic regimen (epipodophyllotoxin and corticosteroids) in combinationwith a newer approach, immunotherapy with cyclosporin A. Subsequent bone marrow transplantation (BMT) is recommended to all children with an available donor. The purpose of this communication is to describe this approach to management, that intends to prolong survival and increase the cure rate for children throughout the world with this highly lethal disease [1].


Leukemia | 2010

Long-term results of five consecutive trials in childhood acute lymphoblastic leukemia performed by the ALL-BFM study group from 1981 to 2000

Anja Möricke; Martin Zimmermann; Alfred Reiter; G Henze; André Schrauder; Helmut Gadner; W.-D. Ludwig; J. Ritter; Jochen Harbott; Georg Mann; Thomas Klingebiel; F Zintl; C. Niemeyer; Bernhard Kremens; Felix Niggli; D Niethammer; Karl Welte; Martin Stanulla; E Odenwald; Hansjörg Riehm; M Schrappe

Between 1981 and 2000, 6609 children (<18 years of age) were treated in five consecutive trials of the Berlin–Frankfurt–Münster (BFM) study group for childhood acute lymphoblastic leukemia (ALL). Patients were treated in up to 82 centers in Germany, Austria and Switzerland. Probability of 10-year event-free survival (EFS) (survival) improved from 65% (77%) in study ALL-BFM 81 to 78% (85%) in ALL-BFM 95. In parallel to relapse reduction, major efforts focused on reducing acute and late toxicity through advanced risk adaptation of treatment. The major findings derived from these ALL-BFM trials were as follows: (1) preventive cranial radiotherapy could be safely reduced to 12 Gy in T-ALL and high-risk (HR) ALL patients, and eliminated in non- HR non-T-ALL patients, if it was replaced by high-dose and intrathecal (IT) MTX; (2) omission of delayed re-intensification severely impaired outcome of low-risk patients; (3) 6-month-less maintenance therapy caused an increase in systemic relapses; (4) slow response to an initial 7-day prednisone window was identified as adverse prognostic factor; (5) condensed induction therapy resulted in significant improvement of outcome; (6) the daunorubicin dose in induction could be safely reduced in low-risk patients and (7) intensification of consolidation/re-intensification treatment led to considerable improvement of outcome in HR patients.


Leukemia | 2008

Minimal residual disease-directed risk stratification using real-time quantitative PCR analysis of immunoglobulin and T-cell receptor gene rearrangements in the international multicenter trial AIEOP-BFM ALL 2000 for childhood acute lymphoblastic leukemia

Thomas Flohr; André Schrauder; G Cazzaniga; Renate Panzer-Grümayer; V H J van der Velden; S Fischer; Martin Stanulla; G Basso; Felix Niggli; Beat W. Schäfer; Rosemary Sutton; Rolf Koehler; Martin Zimmermann; Maria Grazia Valsecchi; Helmut Gadner; Giuseppe Masera; M Schrappe; J J M van Dongen; Andrea Biondi; Claus R. Bartram

Detection of minimal residual disease (MRD) is the most sensitive method to evaluate treatment response and one of the strongest predictors of outcome in childhood acute lymphoblastic leukemia (ALL). The 10-year update on the I-BFM-SG MRD study 91 demonstrates stable results (event-free survival), that is, standard risk group (MRD-SR) 93%, intermediate risk group (MRD-IR) 74%, and high risk group (MRD-HR) 16%. In multicenter trial AIEOP-BFM ALL 2000, patients were stratified by MRD detection using quantitative PCR after induction (TP1) and consolidation treatment (TP2). From 1 July 2000 to 31 October 2004, PCR target identification was performed in 3341 patients: 2365 (71%) patients had two or more sensitive targets (⩽10−4), 671 (20%) patients revealed only one sensitive target, 217 (6%) patients had targets with lower sensitivity, and 88 (3%) patients had no targets. MRD-based risk group assignment was feasible in 2594 (78%) patients: 40% were classified as MRD-SR (two sensitive targets, MRD negativity at both time points), 8% as MRD-HR (MRD ⩾10−3 at TP2), and 52% as MRD-IR. The remaining 823 patients were stratified according to clinical risk features: HR (n=108) and IR (n=715). In conclusion, MRD-PCR-based stratification using stringent criteria is feasible in almost 80% of patients in an international multicenter trial.


Journal of Clinical Oncology | 1996

Does expression of different EWS chimeric transcripts define clinically distinct risk groups of Ewing tumor patients

Andreas Zoubek; B. Dockhorn-Dworniczak; Olivier Delattre; H Christiansen; F Niggli; I Gatterer-Menz; T L Smith; Heribert Jürgens; Helmut Gadner; Heinrich Kovar

PURPOSE Because of the high heterogeneity of EWS gene fusions with FLI1 and ERG genes due to variable chromosomal breakpoint locations in Ewing tumors (ET) (14 different chimeric transcripts identified so far), we evaluated the clinical impact of the expression of diverse fusion transcripts in ET patients. PATIENTS AND METHODS In a European multicenter study, 147 ET were analyzed by reverse-transcriptase polymerase chain reaction (RT-PCR) and the molecular data statistically compared with all clinical data available. RESULTS Most tumors expressed chimeric transcripts with fusion of EWS exon 7 to FLI1 exon 6 (75 of 147) (type I) or five (39 of 147) and EWS exon 10 to FLI1 exon 5 (eight of 147) or 6 (five of 147). In five cases, chimerism between EWS exon 9 and FLI1 exons 4 and EWS exon 7 and FLI1 exon 7 or 8 was observed. Fifteen cases of EWS-ERG rearrangement were identified. In 85 of these patients treated in the European Cooperative Ewing Sarcoma Studies, molecular results were analyzed in comparison to age, sex, tumor localization, tumor volume, and disease extension. No significant correlation between the various fusion types and these features were observed. Relapse-free survival (RFS) for the 31 patients with localized disease and fusion type I tended to be longer compared with the 24 patients with localized tumors bearing other chimeric transcripts (P = .04). CONCLUSION Results suggest a possible advantage in PFS for patients with localized disease and fusion type I transcripts, although this will require prospective validation with a larger number of patients and longer follow-up periods.

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Georg Mann

Medical University of Vienna

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Oskar A. Haas

Boston Children's Hospital

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Andreas Zoubek

Boston Children's Hospital

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Christina Peters

Boston Children's Hospital

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Peter F. Ambros

Community College of Rhode Island

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Heinrich Kovar

Medical University of Vienna

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Ulrike Pötschger

Medical University of Vienna

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Gerhard Fritsch

Boston Children's Hospital

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Michael Dworzak

Medical University of Vienna

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Ruth Ladenstein

Boston Children's Hospital

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