Results and conclusions of the European Intergroup EURO-LB02 trial in children and adolescents with lymphoblastic lymphoma
Eva Landmann,
Birgit Burkhardt,
Martin Zimmermann,
Ulrike Meyer,
Wilhelm Woessmann,
Wolfram Klapper,
Grazyna Wrobel,
Angelo Rosolen,
Marta Pillon,
Gabriele Escherich,
Andishe Attarbaschi,
Auke Beishuizen,
Karin Mellgren,
Robert Wynn,
Richard Ratei,
Adriana Plesa,
Martin Schrappe,
Alfred Reiter,
Christophe Bergeron,
Catherine Patte,
Yves Bertrand
Affiliations
Eva Landmann
Department of Pediatric Hematology and Oncology, Justus-Liebig-University, Giessen, Germany
Birgit Burkhardt
Department of Pediatric Hematology and Oncology, Children’s University Hospital, Münster, Germany
Martin Zimmermann
Department of Pediatric Hematology and Oncology, Hannover Medical School, Germany
Ulrike Meyer
Department of Pediatric Hematology and Oncology, Justus-Liebig-University, Giessen, Germany
Wilhelm Woessmann
Department of Pediatric Hematology and Oncology, Justus-Liebig-University, Giessen, Germany
Wolfram Klapper
Department of Hematopathology and Lymph Node Registry, University Hospital, Kiel, Germany
Grazyna Wrobel
Department of Bone Marrow Transplantation, Children’s Oncology and Hematology, Wroclaw Medical University, Poland
Angelo Rosolen
Clinica di Oncoematologia Pediatrica, Università di Padova, Italy
Marta Pillon
Clinica di Oncoematologia Pediatrica, Università di Padova, Italy
Gabriele Escherich
Clinic for Pediatric Hematology and Oncology, University Medical Center, Hamburg, Germany
Andishe Attarbaschi
Department of Pediatric Hematology and Oncology, St. Anna Children’s Hospital, Medical University of Vienna, Austria
Auke Beishuizen
Department of Pediatric Hematology/Oncology, Erasmus MC - Sophia Children’s Hospital, Rotterdam, the Netherlands and the Dutch Childhood Oncology Group, the Hague, the Netherlands
Karin Mellgren
Department of Pediatric Oncology and Hematology, The Queen Silvia Children’s Hospital, Göteborg, Sweden
Robert Wynn
Central Manchester University Hospitals, Great Britain
Richard Ratei
Department of Hematology, Oncology and Tumor Immunology, Helios Klinikum, Berlin-Buch, Germany
Adriana Plesa
Department of Hematopathology and Flow Cytometry, CHU, Lyon-HCL, France
Martin Schrappe
Department of Pediatrics, Christian-Albrechts-University, Kiel, Germany
Alfred Reiter
Department of Pediatric Hematology and Oncology, Justus-Liebig-University, Giessen, Germany
Christophe Bergeron
Institut d’Hematologie et d’Oncologie Pediatrique, Centre Léon Bérard and HCL, Claude Bernard University, Lyon, France
Catherine Patte
Department of Gustave Roussy, Villejuif, France
Yves Bertrand
Institut d’Hematologie et d’Oncologie Pediatrique, Centre Léon Bérard and HCL, Claude Bernard University, Lyon, France
In the European Intergroup EURO-LB02 trial, children and adolescents with lymphoblastic lymphoma underwent the non-Hodgkin lymphoma Berlin-Frankfurt-Münster protocol without prophylactic cranial radiotherapy. The primary aims of this trial were to test whether replacing prednisone with dexamethasone during induction increases event-free survival in the subgroups with T-cell lymphoblastic lymphoma and whether therapy duration could be reduced from 24 to 18 months (factorial design, randomizations). These questions could not be answered due to premature closure of the trial. Here we report on the secondary aims of the trial: whether the results of the NHL-BFM90 study could be reproduced and evaluation of disease features and prognostic factors. Three hundred and nineteen patients (66 with precursor B-cell lymphoblastic lymphoma, 233 with T-cell lymphoblastic lymphoma, 12 with mixed phenotype, 8 not classifiable) were enrolled. In induction, 215 patients received prednisone and 104 patients received dexamethasone. The median follow-up was 6.8 years (range, 3.0–10.3). The 5-year event-free survival was 82±2% [12 toxic deaths, 5 secondary malignancies, 43 non-response/relapse (central nervous system n=9; all received prednisone during induction)]. The event-free survival rate was 80±5% for patients with precursor B-cell lymphoblastic lymphoma, 82±3% for those with T-cell lymphoblastic lymphoma, and 100% for patients with a mixed phenotype. During induction, significantly more grade III/IV toxicities were observed in patients receiving dexamethasone, resulting in significant treatment delays. The number of toxic deaths did not differ significantly. The only variable associated with outcome was performance status at diagnosis. The 90% event-free survival rate for patients with T-cell lymphoblastic lymphoma shown in study NHL-BFM90 was not replicated, mainly due to more toxic deaths and central nervous system relapses. Dexamethasone in induction may prevent central nervous system relapse more effectively than prednisone but produces a higher burden of toxicity. (#NCT00275106).