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Blood, 1 May 2008, Vol. 111, No. 9, pp. 4477-4489. Prepublished online as a Blood First Edition Paper on February 19, 2008; DOI 10.1182/blood-2007-09-112920.
CLINICAL TRIALS AND OBSERVATIONS 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 951 Department of Pediatrics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany; 2 Pediatric Hematology and Oncology, Justus-Liebig University, Gieβen, Germany; 3 Division of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany; 4 St Anna Kinderspital, Vienna, Austria; 5 Division of Pediatric Pulmonology and Neonatology, Hannover Medical School, Hannover, Germany; 6 Department of Pediatrics, Klinikum Oldenburg, Oldenburg, Germany; 7 Pediatric Hematology/Oncology, University Children's Hospital, Homburg/Saar, Germany; 8 Hematology/Oncology, Robert-Rössle-Klinik at the HELIOS Klinikum, Charité, Berlin, Germany; 9 Pediatric Hematology/Oncology, University Children's Hospital, Münster, Germany; 10 Department of Pediatric Oncology, University Children's Hospital, Zürich, Switzerland; 11 Pediatric Hematology/Oncology, Ostschweizer Kinderspital, St Gallen, Switzerland; 12 Pediatric Hematology and Oncology, Charité Medical Center, Humboldt University, Berlin, Germany; 13 Department of Pediatric Oncology, University Hospital, Erlangen, Germany; 14 Pediatric Hematology and Oncology, University Hospital, Frankfurt, Germany; 15 Division of Pediatric Hematology and Oncology, University of Freiburg, Freiburg, Germany; 16 Department of Pediatric Hematology and Oncology, University Hospital, Jena, Germany; 17 Division of Pediatric Hematology and Oncology, University Hospital, Bonn, Germany; 18 Division of Pediatric Hematology and Oncology, Medical University Graz, Graz, Austria; 19 Department of Pediatrics, Municipal Hospital, Kassel, Germany; and 20 Department of Pediatric Hematology and Oncology, University Hospital, Tübingen, Germany 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.
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