Improved outcome in childhood acute lymphoblastic leukemia despite reduced use of anthracyclines and cranial radiotherapy: results of trial ALL-BFM 90. German-Austrian-Swiss ALL-BFM Study Group

Item Type:	Article
Title:	Improved outcome in childhood acute lymphoblastic leukemia despite reduced use of anthracyclines and cranial radiotherapy: results of trial ALL-BFM 90. German-Austrian-Swiss ALL-BFM Study Group
Creators Name:	Schrappe, M. and Reiter, A. and Ludwig, W.D. and Harbott, J. and Zimmermann, M. and Hiddemann, W. and Niemeyer, C. and Henze, G. and Feldges, A. and Zintl, F. and Kornhuber, B. and Ritter, J. and Welte, K. and Gadner, H. and Riehm, H.
Abstract:	Trial ALL-BFM 90 was designed to improve outcome in patients with childhood acute lymphoblastic leukemia (ALL) by using a reduced treatment regimen. Patients were stratified into a standard-risk group (SRG), a medium-risk group (MRG), both defined by adequate early treatment response; and a high-risk group (HRG), defined by inadequate response to the cytoreductive prednisone prephase, induction failure, or Philadelphia-chromosome-positive ALL. Four treatment modifications were evaluated: dose intensification in induction by a more rapid drug sequence; administration of L-asparaginase during consolidation therapy in the MRG (randomized); enforced consolidation by rotational elements in the HRG; and reduction in the dose of anthracyclines and use of only 12-Gy preventive cranial radiotherapy in the MRG and HRG, with the aim of avoiding toxicity. Among all 2178 patients (</= 18 years of age), the 6-year event-free survival (EFS) rate (+/- SE) was 78% +/- 1%, with a median observation time of 4.8 years. EFS was 85% +/- 2% in the SRG (n = 636) and 82% +/- 1% in the MRG (n = 1299). L-asparaginase did not improve outcome in the MRG: the event-free interval was 83% +/- 2% with L-asparaginase (n = 528) and 81% +/- 2% without it (n = 557). Because there were more systemic relapses in the HRG (n = 243), EFS was 34% +/- 3%, an outcome inferior to that in the HRG in a previous trial, ALL-BFM 86, in which EFS was 47% +/- 5% (P =.04). The rates of isolated central nervous system relapse in the MRG and HRG were 0.8% and 1.6%, respectively; thus, the 12-Gy preventive cranial radiotherapy regimen apparently provided sufficient central nervous system prophylaxis. The overall improvement over the results in ALL-BFM 86 (6-year EFS, 72%; P =. 001) was based on fewer recurrences among patients in the MRG with B-cell-precursor ALL, indicating an advantage of more condensed induction therapy. In multivariate analysis, inadequate in vivo response emerged as the strongest adverse prognostic variable.
Keywords:	Antineoplastic Antibiotics, Antineoplastic Combined Chemotherapy Protocols, Asparaginase, Brain Neoplasms, Cranial Irradiation, Disease-Free Survival, Immunophenotyping, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Prognosis, Regression Analysis, Survival Analysis, Time Factors, Treatment Outcome
Source:	Blood
ISSN:	0006-4971
Publisher:	American Society of Hematology
Volume:	95
Number:	11
Page Range:	3310-3322
Date:	1 June 2000
Official Publication:	http://bloodjournal.hematologylibrary.org/cgi/content/abstract/95/11/3310
PubMed:	View item in PubMed

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