Improved outcome in childhood acute lymphoblastic leukemia despite reduceduse of anthracyclines and cranial radiotherapy: results of trial ALL-BFM 90

Trial ALL-BFM 90 was designed to improve outcome in patients with childhood acute lymphoblastic leukemia (ALL) by using a reduced treatment regimen. p atients were stratified into a standard-risk group (SRG), a medium-risk gro up (MRG), both defined by adequate early treatment response; and a high-ris k group (HRG), defined by inadequate response to the cytoreductive predniso ne prephase, induction failure, or Philadelphia-chromosome-positive ALL. Fo ur treatment modifications were evaluated: dose intensification in inductio n by a more rapid drug sequence; administration of L-asparaginase during co nsolidation therapy in the MRG (randomized); enforced consolidation by rota tional 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 (less than or equal to 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, i n which EFS was 47% +/- 5% (P =.04), The rates of isolated central nervous system relapse in the MRG and HRG were 0.8% end 1.6%, respectively; thus, t he 12-Gy preventive cranial radiotherapy regimen apparently provided suffic ient central nervous system prophylaxis. The overall improvement over the r esults in ALL-BFM 86 (6-year EFS, 72%; P=.001)was based on fewer recurrence s among patients in the MRG with B-cell-precursor ALL, indicating an advant age of more condensed induction therapy. In multivariate analysis, inadequa te in vivo response emerged as the strongest adverse prognostic variable, ( Blood, 2000; 95:3310-3322) (C) 2000 by The American Society of Hematology.