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.
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.
Schrappe
M
M
Department of Pediatric Hematology and Oncology, Medizinische Hochschule Hannover, Federal Republic of Germany (FRG). schrappe.martin@mh-hannover.de
Reiter
A
A
Ludwig
W D
WD
Harbott
J
J
Zimmermann
M
M
Hiddemann
W
W
Niemeyer
C
C
Henze
G
G
Feldges
A
A
Zintl
F
F
Kornhuber
B
B
Ritter
J
J
Welte
K
K
Gadner
H
H
Riehm
H
H
D000293:Adolescent; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage; D001932:Brain Neoplasms / Q000517:prevention & control; D002648:Child; D002675:Child, Preschool; D016371:Cranial Irradiation; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000532:radiotherapy; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000532:radiotherapy; D011379:Prognosis; D012044:Regression Analysis; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
D000903:Antibiotics, Antineoplastic; D001215:Asparaginase