Intensive treatment of children with acute lymphoblastic leukemia according to ALL-BFM-86 without cranial radiotherapy: Results of Dutch Childhood Leukemia Study Group protocol ALL-7 (1988-1991)

In The Netherlands from July 1988 to October 1991, children (0 to 16 years of age) with de novo acute lymphoblastic leukemia (ALL) were treated accord ing to protocol ALL-7 of the Dutch Childhood Leukemia Study Group (DCLSG). In this protocol, chemotherapy and treatment stratification were identical to the ALL-BFM-86 protocol (Reiter et at, Blood 84:3122, 1994), but cranial irradiation was restricted to patients with initial central nervous system (CNS) involvement. Patients were stratified into 3 risk groups, based on l eukemia cell mass and response to initial treatment: standard-risk group (S RG), risk group (RG), and experimental group (EG). As in ALL-BFM-86, a rand omized study on late intensification (protocol S) was performed in RG patie nts, and during the study (since October 1990), early reinduction treatment (protocol II) was introduced for SRG patients. Treatment duration for all patients was 18 months. Two hundred eighteen children entered the study: 74 SRG, 127 RG, and 17 EG patients. The overall complete remission (CR) rate was 98%. The 5-year event-free survival (EFS) for all DCLSG ALL-7 patients was 65.3% (standard error [SE] 3.2%), which was significantly different fro m the 73% (SE 1%) 8-year EFS achieved in the ALL-BFM-86 study (P = .02, Z-t est). However, restricting the analysis to SRG patients receiving protocol II with a total duration of treatment of 18 months, the 5-year EFS rates we re 64.6% (SE 4.0%) and 67% (SE 4%), respectively, and no significant differ ence could be established (P = .67, Z-test). The 5-year EFS rates for SRG, RG, and EG patients were 63.5% (SE 5.6%), 66.6% (SE 4.2%), and 63.3% (SE 12 .0%), respectively. SRG patients receiving protocol II fared better than pa tients not receiving protocol II (5-year EFS 76.7% [SE 7.7] and 54.5% [SE 7 .5], respectively). No difference in 8-year EFS was observed in RG patients randomized to receive or not to receive late intensification with protocol S. The overall CNS relapse rate at 5 years was 5.5%. The incidence rate at 5 years was 11.4% in SRG patients not receiving protocol II, whereas no CN S relapses occurred in SRG patients receiving protocol II. Six children die d in first complete remission and 2 children developed a second malignancy (thyroid carcinoma and acute nonlymphoblastic leukemia). Systemic high-dose methotrexate (MTX) and intrathecal chemotherapy is a safe and effective me thod of CNS prophylaxis in the context of BFM-oriented treatment for all ch ildren with ALL, regardless of the risk group (with the possible exception of T-ALL patients with high white blood cell counts). The results of the DC LSG ALL-7 study confirm those of the ALL-BFM-86 study showing that early re induction with protocol II is essential in the treatment of SRG patients an d that late intensification with protocol S does not improve the prognosis for RG patients. (C) 1999 by The American Society of Hematology.