Results in 258 children with acute lymphoblastic leukemia (ALL) treated in the Czech Republic between 1979 and 1983 according to in-house protocols demonstrated a dismal outcome. The complete remission (CR) rate was 82%, 3-year event free survival (EFS) 30% and overall survival 44%. The Czech Working Group for Pediatric Hematology was established in 1985 and in 1986, treatment of children with ALL was unified on a national basis using the ALL-BFM 83 protocol. Between 1986 and 1990, a total of 339 children were treated in 10 regional centers. CR increased to 90.5% and the 5-year EFS almost doubled the previous 3-year rate to 58% (SE 2%) [1]. A new ALL-BFM 90 protocol was started in 1990 and continued until 1996. Our results of this wellestablished treatment in the first years of the postcommunist era of the Czech Republic are presented in this report.
Children and adolescents 0-18 years of age diagnosed with ALL from June 1990 through May 1996 at one of the 10 regional centers were eligible for the study. Immunophenotyping and karyotyping of leukemic cells was performed by laboratories at the university hospitals. Since June 1993 RT-PCR based prospective screening for BCR/ABL rearrangement was investigated in 106 children and MLL/AF4 fusion gene in 45 consecutive children since March 1995.
The design and treatment regimens of protocol ALL-BFM 90 has been published elsewhere [2]. The only modification made in our study in comparison with the original protocol was the composition of protocol M. The consolidation treatment for Standard Risk Group (SRG) and Medium Risk Group (MRG) (Protocol M) consisted of 8-week course of mercaptopurine and intermediate (1g/m 2 /36 hr) or high dose (5g/m 2 /24 hr) dose methotrexate (MTX). Only one center used high dose (HD) MTX from the beginning of the study; other centers changed from intermediate dose (ID) to HD gradually depending on the ability of each center to determine the MTX blood level. Two small centers continued with ID MTX through the whole study. Leucovorin rescue for ID MTX consisted of 15 mg/m 2 intravenously (IV) given 48 and 54 hr from the start of MTX infusion. For HD MTX the leucovorin rescue was scheduled according to the original protocol [2].
The MTX dose effect was analyzed using the eventfree interval (EFI) calculated from the beginning of protocol M to the first event, if any; (i.e., relapse, death in CCR, second malignancy) or to the time of analysis.