Long-term results of three randomized trials (58831,58832,58881) in childhood acute lymphoblastic leukemia: a CLCG-EORTC report

We present here the long-term results of three randomized clinical trials c onducted on children with newly diagnosed acute lymphoblastic leukemia (ALL ) between 1983 and 1998 by the Children Leukemia Cooperative Group (CLCG) f rom EORTC. In study 58831/32, the overall event-free survival (EFS) rates ( +/- s.e.) at 6 and 10 years were 66% +/-1.8% and 65% +/-1.8%, respectively, and the risk of isolated central nervous system (CNS) relapse was 6%+/-1% and 7%+/-1%, respectively. In patients with a standard risk of relapse the omission of cyclophosphamide had no adverse effect on disease-free survival rates at 10 years (trial 58831). In medium- and high-risk patients the omi ssion of radiotherapy did not increase the risk of CNS or systemic relapse (trial 58832). In study 58881 (1989-1998) the overall EFS rate at 8 years w as 68.4% +/- 1.2% and the risk of isolated CNS relapse was 4.2% +/- 0.5%. I n this trial which adressed three randomized questions, the following resul ts were obtained: the combination of cytarabine at high doses with methotre xate at high doses during interval therapy did not improve prognosis. The a ddition of g-mercaptopurine iv during maintenance increased the risk of lat e relapse. E. coli asparaginase was more toxic and has a higher efficacy th an Erwinia asparaginase. Leukocyte counts >100 x 10(9)/1, specific genetic abnormalities, a poor initial response to steroids or a high level of minim al residual disease at early time points were consistently associated with an adverse prognosis in the 58881 trial.