DURATION AND INTENSITY OF MAINTENANCE CHEMOTHERAPY IN ACUTE LYMPHOBLASTIC-LEUKEMIA - OVERVIEW OF 42 TRIALS INVOLVING 12,000 RANDOMIZED CHILDREN

Background The effects on long-term outcome in childhood acute lymphob lastic leukaemia (ALL) of the duration and the intensity of maintenanc e chemotherapy need to be assessed reliably. With this objective the C hildhood ALL Collaborative Group coordinated a worldwide overview of a ll randomised trials that began before 1987. Methods. Individual patie nt data were sought for about 3900 children in trials of longer vs sho rter maintenance leg, 3 vs 2 years), 3700 in trials of intensive ''rei nduction'' chemotherapy during maintenance, and 4400 in trials of vari ous other questions, including 1300 in trials of pulses of vincristine and prednisone (VP) during maintenance. Analyses were of survival in first remission, overall survival, and cause-specific mortality. Findi ngs Deaths during remission were increased by longer maintenance (2.7% vs 1.2%), VP pulses (4.0 vs 3.2%), and intensive reinduction (4.8% vs 3.3%), but these increases were counterbalanced by reductions in rela pses. Total events (relapse or death) were significantly reduced by lo nger maintenance (23.3% vs 27.6%), VP pulses (31.2% vs 40.4%) and inte nsive reinduction (27.8% vs 35.8%) (each 2p<0.001). Many of those who relapsed were successfully re-treated, however, and only for intensive reinduction was overall survival significantly improved (18.5% vs 22. 3%; 2p=0.01). Interpretation Intensive reinduction chemotherapy in the se trials produced an absolute improvement of about 4% in long-term su rvival; if the extra deaths in remission had been avoided, this would have been a 5% benefit. Further improvements in survival seem more lik ely to be obtained with intensive treatment than with longer low-level maintenance.