Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

BACKGROUND: The effects on long-term outcome in childhood acute lymphoblastic leukaemia (ALL) of the duration and the intensity of maintenance chemotherapy need to be assessed reliably. With this objective the Childhood ALL Collaborative Group coordinated a worldwide overview of all randomised trials that began before 1987. METHODS: Individual patient data were sought for about 3900 children in trials of longer vs shorter maintenance (eg, 3 vs 2 years), 3700 in trials of intensive "reinduction" chemotherapy during maintenance, and 4400 in trials of various 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. FINDINGS: Deaths during remission were increased by longer maintenance (2.7 percent vs 1.2 percent), VP pulses (4.0 vs 3.2 percent), and intensive reinduction (4.8 percent vs 3.3 percent), but these increases were counterbalanced by reductions in relapses. Total events (relapse or death) were significantly reduced by longer maintenance (23.3 percent vs 27.6 percent), VP pulses (31.2 percent vs 40.4 percent) and intensive reinduction (27.8 percent vs 35.8 percent) (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 percent vs 22.3 percent; 2p=0.01). INTERPRETATION: Intensive reinduction chemotherapy in these trials produced an absolute improvement of about 4 percent in long-term survival; if the extra deaths in remission had been avoided, this would have been a 5 percent benefit. Further improvements in survival seem more likely to be obtained with intensive treatment than with longer low-level maintenance.

Original publication




Journal article



Publication Date





1783 - 1788


Adolescent, Adult, Antineoplastic Agents, Child, Dose-Response Relationship, Drug, Drug Administration Schedule, Humans, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Randomized Controlled Trials as Topic, Survival Analysis