Sumit Gupta

The benefit associated with the incorporation of vincristine-corticosteroid pulses into maintenance therapy for pediatric acute lymphoblastic leukemia (ALL) is unclear, particularly in the context of modern intensive therapy. This systematic review and meta-analysis examined the impact of reducing frequency of vincristine-steroid pulses during maintenance for newly diagnosed pediatric patients with B-cell ALL. Two authors reviewed all eligible studies identified through a comprehensive search, extracted data from the 25 included publications (12 513 patients), and assessed risk of bias. We created historical and contemporary subgroups; the latter included trials providing a version of Protocol III from early Berlin-Frankfurt-Munster trials and eliminating routine prophylactic cranial radiation. Meta-analysis of event-free survival data suggested no benefit between more frequent or less frequent pulses in contemporary trials (HR 0.96, 95%CI 0.85-1.09) which differs significantly from historical trials (HR 0.79, 95%CI 0.68-0.91, p=0.04). We found no significant impact of reduced pulse frequency on overall survival or relapse risk. There was however an increased odds of Grade 3+ non-hepatic toxicity in the high pulse frequency group (OR 1.31, 95%CI 1.12-1.52). This systematic review suggests that the previous benefit conferred by frequent pulses of vincristine-steroids in maintenance therapy for pediatric B-cell ALL in historical trials no longer applies in contemporary trials but is associated with toxicity. These results will help guide development of the next phase of clinical trials in the field of pediatric ALL and question the continued use of pulses in maintenance for patients not on clinical trials, particularly those experiencing toxicity.