OBJECTIVES: Pediatric ALL is the most common childhood leukemia, with 20% of children experiencing relapse after initial complete response (CR) to first-line treatment. A systematic literature review (SLR) and meta-analysis (MA) were conducted to determine the effects of treatments for pediatric r/r ALL. METHODS: EMBASE, MEDLINE, and CENTRAL databases were searched from 01/01/2000-12/31/2016 using keywords for pediatric r/r ALL paired with terms for relevant treatments to identify studies reporting efficacy and safety data. Proceedings from recent oncology conferences were also searched. Statistical analysis was limited to studies with comparable populations and treatments. Random-effects MA of single-arm data were performed to determine 6- and 12-month OS rates, median OS, and CR rate (timepoint not reported) for pediatric r/r ALL patients treated with clofarabine + cyclophosphamide + etoposide (CCE). RESULTS: Studies included in the SLR were heterogeneous, only five of the 46 studies identified were sufficiently comparable for MA in terms of outcomes and populations (median age 8-14 years, median 2 prior lines of therapy). All five were single-arm studies in primarily B-cell immunophenotype evaluating CCE, a treatment with pooled 6-month OS of 43.5% (95% CI: 32.6%–55.1%), 1-year OS of 26.7% (95% CI: 17.5%–38.3%), and median OS of 5.2 (95% CI: 3.2–8.6) months. The CR rate was 43.2% (33.7%–53.3%) across the five studies (timepoint not reported). CONCLUSIONS: This is the first SLR and MA to be conducted on treatment of pediatric r/r ALL and evidence was heterogeneous. MA were only possible for single-arm trials examining CCE. Pediatric r/r ALL patients treated with CCE had poor survival, with a low 1-year OS rate of less than 30% and short OS duration (median 5.2 months). Lack of data on timepoint of assessment make the CR rate results difficult to interpret. New treatments are needed to better manage pediatric r/r ALL.