Background: 6-Mercaptopurine is a cornerstone of maintenance therapy for pediatric ALL. Response to 6MP is typically determined by the ANC. Therapeutic ANC range while receiving 6MP is between 500-1,500/µL. In addition to desired myelosuppression, 6MP is associated with multiple adverse drug effects. Increased doses of 6MP can lead to therapeutic ANC values; however, patients may experience adverse effects before obtaining therapeutic myelosuppression, often deemed “skewed metabolism.” Allopurinol may potentially correct skewed 6MP metabolism. Procedure: Pediatric patients with ALL with 6MMP and 6TGN metabolites drawn during maintenance therapy were analyzed for allopurinol use. The primary outcome evaluated the percentage of time spent in therapeutic ANC range before and after allopurinol initiation. Additionally, the difference in 6MMP:6TGN ratios before and after allopurinol initiation, incidence of hepatotoxicity, and rates of relapse, were analyzed. Results: Ninety-five patients were included for analysis. Thirty-two (34%) patients received allopurinol. There were no significant differences in baseline demographics between the patients who received allopurinol and those who did not. When comparing ANC values pre- and post- allopurinol initiation, a statistically significant increase in the percentage of time spent in therapeutic range was observed (27% vs. 43%; P=0.03). Additionally, when comparing metabolite ratios pre- and post-allopurinol initiation, a statistically significant decrease in 6MMP:6TGN metabolite ratio values was observed (86.7 vs 3.6; P < 0.0001). Conclusions: Allopurinol significantly increased the percent time in therapeutic ANC range and can be safely utilized to significantly lower the ratio of 6MMP:6TGN metabolites, alleviating the undesirable side effects of 6MMP, and optimizing the anti-leukemic effects associated with 6TGN.

Rearrangements of the KMT2A gene are characteristic of infantile acute lymphoblastic leukemia (ALL) and are associated with increased lineage plasticity and resistance to therapy. Here, we describe the case of a 9-month-old infant with infantile ALL who experienced multiple immunophenotypic switches in her leukemia throughout therapy and ultimately achieved remission with the combination of CPX-351 and Inotuzumab. This case highlights the unique clinical challenges infantile ALL poses on monitoring therapeutic response with current methods of measuring minimal residual disease as well as the challenges in treating infantile B-ALL.

Population-level estimates of the survival of children from low- and middle-income countries diagnosed with solid tumors do not currently exist, in contrast to outcomes of hematologic and central nervous system cancers, which have been collated from population-based cancer registries and published by the CONCORD Programme. To fill this knowledge gap, we conducted a systematic review of PubMed Legacy, Embase, Web of Science, Cochrane Central Registry of Controlled Trials, and three regional databases for publications that reported survival of children diagnosed age 0-14 years with any malignancy from January 2011 to December 2016. The search identified 4695 original records; 51 articles met inclusion criteria. The range of survival reported was broad; for instance, 5-year overall survival for retinoblastoma ranged from 48% in Central America to 98% in China. However, the paucity of published statistics prevented approaches for meta-analyses and emphasizes the need for more standardized data collection and reporting.