Global Disparities in ALL Treatment and Outcome

Despite being curable and concerted outreach efforts, in global survival of childhood ALL, a large gap remains. This large survival gap globally can be addressed because curing ALL is cost-effective. Specifically, effective chemotherapy drugs used in ALL treatment are affordable and generic, and treatment can be given outpatient. Indeed, for every dollar invested, survivors of ALL will return more than three dollars economically. ALL is a heterogeneous disease. Because of its genetic heterogeneity, ALL is best treated in two or three strata based on the risk of relapse. An effective, widely available risk factor is the NCI criteria, comprising of age and WBC at presentation. To cure the curable, low- and middle-income countries (LMICs) should start with treating NCI standard risk ALL among urban children. Induction therapy should be less intensive. Anthracycline is myelosuppressive and should be omitted in induction. Omitting anthracycline makes induction is less toxic and consumes less supportive care like antibiotics and blood products. This reduces abandonment and financial hardship. Recently, adding blinatumomab, an anti-CD19 T-cell engager, has been shown to improve outcomes in B-ALL patients, without significant myelosuppression and manageable toxicities. Curing the curable allows LMIC to achieve initial small successes and scale up their health systems. Genetic variations between races also contribute to global disparities in treatment outcomes. Asian children with ALL have higher proportions of DUX4 and ZNF-384 fusions; African Americans have higher proportion of T-ALL and TCF3-PBX1. In addition, racial differences may account for different drug efficacy or toxicity. For example, testing for known variants in NUDT15 in Asians and TPMT in Caucasians can help improve dosing of mercaptopurine. Taken together, reducing global disparities in treatment outcome of childhood ALL should start with curing the curable and scaling up the health system to cope with the extra care needed.