Abstract
Although childhood acute lymphoblastic leukemia (ALL) is curable, global disparities in treatment outcomes remain. To reduce these global disparities in low-middle income countries (LMIC), a paradigm shift is needed: start with curing low-risk ALL. Low-risk ALL, which accounts for >50% of patients, can be cured with low-toxicity therapies already defined by collaborative studies. We reviewed the components of these low-toxicity regimens in recent clinical trials for low-risk ALL and suggest how they can be adopted in LMIC. In treating childhood ALL, the key is risk stratification, which can be resource stratified. NCI standard-risk criteria (age 1–10 years, WBC < 50,000/uL) is simple yet highly effective. Other favorable features such as ETV6-RUNX1, hyperdiploidy, early peripheral blood and bone marrow responses, and simplified flow MRD at the end of induction can be added depending on resources. With limited supportive care in LMIC, more critical than relapse is treatment-related morbidity and mortality. Less intensive induction allows early marrow recovery, reducing the need for intensive supportive care. Other key elements in low-toxicity protocol designs include: induction steroid type; high-dose versus low-dose escalating methotrexate; judicious use of anthracyclines; and steroid pulses during maintenance. In summary, the first effective step in curing ALL in LMIC is to focus on curing low-risk ALL with less intensive therapy and less toxicity.
Highlights
Childhood acute lymphoblastic leukemia (ALL) is curable
To be able to define this lowest-risk subgroup, there is a requirement for excellent cytogenetics or FISH setup defined hyperdiploidy, oncogene fusion screening for ETV6-RUNX1, and EOI minimal residual disease (MRD)
While of interest to low-middle income countries (LMIC) or Low-Income Countries (LIC) groups with limited access to serum MTX drug monitoring, the excellent outcomes achieved in these studies were derived from high-income countries (HIC) settings with individual protocol-specific caveats such as the more stringent criteria imposed by the Children’s Oncology Group (COG) to be considered as low risk, and later intensification in other parts of the protocol in the UKALL 2003, which have been reported to be toxic even in HIC settings
Summary
Childhood acute lymphoblastic leukemia (ALL) is curable. Underpinning the cure for ALL is more than half a century of intensive collaborative research [1] that has systematically tested and defined highly effective drug combinations which form the backbone of contemporary protocols. The high cure rates of ALL achieved in HIC are not seen in low-middle income countries (LMIC) [3]. With 80% of the world childhood ALL burden residing in LMIC [4,5], our success in curing childhood ALL remains limited and geographically restricted [2]. To reduce such glaring disparities, many groups such as the International Pediatric Oncology Society (SIOP), VIVA Foundation for Childhood Cancer, St Jude Global, and the World Health Organization are beginning to tackle the obstacles to widespread adoption of effective treatment. We focus on key components of contemporary trials on curing low-risk ALL, cost-effectively
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