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JOURNAL ARTICLE
REVIEW
Evolution and optimization of therapies for acute lymphoblastic leukemia in infants.
International Journal of Hematology 2022 November 29
Acute lymphoblastic leukemia (ALL) in infants accounts for less than 5% of pediatric ALL and is biologically and clinically unique. Approximately 70% to 80% of cases present as an aggressive leukemia with KMT2A gene rearrangement (KMT2A-r), which is one of the most difficult-to-cure forms of pediatric leukemia. Owing to continuing global efforts through multicenter clinical trials since the mid-1990s, a standard of care for infant KMT2A-r ALL, including minimal residual disease-based risk stratifications, "hybrid chemotherapy" incorporating myeloid leukemia-like drugs (e.g., cytarabine) into the ALL chemotherapy backbone, and selective use of allogeneic hematopoietic stem cell transplantation, has now been established. However, there are still many concerns regarding treatment of infants with KMT2A-r ALL, including insufficient efficacy of the current standard therapies, limited pharmacokinetic/pharmacodynamic data on drugs in infants, and management of both acute and late toxicities. Refinements in risk stratification based on leukemia biology, as well as the introduction of emerging novel immunotherapies and molecular-targeted drugs to contemporary therapy, through international collaboration would provide key solutions for further improvement in outcomes.
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