The evolution of allogeneic stem cell transplant for children and adolescents with acute myeloid leukemia

Survival rates in subsets of pediatric patients who have acute myeloid leukemia (AML) with favorable risk features are now greater than 90%. However, outcomes for patients with high-risk (HR) features remain unacceptably poor. As novel technologies for the identification of HR biomarkers and the detection of residual disease are developed, risk stratification and the application of allogeneic hematopoietic stem cell transplant (HSCT) are evolving. HSCT has been shown to benefit subpopulations of pediatric patients with AML, including those with HR cytogenetic translocations, genetic mutations, and/or residual disease after induction. Targeted therapies have shown promise for improving outcomes, and their integration into standard therapy and HSCT regimens is a critical area of interest. Also, expansion of the donor pool has led to the successful use of alternative donor sources for those patients without a matched sibling. However, transplant-related morbidity and mortality and late effects are major limiting factors. Reduced-intensity conditioning regimens have resulted in outcomes equivalent to those achieved with myeloablative regimens among patients in complete remission. The limitation of transplant-related morbidity and mortality through reduced-intensity conditioning and supportive care, and improved survival through optimal alloreactivity in combination with targeted therapy, are steps toward advancing outcomes for pediatric patients who have AML with HR features.