The hallmarks of hematopoietic stem cell transplantation for pediatric acute myeloid leukemia

Allogeneic hematopoietic stem cell transplantation (HSCT) has significantly improved the outcome of children with high-risk (HR) acute myeloid leukemia (AML). Implementing allogeneic HSCT depends on numerous factors, including adverse cytogenetics, molecular abnormalities, poor response to first-line treatment, or relapsed or primary refractory disease. In HR AML, allogeneic HSCT is considered to be the consolidation strategy of choice in first complete remission (CR1) and offers the best chance of cure for patients with relapsed disease. Advances in donor/recipient typing, conditioning regimens, graft-versus-host-disease (GvHD) management, and supportive care have contributed to this improvement in overall—and transplant—outcome. This review will comprehensively discuss indications for HSCT and its modalities in pediatric AML by examining past, current, and future strategies for disease- and response-related stratification. We will examine the key importance of low/negative measurable residual disease (MRD) before transplantation and discuss conditioning regimens and graft variables, as well as novel approaches to harness the graft-versus-leukemia (GvL) effect, including targeted immunotherapy. The review will also address toxicities associated with HSCT, GvHD prophylaxis, and the management of treatment failure. Ultimately, this review seeks to inform clinical practice and highlights how improved outcomes have been achieved through the collective efforts of international study groups.