Hematopoietic Cell Transplantation in High-Risk Childhood Acute Myelogenous Leukemia

Abstract

In this issue of Biology of Blood and Marrow Transplantation, Burke et al. present their findings on the efficacy of allogeneic hematopoietic stem cell transplantation (HCT) in patients with high-risk childhood acute myelogenous leukemia (AML). This limited single-institution study demonstrates that patients with high-risk disease (as defined by cytogenetics/molecular markers) who received allogeneic HCT in first compete remission (CR) have a favorable outcome, similar to those with standard-risk disease. The role of HCT as consolidation therapy for childhood AML has evolved significantly since Woods et al. first demonstrated that children who received allogeneic HCT from related donors had an improved outcome compared with chemotherapy recipients [1]. This study further demonstrated that pretransplantation chemotherapy can affect posttransplantation survival; patients who received more intensive induction chemotherapy had a significantly lower rate of relapse and more favorable survival after HCT, suggesting that quality of remission (lower residual disease) was an important determinant of post-HCT survival. In this study, although HCT carried higher treatment-related mortality, lower relapse resulted in more favorable outcomes in HCT recipients. This seminal study led to the change in the standard of care in childhood AML in the United States, where patients with newly diagnosed AML with suitably matched related donors were allocated to receive HCT in first CR. Subsequent studies (Children’s Cancer Group 2961 and Children’s Oncology Group 03P1 pediatric AML trials) allocated all patients with a matched family donor to receive HCT in first CR [2,3]. With the improvements in HLA typing and supportive care, and with broader availability of suitable donors, unrelated HCT has been more broadly used in patients in first CR. Further, reevaluation of the role of stem cell transplantation in AML in the context of emerging prognostic factors has changed the utility of HCT from a biologic allocation based on donor availability to a more risk-appropriate therapeutic allocation aimed at improving outcome while minimizing risk and toxicity. In this risk-based allocation to HCT, patients with