Future of Allogeneic Hematopoietic Stem Cell Transplantation for Chemotherapy-Resistant Pediatric Acute Leukemia: Potential Advances

Abstract

Fred Hutchinson Cancer Research Center, Seattle, WA, USA University of Washington Department of Pediatrics, Seattle, WA, USA Ben Towne Center for Childhood Cancer Research, Seattle Children’s Research Institute, Seattle, WA, USA *Author for correspondence: Tel.: +1 206 667 6572; Fax: +1 206 667 7983; mbleakle@fhcrc.org Transplantation as a curative strategy for high-risk leukemia Allogeneic hematopoietic stem cell transplantation (HCT) is curative for many children with life-threatening, chemotherapy-resistant leukemia. HCT works by two major mechanisms: high-intensity chemotherapy, or chemoradiotherapy pretransplant conditioning; and an immunologic antileukemia effect mediated by donor lymphocytes in the graft, the ‘graftversus-leukemia effect’ (GVL). Survival rates for pediatric leukemia HCT recipients have steadily increased over time with current overall survival rates for pediatric acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) of >50%. The improvements in survival principally reflect major reductions in early postHCT treatment-related mortality (TRM) that have occurred as a result of better supportive care. The decrease in TRM in unrelated donor, cord blood (CBT) and mismatched family donor HCT has been particularly notable, and survival rates after ‘alternative donor HCT’ are now broadly comparable to HLA-matched sibling donor HCT. Unfortunately, relatively little reduction has been achieved in relapse rates, making relapse now the most frequent cause of failure of HCT for leukemia [1]. Relapse occurs in 10–30% of HCTs performed for pediatric leukemia in remission and has a dismal prognosis: the median survival of children with postHCT relapse is 4 months [2]. In order to further improve overall survival after allogeneic HCT for pediatric leukemia, novel strategies to address post-HCT leukemia relapse are crucial.