Outcomes after Allogeneic Hematopoietic Stem Cell Transplantation for Pediatric Acute Myeloid Leukemia in the Contemporary Era

Abstract

High risk or relapsed pediatric acute myeloid leukemia (AML) is potentially curable with allogeneic hematopoietic stem cell transplantation (HSCT). Significant improvements have been made with supportive care practices, but there are limited HSCT outcome data for pediatric AML patients in the contemporary era. We report retrospective data in 87 pediatric patients with high risk or relapsed AML, who underwent HSCT at a single institution between 2008 and 2018. The median age at time of HSCT was 8 years (range: 0.6-20 years). Forty three patients (49%) were transplanted in CR1, 18 (21%) in CR2, and 26 (30%) with active disease (defined as any evidence of disease at the time of HSCT). Patients were transplanted using matched related (MRD, n=21), matched unrelated (MUD, n=25), mismatched unrelated (MMUD, n=15), haplo-identical (haplo, n=12) or umbilical cord blood (UCB, n=14) grafts. The majority of patients (78/87, 90%) received myeloablative conditioning. MRD and UCB graft recipients did not receive serotherapy. All other graft recipients (n=52) received serotherapy, the majority using an alemtuzumab-based conditioning regimen, 42/52 (81%). Haplo-identical transplants were performed using CD34+ selected grafts. Three-year overall survival (OS) and disease free survival (DFS) for the entire cohort were 52% (95% CI: 41-62%) and 49% (95% CI: 38-59%) respectively. OS differed significantly according to disease status at time of transplant (p=0.018), with 3 year OS: 60%, (95% CI: 43-74%) for those in CR1, 56%, (95% CI: 31-75%) for those in CR2 and 34% (95% CI: 17-52%) for those with active disease. OS differed by donor type (p=0.058). OS was comparable for patients with MRD (71%, 95% CI: 46-86%) and 10/10 MUD (59%, 95% CI: 37-75%) (p=0.67). Patients with alternate donor sources had worse outcomes (MMUD 33%, 95% CI: 10-59%; UCB 43%, 95% CI: 18-66%; Haplo 33%, 95% CI: 10-59%) as compared to MRD (MMUD vs MRD, p=0.042, UCB vs MRD, p=0.046, haplo vs MRD p=0.017). There was a low incidence of Grade III-IV acute GVHD (8%, n=7) and extensive chronic GVHD (9%, n=7) likely secondary to the use of alemtuzumab-based conditioning regimens. The 3-year non-relapse mortality was low at 11% (95% CI: 5-19%). The primary cause of death was relapse, with a 3-year cumulative incidence of relapse of 40%, (95% CI: 30-50%). Patients with active disease at HSCT had significantly higher cumulative incidence of relapse (sHR: 2.42, 95% CI: 1.18-4.95, p=0.016) compared to patients in remission. In the contemporary era, outcomes after allogeneic HSCT are comparable for MRD and 10/10 MUD for pediatric AML. Myeloablative and alemtuzumab based conditioning regimens were well tolerated with low rates of NRM and GVHD. Relapse remains the major cause of treatment failure. Future trials evaluating use of cellular therapies and targeted agents post-HSCT will be needed.