Risk Factors, Clinical Outcomes, and Cost-of-Care Related to Graft Failure in Pediatric Allogeneic Hematopoietic Cell Transplant Recipients

Abstract Allogeneic hematopoietic cell transplantation (HCT) has the capacity to cure numerous malignant and non-malignant disorders. A dreaded complication is graft failure (GF), as it puts patients at high risk of infection and disease relapse. There is little contemporary data on the risks, outcomes, and economic burden of graft failure in pediatric patients. In this study, we address this gap by focusing on fourteen years of transplant at our single-center, for which data are compared in two time periods: 2005-2010 (n= 146) and 2011-2018 (n = 144). In the 290 patients studied, the median age was 9.3 years. 50.3% had malignant vs. non-malignant disease. Cell source included: bone marrow (51%), cord blood (19.7%), unmanipulated peripheral blood cells (PBSC; 12.1%) and CD34-selected PBSCs (17.2%). 21% patients had reduced-intensity (RIC) conditioning, and 54.8% of transplants were fully HLA matched. Most patients received serotherapy with rabbit anti-thymocyte globulin (39.3%) or alemtuzumab (42.8%). The incidence of neutropenic and non-neutropenic GF (NGF & NNGF) was 6.6% and 3.8%, respectively. Multivariate analysis demonstrated alemtuzumab (OR = 6.256, p Overall survival was 69% in the entire HCT cohort and 50% among patients with GF. Survival among GF patients improved from time period 1 to 2 (20% vs. 80%, p = 0.001), potentially due to higher incidence of NNGF and increased ability to perform stem cell boosts from the same donor once cord blood transplants were phased out. Inpatient length of stay was consistently higher for patients with GF. Similar trends were seen for inpatient costs, although improvements were seen in our entire HCT population over time. In sum, GF remains a significant challenge in pediatric HCT and poses an economic burden on the health care system.