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 nonmalignant disorders. A dreaded complication is graft failure (GF), as it puts patients at high risk of infection and disease relapse. There are few contemporary data on the risks, outcomes, and economic burden of GF in pediatric patients. In this study, we address this gap by focusing on 14 years of transplant at our single center, for which data are compared in 2 time periods 2005 to 2010 (n = 146) and 2011 to 2018 (n = 144). In the 290 patients studied, the median age was 9.33 years, and 50.3% had malignant versus nonmalignant disease. Cell source included bone marrow (51%), cord blood (19.7%), unmanipulated peripheral blood stem cells (PBSCs; 12.1%), and CD34-selected PBSCs (17.2%). Twenty-one percent of patients had reduced-intensity conditioning (RIC), 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 and NNGF) was 6.6% and 3.8%, respectively. Multivariate analysis demonstrated alemtuzumab (odds ratio [OR], 6.256, P < .001) was the main variable associated with a higher rate of GF in both time periods, whereas RIC (OR, 11.8, P < .001) and cell source (CD34-selected PBSCs; OR, 4.22, P = .04) showed period-specific effects. Specifically, from time periods 1 to 2, cord blood transplants were discontinued at our center, with a concomitant increase in CD34-selected grafts and a shift from more episodes of NGF to NNGF. Overall survival was 69% in the entire HCT cohort and 50% among patients with GF. Survival among GF patients improved from time periods 1 to 2 (20% versus 80%, P = .001), potentially due to a 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 summary, GF remains a significant challenge in pediatric HCT and poses an economic burden on the health care system.