Increased Early Mortality After Fludarabine and Melphalan Conditioning with Peripheral Blood Grafts in Haploidentical Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide

Abstract Due to the evolving use of haploidentical donor grafts in hematopoietic cell transplantation, there is increased need to better understand the risks and benefits of using bone marrow versus peripheral blood grafts, as well as how specific pre-transplantation conditioning regimens impact patient safety and treatment outcomes. We performed a retrospective analysis of 38 patients at two centers who specifically underwent haploidentical hematopoietic cell transplantation using fludarabine plus melphalan-based conditioning regimens with post-transplant cyclophosphamide and peripheral blood donor grafts. We observed an unexpectedly high rate of early non-relapse mortality of 21% at 100 days and 34% at 1-year. In addition, 40% of all patients suffered from severe cytokine release syndrome and 45% of all patients suffered from kidney injury, often necessitating renal replacement therapy. The poor outcomes with 1-year overall survival of 34%, disease-free survival of 29%, and non-relapse mortality of 34% motivate us to reconsider the appropriateness of the combination of fludarabine and melphalan conditioning with T-cell replete peripheral blood grafts in the setting of haploidentical hematopoietic cell transplant with post-transplant cyclophosphamide.