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 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 and severe cytokine release syndrome. 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.

Keywords:

• Haploidentical
• hematopoietic cell transplantation
• post-transplant cyclophosphamide
• cytokine release syndrome
• fludarabine
• melphalan

Disclosure statement

L.E., D.A.R.-G., J.F.D., J.R.A., T.F., R.A., and E.H. have no relevant conflicts to disclose.

Additional information

Funding

R.A. is supported by the American Society of Hematology Clinical Research Training Institute, the American Society of Hematology Research Training Award for Fellows, and the National Cancer Institute of the National Institutes of Health under Award Number R25 CA190190.