Haploidentical versus Matched Unrelated versus Matched Sibling Donor Hematopoietic Cell Transplantation with Post-Transplantation Cyclophosphamide

Authors

Rohtesh S Mehta
Rima M Saliba
Sassine Ghanem
Amin M Alousi
Gabriela Rondon
Paolo Anderlini
Gheath Al-Atrash
Qaiser Bashir
Chitra M Hosing
Jin S Im
Partow Kebriaei
Issa Khouri
David Marin
Yago Nieto
Amanda Olson
Betul Oran
Uday R Popat
Muzaffar H Qazilbash
Jeremy Ramdial
Neeraj Saini
Samer A Srour
Richard E Champlin
Katayoun Rezvani
Elizabeth J Shpall

Publication Date

7-1-2022

Journal

TransTransplantation and Cellular Therapy

Abstract

With the use of post-transplantation cyclophosphamide (PTCy), the outcomes of mismatched related donor hematopoietic cell transplantation (HCT) are now approaching those of matched donor HCT. Here we compared haploidentical donor HCT versus HLA-matched unrelated donor (MUD) HCT and HLA-identical sibling donor (MSD) HCT in a cohort in which all patients received PTCy for graft-versus-host disease (GVHD) prophylaxis. We included 661 patients (275 haploidentical, 246 MUD, and 140 MSD HCT). The most common diagnoses were acute myelogenous leukemia and myelodysplastic syndrome. In multivariate analysis, the haploidentical group was found to have significantly higher nonrelapse mortality (NRM) (hazard ratio [HR], 3.2; 95% confidence interval [CI], 2 to 4.9; P < .001) and inferior progression-free survival (HR, 1.8; 95% CI, 1.4 to 2.4; P < .001) and overall survival (OS; HR, 2.2; 95% CI, 1.6 to 3; P < .001) compared with the MUD group. Relapse was the most common cause of death in all groups. Among causes of NRM, the haploidentical group had more infection-related deaths and fewer GVHD-related deaths than the other groups. The haploidentical group also had a higher risk of viral and fungal infections, grade ≥3 hemorrhagic cystitis, and cardiovascular toxicities and slower reconstitution of CD4, CD8, and regulatory T cells but faster reconstitution of natural killer cells. In an exploratory analysis, older patients with older donors (>50 years for both) appeared to have particularly high NRM and lower OS in the haploidentical group compared with the other groups. Our data suggest that even with the use of PTCy, the outcomes of haploidentical HCT are inferior to those of HLA-matched donor HCT.

Keywords

Cyclophosphamide, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Humans, Leukemia, Myeloid, Acute, Siblings, Transplantation Conditioning, Transplantation, Haploidentical

DOI

10.1016/j.jtct.2022.04.020

PMID

35513252

PMCID

PMC10152475

PubMedCentral® Posted Date

7-1-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes