Faculty Collaboration Database

Related donor transplants: has posttransplantation cyclophosphamide nullified the detrimental effect of HLA mismatch? Blood Adv 2018 Jun 12;2(11):1180-1186

Date

05/26/2018

Pubmed ID

29794073

Pubmed Central ID

PMC5998932

DOI

10.1182/bloodadvances.2018018291

Scopus ID

2-s2.0-85051130706 (requires institutional sign-in at Scopus site)   33 Citations

Abstract

We sought to identify whether posttransplantation cyclophosphamide (PT-Cy) reduces or eliminates the detrimental impact of HLA mismatching on outcomes of HLA-haploidentical related donor transplantation for acute leukemia. Data from 2143 donor-recipient pairs (n = 218 haploidentical sibling; n = 218 offspring; n = 1707 HLA-matched sibling) with acute myeloid or lymphoblastic leukemia were studied. All received a calcineurin inhibitor for graft-versus-host disease (GVHD) prophylaxis while high-dose PT-Cy was also given to recipients of haploidentical transplant. Patient age correlated with donor-recipient relationship: haploidentical siblings donated to patients aged 18 to 54 years whereas offspring donated to patients aged 55 to 76 years. Therefore, transplant outcomes were examined separately in the 2 patient age groups. In patients aged 18 to 54 years, there were no significant differences in outcomes except chronic GVHD, which was lower after haploidentical sibling compared to HLA-matched sibling transplant (hazard ratio [HR], 0.63; P < .001). In patients aged 55 to 76 years, despite lower chronic GVHD (HR, 0.42; P < .001), graft failure (14% vs 6%; P = .003), nonrelapse mortality (HR, 1.48; P = .02), and overall mortality (HR, 1.32; P = .003) were higher after transplant from offspring compared with an HLA-matched sibling. These data demonstrate a superior outcome in older recipients when using an HLA-matched sibling instead of offspring, although there were differences in transplant platforms (GVHD prophylaxis and graft type) between the 2 groups. Validation of these findings requires a prospective randomized trial wherein the transplant platforms can be closely matched.

Author List

Robinson TM, Fuchs EJ, Zhang MJ, St Martin A, Labopin M, Keesler DA, Blaise D, Bashey A, Bourhis JH, Ciceri F, Ciurea SO, Devine SM, Mohty M, McCurdy SR, Milpied N, McNiece IK, Rocha V, Romee R, Socie G, Yakoub-Agha I, Soiffer RJ, Eapen M, Nagler A, Acute Leukemia Working Party of the European Society for Blood and Marrow Transplant and the Center for International Blood and Marrow Transplant Research

Authors

Mary Eapen MBBS, DCh, MRCPI, MS Professor in the Medicine department at Medical College of Wisconsin
Mei-Jie Zhang PhD Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acute Disease
Adolescent
Adult
Aged
Chronic Disease
Cyclophosphamide
Disease-Free Survival
Female
Graft vs Host Disease
HLA Antigens
Hematopoietic Stem Cell Transplantation
Humans
Leukemia
Male
Middle Aged
Survival Rate
Tissue Donors