Related donor transplants: has posttransplantation cyclophosphamide nullified the detrimental effect of HLA mismatch?

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.

• Authors: Tara M Robinson, Ephraim J Fuchs, Mei-Jie Zhang, Andrew St Martin, Myriam Labopin, Daniel A Keesler, Didier Blaise, Asad Bashey, Jean-Henri Bourhis, Fabio Ciceri, Stefan O Ciurea, Steven M Devine, Mohamad Mohty, Shannon R McCurdy, Noel Milpied, Ian K McNiece, Vanderson Rocha, Rizwan Romee, Gerard Socie, Ibrahim Yakoub-Agha, Robert J Soiffer, Mary Eapen, Arnon Nagler, Acute Leukemia Working Party of the European Society for Blood and Marrow Transplant and the Center for International Blood and Marrow Transplant Research
• Journal: Blood advances (Blood Adv) Vol. 2 Issue 11 Pg. 1180-1186 (06 12 2018) ISSN: 2473-9537 [Electronic] United States
• PMID: 29794073 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
• Copyright: © 2018 by The American Society of Hematology.

Chemical References

• HLA Antigens
• Cyclophosphamide

Topics

• Acute Disease
• Adolescent
• Adult
• Aged
• Chronic Disease
• Cyclophosphamide (administration & dosage)
• Disease-Free Survival
• Female
• Graft vs Host Disease (mortality, prevention & control)
• HLA Antigens
• Hematopoietic Stem Cell Transplantation
• Humans
• Leukemia (mortality, therapy)
• Male
• Middle Aged
• Survival Rate
• Tissue Donors