Post-Transplant Cyclophosphamide Improves Survival in HLA-DPB1 Mismatched Unrelated Donor Allogeneic Transplantation

Authors

• S.R. McCurdy, University of Pennsylvania, Philadelphia, PA
• S.R. Solomon, Northside Hospital Cancer Institute, Atlanta, GA
• B.C. Shaffer, Memorial Sloan Kettering Cancer Center, New York, NY
• M. He, Center for International Blood and Marrow Transplant Research, Minneapolis, MN
• Y-T. Bolon, Center for International Blood and Marrow Transplant Research, Minneapolis, MN
• A.G. Blouin, Memorial Sloan Kettering Cancer Center, New York, NY
• A. Keyzner, Icahn School of Medicine at Mount Sinai, New York, NY
• F.A. Socola, Tulane University School of Medicine, New Orleans, LA
• U. Ibrahim, Icahn School of Medicine at Mount Sinai, New York, NY
• J. Zou, MD Anderson Cancer Center, Houston, TX
• Hana Safah, LSU Health Sciences Center - New Orleans
• N. Saba, Tulane University School of Medicine, New Orleans, LA
• S. Gadalla, National Cancer Institute, Rockville, IL
• M.-A. Perales, Memorial Sloan Kettering Cancer Center, New York, NY
• S. Paczesny, Medical University of South Carolina, Charleston, SC
• S.G.E. Marsh, University College London Cancer Institute, London, United Kingdom
• E.W. Petersdorf, University of Washington, Seattle, WA
• T. Wang, Medical College of Wisconsin, Milwaukee, WI
• S.J. Lee, Medical College of Wisconsin, Milwaukee, WI
• E.J. Fuchs, Johns Hopkins University, Baltimore, MD

Document Type

Article

Publication Date

10-1-2025

Publication Title

Transplantation and Cellular Therapy

Abstract

HLA-DPB1 mismatching is common in unrelated donor (URD) hematopoietic cell transplantation (HCT) and increases graft-versus-host disease (GVHD) when using methotrexate and tacrolimus (MTX/Tac)-based GVHD prophylaxis. Historically, national and international guidelines recommended prioritizing HLA-DPB1 matching in URD selection. The impact of HLA-DPB1 matching in URD HCT when using post-transplantation cyclophosphamide (PTCy) has been understudied. Our primary endpoint was the association of GVHD-prophylaxis strategy with overall survival (OS) after T cell-replete 12/12 HLA-matched or HLA-DPB1 permissive or non-permissive (NP) mismatch (MM) (defined by the T-cell-epitope groups model) URD HCT. GVHD-free, relapse-free survival (GRFS) was our key secondary endpoint. This was a retrospective cohort study using the Center for International Blood and Marrow Transplant Research (CIBMTR) database. Recipients underwent a first HCT from 2015-2020 for acute leukemia or myelodysplastic syndrome using either HLA-DPB1 NP MM (n = 329), permissive MM (n = 992), or 12/12 HLA-matched (n = 300) URD with PTCy ± mycophenolate mofetil and/or a calcineurin inhibitor, or HLA-DPB1 NP MM (n = 709), permissive MM (n = 2,395), or 12/12 HLA-matched (n = 911) URD with MTX/Tac. HLA-DPB1 NP MM HCT with MTX/Tac was associated with higher treatment-related mortality (TRM) (hazard ratio [HR]: 1.64, 1.08-2.49, P = .019), lower relapse (HR: 0.73, 0.59-0.92, P = .0073), inferior OS (HR: 1.27, 1.03 -1.57, P = .023), and worse GRFS (HR: 1.61, 1.34-1.94, P < .0001) when compared with HLA-DPB1 NP MM HCT with PTCy. Adjusted 1-yr estimates for GRFS were 54% (95% confidence interval [CI]: 49-60%) for PTCy and 40% (CI: 37-44%) for MTX/Tac. For permissive MM URD HCT, MTX/Tac was associated with inferior GRFS (HR 1.54, CI: 1.36-1.76, P < .0001) when compared with PTCy. When using PTCy, there were no significant differences in the above outcomes for HLA–DPB1 NP MM, HLA-DPB1 permissive MM, or 12/12 HLA-matched URD HCT. PTCy should be the preferred GVHD prophylaxis strategy for HLA-DPB1 MM URD HCT. Furthermore, within PTCy platforms, survival is comparable across HLA-DPB1 match and thus NP mismatching at HLA-DPB1 should not be avoided in URD selection when using PTCy.

First Page

74.e1

Last Page

74.e14

PubMed ID

41043776

Volume

32

Issue

1

Rights

© 2025 The American Society for Transplantation and Cellular Therapy

Recommended Citation

McCurdy, S.R.; Solomon, S.R.; Shaffer, B.C.; He, M.; Bolon, Y-T.; Blouin, A.G.; Keyzner, A.; Socola, F.A.; Ibrahim, U.; Zou, J.; Safah, Hana; Saba, N.; Gadalla, S.; Perales, M.-A.; Paczesny, S.; Marsh, S.G.E.; Petersdorf, E.W.; Wang, T.; Lee, S.J.; and Fuchs, E.J., "Post-Transplant Cyclophosphamide Improves Survival in HLA-DPB1 Mismatched Unrelated Donor Allogeneic Transplantation" (2025). School of Medicine Faculty Publications. 5171.
https://digitalscholar.lsuhsc.edu/som_facpubs/5171
10.1016/j.jtct.2025.09.048