Associations of minor histocompatibility antigens with outcomes following allogeneic hematopoietic cell transplantation
Abstract
The role of minor histocompatibility antigens (mHAs) in mediating graft versus leukemia and graft versus host disease (GvHD) following allogeneic hematopoietic cell transplantation (alloHCT) is recognized but not well‐characterized. By implementing improved methods for mHA prediction in two large patient cohorts, this study aimed to comprehensively explore the role of mHAs in alloHCT by analyzing whether (1) the number of predicted mHAs, or (2) individual mHAs are associated with clinical outcomes. The study population consisted of 2249 donor–recipient pairs treated for acute myeloid leukemia and myelodysplastic syndrome with alloHCT. A Cox proportional hazard model showed that patients with a class I mHA count greater than the population median had an increased hazard of GvHD mortality (hazard ratio [HR] = 1.39, 95% confidence interval [CI] = 1.01, 1.77, p = .046). Competing risk analyses identified the class I mHAs DLRCKYISL (GSTP), WEHGPTSLL (CRISPLD2), and STSPTTNVL (SERPINF2) were associated with increased GVHD mortality (HR = 2.84, 95% CI = 1.52, 5.31, p = .01), decreased leukemia‐free survival (LFS) (HR = 1.94, 95% CI = 1.27, 2.95, p = .044), and increased disease‐related mortality (DRM) (HR = 2.32, 95% CI = 1.5, 3.6, p = .008), respectively. One class II mHA YQEIAAIPSAGRERQ (TACC2) was associated with increased risk of treatment‐related mortality (TRM) (HR = 3.05, 95% CI = 1.75, 5.31, p = .02). WEHGPTSLL and STSPTTNVL were both present within HLA haplotype B*40:01‐C*03:04 and showed a positive dose–response relationship with increased all‐cause mortality and DRM and decreased LFS, indicating these two mHAs contribute to the risk of mortality in an additive manner. Our study reports the first large‐scale investigation of the associations of predicted mHA peptides with clinical outcomes following alloHCT.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 13, 2023
- Source ID
- 10.1002/ajh.26925
Entities
People
- Amy Webb
- Benjamin G Vincent
- Christopher A. Haiman
- Guy Brock
- Hancong Tang
- Kelly Olsen
- Lara E. Sucheston‐campbell
- Loreall Pooler
- Marcelo C Pasquini
- Othmane Jadi
- Paul Armistead
- Philip L. Mccarthy
- Qianqian Zhu
- Stephen R. Spellman
- Steven Vensko
- Theresa Hahn
- Xin Sheng
- Yiwen Wang
Organizations
- Health Resources and Services Administration
- Medical College of Wisconsin
- National Cancer Institute
- National Heart, Lung, and Blood Institute
- National Institute of Allergy and Infectious Diseases
- National Marrow Donor Program
- Office of Naval Research
- Ohio State University
- Roswell Park Comprehensive Cancer Center
- Stanford University
- University of North Carolina School of Medicine
- University of North Carolina at Chapel Hill
- University of Southern California