次要组织相容性抗原与同种异体造血细胞移植后结果的关联,American Journal of Hematology

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次要组织相容性抗原与同种异体造血细胞移植后结果的关联
American Journal of Hematology ( IF 10.1 ) Pub Date : 2023-04-13 , DOI: 10.1002/ajh.26925
Othmane Jadi ₁ , Hancong Tang ₂ , Kelly Olsen ₁ , Steven Vensko ₁ , Qianqian Zhu ₃ , Yiwen Wang ₄ , Christopher A Haiman ₅ , Loreall Pooler ₆ , Xin Sheng ₅ , Guy Brock ₇ , Amy Webb ₇ , Marcelo C Pasquini ₈ , Philip L McCarthy ₃ , Stephen R Spellman ₉ , Theresa Hahn ₁₀ , Benjamin Vincent _{1,

11} , Paul Armistead _{1,

11} , Lara E Sucheston-Campbell _{2,

12}

Affiliation

Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, CB# 7295, Chapel Hill, North Carolina, USA.
College of Pharmacy, The Ohio State University, Columbus, Ohio, USA.
Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA.
Quantitative Sciences Unit, Department of Medicine, Stanford University, Palo Alto, California, USA.
Department of Preventive Medicine, University of Southern California, Los Angeles, California, USA.
The Center for Genetic Epidemiology, University of Southern California, Los Angeles, California, USA.
Department of Biomedical Informatics, The Ohio State University, Columbus, Ohio, USA.
Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Center for International Blood and Marrow Transplant Research, National Marrow Donor Program, Minneapolis, Minnesota, USA.
Department of Cancer Prevention & Control, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA.
Division of Hematology, Department of Medicine, UNC School of Medicine, Chapel Hill, North Carolina, USA.
College of Veterinary Medicine, The Ohio State University, Columbus, Ohio, USA.

次要组织相容性抗原 (mHA) 在介导同种异体造血细胞移植 (alloHCT) 后移植物抗白血病和移植物抗宿主病 (GvHD) 中的作用已得到认可，但尚未得到充分表征。通过在两个大型患者队列中实施改进的 mHA 预测方法，本研究旨在通过分析 (1) 预测的 mHA 数量或 (2) 个体 mHA 是否与临床结果相关，全面探讨 mHA 在 alloHCT 中的作用。研究人群由 2249 对接受异基因 HCT 治疗的急性髓系白血病和骨髓增生异常综合征的供体-受体对组成。Cox 比例风险模型显示，I 类 mHA 计数大于人群中位数的患者 GvHD 死亡率风险增加（风险比 [HR] = 1.39，95% 置信区间 [CI] = 1.01, 1.77，p = . 046）。竞争性风险分析确定 I 类 mHA DLRCKYISL ( GSTP )、WEHGPTSLL ( CRISPLD2 ) 和 STSPTTNVL ( SERPINF2 ) 与 GVHD 死亡率增加（HR = 2.84，95% CI = 1.52, 5.31， p = .01）、白血病减少相关无生存期 (LFS)（HR = 1.94，95% CI = 1.27, 2.95，p = .044），以及疾病相关死亡率 (DRM) 增加（HR = 2.32，95% CI = 1.5, 3.6，p = . 008），分别。一种 II 类 mHA YQEIAAIPSAGRERQ ( TACC2 ) 与治疗相关死亡率 (TRM) 风险增加相关 (HR = 3.05, 95% CI = 1.75, 5.31, p = .02)。WEHGPTSLL 和 STSPTTNVL 均存在于 HLA 单倍型 B*40:01-C*03:04 中，并与全因死亡率和 DRM 增加以及 LFS 降低呈正剂量反应关系，表明这两种 mHA 会增加死亡风险以累加的方式。我们的研究报告了对预测的 mHA 肽与 alloHCT 后临床结果之间关系的首次大规模调查。

"点击查看英文标题和摘要"

Associations of minor histocompatibility antigens with outcomes following allogeneic hematopoietic cell transplantation

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.

更新日期：2023-04-13

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