Donor leukocyte telomere length emerges as a prognostic factor for transplantation outcomes

Hengwei Wu; Jing Yu; Yang Cao; Ruowen Wei; Wei Shi; Yunxian Yu; Zhuoyue Shi; Jimin Shi; Yi Luo; Jian Yu; Xiaoyu Lai; Lizhen Liu; Yamin Tan; Huarui Fu; Pengxu Qian; Wenming Shi; Zhongzheng Zheng; Xiaoxia Hu; He Huang; Yanmin Zhao

doi:10.1016/j.xinn.2025.101147

Donor leukocyte telomere length emerges as a prognostic factor for transplantation outcomes

Innovation (Camb). 2025 Oct 24;7(3):101147. doi: 10.1016/j.xinn.2025.101147. eCollection 2026 Mar 2.

Authors

Hengwei Wu^{1

2

3}, Jing Yu^{1

2

3}, Yang Cao⁴, Ruowen Wei⁵, Wei Shi⁵, Yunxian Yu⁶, Zhuoyue Shi^{1

2

3}, Jimin Shi^{1

2

3}, Yi Luo^{1

2

3}, Jian Yu^{1

2

3}, Xiaoyu Lai^{1

2

3}, Lizhen Liu^{1

2

3}, Yamin Tan⁷, Huarui Fu^{1

2

3}, Pengxu Qian^{1

2

3}, Wenming Shi⁸, Zhongzheng Zheng⁹, Xiaoxia Hu¹⁰, He Huang^{1

2

3}, Yanmin Zhao^{1

2

3}

Affiliations

¹ Bone Marrow Transplantation Center of the First Affiliated Hospital & Liangzhu Laboratory, Zhejiang University School of Medicine, Hangzhou 310006, China.
² Institute of Hematology, Zhejiang University, Hangzhou 310058, China.
³ Zhejiang Province Engineering Research Center for Stem Cell and Immunity Therapy, Hangzhou 311121, China.
⁴ Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
⁵ Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
⁶ Department of Epidemiology and Statistics, School of Public Health, Zhejiang University, Hangzhou 310058, China.
⁷ Department of Hematology, Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou 310022, China.
⁸ School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 9990077, China.
⁹ Shanghai Tissuebank Precision Medicine Co., Ltd, Shanghai 201110, China.
¹⁰ Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

Abstract

Younger donors are preferred in allogeneic hematopoietic stem cell transplantation (allo-HSCT), but this preference may limit access for patients whose only available donors are older. This study evaluated whether donor leukocyte telomere length (LTL), in conjunction with donor age, refines donor selection strategies to improve outcomes in recipients with acute leukemia. The discovery analysis included 1,049 acute leukemia patients who underwent allo-HSCT at the First Affiliated Hospital of Zhejiang University School of Medicine, while the replication cohort included 153 recipients from three additional centers. Donor LTL was measured using real-time quantitative PCR and categorized into quartiles: short (Q1) and long (Q2-Q4). Donor age was prespecified as <40 (younger) vs. ≥40 (older) years based on clinical practice. Long donor LTL was associated with a lower cumulative incidence of relapse (CIR), improved overall survival (OS), and better relapse-free survival (RFS) in allo-HSCT recipients. Recipients of grafts from donors aged ≥40 years with short LTL had higher CIR (adjusted hazard ratio [aHR] = 1.51; 95% confidence interval [CI], 1.04-2.19), worse OS (aHR = 1.76; 95% CI, 1.20-2.58), and worse RFS (aHR = 1.53; 95% CI, 1.06-2.20) compared with recipients of grafts from donors <40 years. Immune cell profiling showed that older donors with short LTL had more CD8⁺CD57⁺HLA-DR^- cells. In the replication cohort, recipients of grafts from older donors with long LTL had outcomes comparable with those of recipients with younger donors, while those with older donors and short LTL had inferior outcomes. These findings support considering donor LTL as a supplemental factor during donor evaluation, especially when younger donors are not available.

Keywords: acute leukemia; allogeneic hematopoietic stem cell transplantation; donor selection; leukocyte telomere length.