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Donor age ≥50 years combined with donor-CI ≥3 identifies a high-risk cohort for adverse outcomes after allogeneic hematopoietic stem cell transplantation in B-cell acute lymphoblastic leukemia

Bone Marrow Transplantation (2026)Cite this article

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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for B-cell acute lymphoblastic leukemia (B-ALL), but outcomes are limited by graft-versus-host disease (GVHD) and relapse. Donor age is a well-established prognostic factor, with advanced age linked to immunosenescence and inferior survival. However, the impact of donor comorbidities (Donor-CI) on outcomes remains unclear, as prior studies have not demonstrated standalone prognostic value [1]. We hypothesized that Donor-CI synergizes with advanced age to stratify risk—driven by the “double-hit” of immunosenescence (dysregulated immunity and pro-inflammatory state) and comorbidity-associated chronic inflammation—creating a scenario where neither factor alone is sufficient to worsen outcomes, but their combination impairs graft function. To test this synergistic effect, we evaluated a composite metric integrating both Donor-CI and donor age, with the primary objective of validating its ability to identify a high-risk donor cohort.

We conducted a single-center retrospective study of 458 consecutive B-ALL patients who underwent allo-HSCT with haploidentical or matched sibling donors between January 2019 and December 2021. The baseline characteristics, stratified by the composite Donor-CI/age groups, are detailed in Supplementary Table 1. Exclusion criteria were matched unrelated/cord blood donors or missing key data. The comorbidity for each donor was calculated based on a standardized HCT-CI scoring system (detailing the specific comorbidities and weights, e.g., as defined by Sorror et al. [2]). All HCT-CI components were systematically assessed via two primary data sources: (1) mandatory pre-donation health records (including detailed medical history, physical examination, and laboratory/imaging studies such as pulmonary function tests, electrocardiogram, and echocardiogram) and (2) a structured donor health questionnaire querying all HCT-CI-related conditions (e.g., cardiac, pulmonary, hepatic, renal disease, diabetes). Feasibility was high (96.7% capture of components), and missing/uncertain data (e.g., unreported rare conditions like prior solid tumor) were conservatively scored as 0 (absent) to avoid overestimating comorbidity burden. Donors were stratified by Donor-CI (0-2 vs. ≥3) and age (≥50 vs. <50 years, optimal cutoff via ROC analysis: AUC = 0.62, Youden index=0.29) into four groups: Group 1 (CI ≥ 3 + age≥50, n = 20), Group 2 (CI ≥ 3 + age<50, n = 56), Group 3 (CI0-2 + age≥50, n = 93), Group 4 (CI0-2 + age<50, n = 289). Primary endpoint was overall survival (OS); secondary endpoints included GVHD, relapse, and leukemia-free survival (LFS). Statistical analyses used Kaplan-Meier, Fine-Gray, and Cox regression models, with bootstrap resampling (1000 iterations) to assess stability of results for the small Group 1.

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Acknowledgements

The authors thank all the doctors at the institute who participated in this study for providing the follow-up samples and information.

Funding

This work was partly supported by the National Key Research and Development Program of China (No. 2023YFC2508905), the Noncommunicable Chronic Diseases-National Science and Technology Major Project (2026ZD0553900), the National Natural Science Foundation of China (82470214&82270227), Beijing Research Ward Excellence Program (BRWEP2024W134080102), Major Program of the National Natural Science Foundation of China (No.82293630&82530009), Beijing Municipal Science & Technology Commission (No. Z211100002921071), Beijing Municipal Science & Technology Commission, Administrative Commission of Zhongguancun Science Park (No. Z241100009024043).

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Authors and Affiliations

  1. Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing, China

    Ning Wu, Jun Kong, Meng Lv, Xiao-Dong Mo, Yu-Qian Sun, Yi-Fei Cheng, Lan-Ping Xu, Xiao-Hui Zhang, Xiao-Jun Huang & Yu Wang

  2. Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China

    Xiao-Jun Huang

  3. State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, China

    Xiao-Jun Huang

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  1. Ning Wu
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Contributions

YW and XH designed the research and revised the paper. NW analyzed the data and wrote the paper. JK, ML, XM, YS, YC, LX and XZ collected and analyzed data. All authors contributed to the article and approved the submitted version.

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Correspondence to Yu Wang.

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Supplementary information

Incidences of GVHD and probability of GRFS According to Composite Donor-CI/Age Groups. (download JPG )

Transplant Outcomes Stratified by Composite Donor-CI/Age Groups. (download JPG )

GVHD Outcomes Stratified by Donor-CI Alone. (download JPG )

Transplant Outcomes Stratified by Donor-CI Alone. (download JPG )

GVHD and GRFS Outcomes Stratified by Composite Donor-CI/Age Metrics. (download JPG )

Transplant Outcomes Stratified by Composite Donor-CI/Age Groups. (download JPG )

Patient characteristics (grouped by Donor-CI and donor age) (download XLSX )

Cause of death (grouped by Donor-CI and donor age) (download XLSX )

Patient characteristics (grouped by Donor-CI alone) (download XLSX )

Cause of death (grouped by Donor-CI alone) (download XLSX )

Complications and outcomes after allo-HSCT (grouped by Donor-CI alone) (download XLSX )

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Wu, N., Kong, J., Lv, M. et al. Donor age ≥50 years combined with donor-CI ≥3 identifies a high-risk cohort for adverse outcomes after allogeneic hematopoietic stem cell transplantation in B-cell acute lymphoblastic leukemia. Bone Marrow Transplant (2026). https://doi.org/10.1038/s41409-026-02844-x

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