Abstract
Donor stem cell health may be critically important to the success of hematopoietic stem cell transplantation (HSCT). Herein, we performed this systematic review and meta-analysis including meta-regression to assess the impact of donor-engrafted clonal hematopoiesis (CH) in allogeneic HSCT (allo-HSCT) and impact of pre-transplant CH in autologous HSCT (auto-HSCT). We applied random-effects models to analyze 5 allo-HSCT studies with 3192 donor-recipient pairs and 9 auto-HSCT studies with 2854 patients. We found that donor-engrafted CH after allo-HSCT decreased the risk of disease relapse [Hazard Ratio (HR) = 0.79, 95% Confidence Interval (CI): (0.67, 0.93)], but did not affect overall survival (OS) [HR = 0.91, 95% CI: (0.75, 1.11)], progression-free survival (PFS) [HR = 0.94, 95% CI: (0.63, 1.41)], or non-relapse mortality [HR = 1.06, 95% CI: (0.81, 1.39)]. In contrast, pre-transplant CH in auto-HSCT recipients resulted in inferior OS [HR = 1.30, 95% CI: (1.16, 1.46)], inferior PFS [HR = 1.35, 95% CI: (1.18, 1.54)], and higher risk for therapy-related myeloid neoplasm [HR = 4.85, 95% CI: (2.39, 9.82)] when compared to auto-HSCT recipients without CH. This study sheds light onto the debate about prospective “CHIP screening” for stem cell donors and addresses the impact of CH as a transmissible phenomenon.
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All data generated or analyzed during this study are included in this published article and its supplementary information files.
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Funding
SAP received research funding in 2022-23 from the UMass Center for Clinical and Translational Science (CCTS) Pilot Project Program grant (NIH / NCATS Grant UL1TR001453). SAP received travel support in 2024 from AAMDSIF. LDW is supported by the Edward P Evans Foundation for MDS, American Society of Hematology/Robert Wood Johnson Foundation AMFDP and Breakthrough Cancer Foundation. JT received the 2022 ASH Physician-Scientist Career Development Award. TYZ receives research funding from NIH/NCI grant 5K08CA248940-04. CY received research funding in 2022-23 from the NIH/NIDCR Grant R01DE029963 and the NIH/NIMH Grant P50MH129701. These are unrelated to the present work, and the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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YX and SAP conceived the manuscript. YX, VK, and SAP wrote the manuscript. YX and XW developed the search criteria. XW, LDW, JMG, JT, TYZ, CY, and RL gave critical insight into analysis and critically revised the manuscript. Under CY’s supervision, YX performed and analyzed meta-analyses and meta-regression. YX, CY, and SAP gave final approval.
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SAP served on the Myelodysplastic Syndrome advisory board and the Acute Myeloid Leukemia advisory board for Bristol Myers Squibb and served on the Multiple Myeloma advisory board for Pfizer. LDW reports consulting fees from AbbVie, Vertex and Sobi all unrelated to the present work. JMG served on an MDS Advisory Board for Novartis and holds US Patent No. 9012215, US Patent No. 10222376, and US Patent No. 11209435. Other authors have no conflicts of interest.
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All methods were performed in accordance with the relevant guidelines and regulations. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were strictly followed. Informed consent is not applicable as this was a meta-analysis. There are no patient identifiable images in this manuscript.
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Xie, Y., Kazakova, V., Weeks, L.D. et al. Effects of donor-engrafted clonal hematopoiesis in allogeneic and autologous stem cell transplantation: a systematic review and meta-analysis. Bone Marrow Transplant (2024). https://doi.org/10.1038/s41409-024-02403-2
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DOI: https://doi.org/10.1038/s41409-024-02403-2