Donor telomeres and their magnitude of shortening post-allogeneic haematopoietic cell transplant impact survival for patients with early-stage leukaemia or myelodysplastic syndromeResearch in context
Summary: Background: Donor selection is a key success factor in allogeneic haematopoietic cell transplant (HCT). We evaluated the potential impact of donor leucocyte telomere length (LTL) and LTL shortening in recipients at three-month post-HCT (LTL-3MS) on the two-year HCT outcomes. Methods: We id...
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| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-04-01
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| Series: | EBioMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396425000854 |
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| Summary: | Summary: Background: Donor selection is a key success factor in allogeneic haematopoietic cell transplant (HCT). We evaluated the potential impact of donor leucocyte telomere length (LTL) and LTL shortening in recipients at three-month post-HCT (LTL-3MS) on the two-year HCT outcomes. Methods: We identified a cohort of 384 HCT recipients for early-stage leukaemia or myelodysplastic syndrome in the Blood and Marrow Transplant Clinical Trial Network protocol#1202 with blood samples collected three-month post-HCT. Blood samples from respective donors were available at the Centre for International Blood and Marrow Transplant Research biorepository. We used Cox proportional hazards models for statistical analyses. Findings: A better two-year overall survival (OS) was associated with longer donor LTL (adjusted-hazard ratio [HR] = 0.60, 95% confidence interval [CI] = 0.37–0.96, for LTL ≥6.7 kb vs LTL< 6.7 kb, p = 0.03), and higher LTL-3MS (HR = 0.52, 95% CI = 0.34–0.80, for LTL-3MS ≥ 230 vs < 230 bp, p = 0.003). Longer donor LTL was associated with a lower risk of non-relapse mortality (NRM; HR = 0.48, p = 0.05), while higher LTL-3MS was associated with lower relapse risk (HR for relapse risk = 0.53, p = 0.008). The adjusted 2-year cumulative risk of all-cause mortality was reduced by about half for patients with both donor LTL ≥6.7 kb and LTL-3MS ≥ 230 bp vs patients with neither characteristic (21% vs 41%, respectively; p < 0.0001). Interpretation: Selection of donors with longer LTL may improve HCT outcomes. Limited LTL shortening in recipients post-HCT may guide relapse prediction. Funding: The NCI intramural research program and NIH grant U01AG066529. |
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| ISSN: | 2352-3964 |