Donor telomeres and their magnitude of shortening post-allogeneic haematopoietic cell transplant impact survival for patients with early-stage leukaemia or myelodysplastic syndrome.

IF 9.7 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

EBioMedicine Pub Date : 2025-03-08 DOI:10.1016/j.ebiom.2025.105641

Shahinaz M Gadalla, Hormuzd A Katki, Tsung-Po Lai, Paul L Auer, Casey L Dagnall, Caitrin Bupp, Amy A Hutchinson, James J Anderson, Kyra J W Mendez, Stephen R Spellman, Valerie Stewart, Sharon A Savage, Stephanie J Lee, John E Levine, Wael Saber, Abraham Aviv

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引用次数: 0

Abstract

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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来源期刊

EBioMedicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology

CiteScore

17.70

自引率

0.90%

发文量

579

审稿时长

5 weeks

期刊介绍： eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.