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...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-04-01
|
| Series: | EBioMedicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396425000854 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850028257374633984 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Shahinaz M. Gadalla |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-8aa6a6a018574ccbbcbc4bd6e4881fcd |
| institution | DOAJ |
| issn | 2352-3964 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj-art-8aa6a6a018574ccbbcbc4bd6e4881fcd2025-08-20T02:59:52ZengElsevierEBioMedicine2352-39642025-04-0111410564110.1016/j.ebiom.2025.105641Donor telomeres and their magnitude of shortening post-allogeneic haematopoietic cell transplant impact survival for patients with early-stage leukaemia or myelodysplastic syndromeResearch in contextShahinaz M. Gadalla0Hormuzd A. Katki1Tsung-Po Lai2Paul L. Auer3Casey L. Dagnall4Caitrin Bupp5Amy A. Hutchinson6James J. Anderson7Kyra J.W. Mendez8Stephen R. Spellman9Valerie Stewart10Sharon A. Savage11Stephanie J. Lee12John E. Levine13Wael Saber14Abraham Aviv15Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA; Corresponding author. Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, 9609 Medical Center Drive, Room 6E-452, Rockville, MD, 20850, USA.Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USACenter of Human Development and Aging, New Jersey Medical School, Rutgers, NJ, USADivision of Biostatistics, Institute for Health and Equity, and Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USADivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA; Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research, Rockville, MD, USACenter for International Blood and Marrow Transplant Research, NMDP, Minneapolis, MN, USADivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA; Cancer Genomics Research Laboratory, Frederick National Laboratory for Cancer Research, Rockville, MD, USACollege of the Environment, University of Washington, Seattle, WA, USADivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USACenter for International Blood and Marrow Transplant Research, NMDP, Minneapolis, MN, USACenter for International Blood and Marrow Transplant Research, NMDP, Minneapolis, MN, USADivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USACenter for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI, USA; Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USATisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USACenter for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI, USA; Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, USACenter of Human Development and Aging, New Jersey Medical School, Rutgers, NJ, USASummary: 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.http://www.sciencedirect.com/science/article/pii/S2352396425000854TelomeresTelomere lengthHaematopoietic cell transplantDonor selectionRelapse |
| spellingShingle | 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 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 EBioMedicine Telomeres Telomere length Haematopoietic cell transplant Donor selection Relapse |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Telomeres Telomere length Haematopoietic cell transplant Donor selection Relapse |
| url | http://www.sciencedirect.com/science/article/pii/S2352396425000854 |
| work_keys_str_mv | AT shahinazmgadalla donortelomeresandtheirmagnitudeofshorteningpostallogeneichaematopoieticcelltransplantimpactsurvivalforpatientswithearlystageleukaemiaormyelodysplasticsyndromeresearchincontext AT hormuzdakatki donortelomeresandtheirmagnitudeofshorteningpostallogeneichaematopoieticcelltransplantimpactsurvivalforpatientswithearlystageleukaemiaormyelodysplasticsyndromeresearchincontext AT tsungpolai donortelomeresandtheirmagnitudeofshorteningpostallogeneichaematopoieticcelltransplantimpactsurvivalforpatientswithearlystageleukaemiaormyelodysplasticsyndromeresearchincontext AT paullauer donortelomeresandtheirmagnitudeofshorteningpostallogeneichaematopoieticcelltransplantimpactsurvivalforpatientswithearlystageleukaemiaormyelodysplasticsyndromeresearchincontext AT caseyldagnall donortelomeresandtheirmagnitudeofshorteningpostallogeneichaematopoieticcelltransplantimpactsurvivalforpatientswithearlystageleukaemiaormyelodysplasticsyndromeresearchincontext AT caitrinbupp donortelomeresandtheirmagnitudeofshorteningpostallogeneichaematopoieticcelltransplantimpactsurvivalforpatientswithearlystageleukaemiaormyelodysplasticsyndromeresearchincontext AT amyahutchinson donortelomeresandtheirmagnitudeofshorteningpostallogeneichaematopoieticcelltransplantimpactsurvivalforpatientswithearlystageleukaemiaormyelodysplasticsyndromeresearchincontext AT jamesjanderson donortelomeresandtheirmagnitudeofshorteningpostallogeneichaematopoieticcelltransplantimpactsurvivalforpatientswithearlystageleukaemiaormyelodysplasticsyndromeresearchincontext AT kyrajwmendez donortelomeresandtheirmagnitudeofshorteningpostallogeneichaematopoieticcelltransplantimpactsurvivalforpatientswithearlystageleukaemiaormyelodysplasticsyndromeresearchincontext AT stephenrspellman donortelomeresandtheirmagnitudeofshorteningpostallogeneichaematopoieticcelltransplantimpactsurvivalforpatientswithearlystageleukaemiaormyelodysplasticsyndromeresearchincontext AT valeriestewart donortelomeresandtheirmagnitudeofshorteningpostallogeneichaematopoieticcelltransplantimpactsurvivalforpatientswithearlystageleukaemiaormyelodysplasticsyndromeresearchincontext AT sharonasavage donortelomeresandtheirmagnitudeofshorteningpostallogeneichaematopoieticcelltransplantimpactsurvivalforpatientswithearlystageleukaemiaormyelodysplasticsyndromeresearchincontext AT stephaniejlee donortelomeresandtheirmagnitudeofshorteningpostallogeneichaematopoieticcelltransplantimpactsurvivalforpatientswithearlystageleukaemiaormyelodysplasticsyndromeresearchincontext AT johnelevine donortelomeresandtheirmagnitudeofshorteningpostallogeneichaematopoieticcelltransplantimpactsurvivalforpatientswithearlystageleukaemiaormyelodysplasticsyndromeresearchincontext AT waelsaber donortelomeresandtheirmagnitudeofshorteningpostallogeneichaematopoieticcelltransplantimpactsurvivalforpatientswithearlystageleukaemiaormyelodysplasticsyndromeresearchincontext AT abrahamaviv donortelomeresandtheirmagnitudeofshorteningpostallogeneichaematopoieticcelltransplantimpactsurvivalforpatientswithearlystageleukaemiaormyelodysplasticsyndromeresearchincontext |