Association between donor leukocyte telomere length and survival after unrelated allogeneic hematopoietic cell transplantation for severe aplastic anemia. JAMA 2015 Feb 10;313(6):594-602
Date
02/11/2015Pubmed ID
25668263Pubmed Central ID
PMC4388056DOI
10.1001/jama.2015.7Scopus ID
2-s2.0-84922553097 (requires institutional sign-in at Scopus site) 70 CitationsAbstract
IMPORTANCE: Telomeres protect chromosome ends and are markers of cellular aging and replicative capacity.
OBJECTIVE: To evaluate the association between recipient and donor pretransplant leukocyte telomere length with outcomes after unrelated donor allogeneic hematopoietic cell transplantation (HCT) for patients with severe aplastic anemia.
DESIGN, PARTICIPANTS, AND SETTING: The study included 330 patients (235 acquired, 85 Fanconi anemia, and 10 Diamond-Blackfan anemia) and their unrelated donors who had pre-HCT blood samples and clinical and outcome data available at the Center for International Blood and Marrow Transplant Research. Patients underwent HCT between 1989 and 2007 in 84 centers and were followed-up to March 2013.
EXPOSURES: Recipient and donor pre-HCT leukocyte telomere length classified into long (third tertile) and short (first and second tertiles combined) based on donor telomere length distribution.
MAIN OUTCOMES AND MEASURES: Overall survival, neutrophil recovery, and acute and chronic graft-vs-host disease, as ascertained by transplant centers through regular patient follow-up.
RESULTS: Longer donor leukocyte telomere length was associated with higher survival probability (5-year overall survival, 56%; number at risk, 57; cumulative deaths, 50) than shorter donor leukocyte telomere length (5-year overall survival, 40%; number at risk, 71; cumulative deaths, 128; P = .009). The association remained statistically significant after adjusting for donor age, disease subtype, Karnofsky performance score, graft type, HLA matching, prior aplastic anemia therapy, race/ethnicity, and calendar year of transplant (hazard ratio [HR], 0.61; 95% CI, 0.44-0.86). Similar results were noted in analyses stratified on severe aplastic anemia subtype, recipient age, HLA matching, calendar year of transplant, and conditioning regimen. There was no association between donor telomere length and neutrophil engraftment at 28 days (cumulative incidence, 86% vs 85%; HR, 0.94; 95% CI, 0.73-1.22), acute graft-vs-host disease grades III-IV at 100 days (cumulative incidence, 22% vs 28%; HR, 0.77; 95% CI, 0.48-1.23), or chronic graft-vs-host disease at 1-year (cumulative incidence, 28% vs 30%; HR, 0.81; 95% CI, 0.53-1.24) for long vs short, respectively. Pretransplant leukocyte telomere length in the recipients was not associated with posttransplant survival (HR, 0.91; 95% CI, 0.64-1.30).
CONCLUSIONS AND RELEVANCE: Longer donor leukocyte telomere length was associated with increased 5-year survival in patients who received HCT for severe aplastic anemia. Patient leukocyte telomere length was not associated with survival. The results of this observational study suggest that donor leukocyte telomere length may have a role in long-term posttransplant survival.
Author List
Gadalla SM, Wang T, Haagenson M, Spellman SR, Lee SJ, Williams KM, Wong JY, De Vivo I, Savage SAAuthor
Tao Wang PhD Associate Professor in the Institute for Health and Equity department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Anemia, Aplastic
Child
Child, Preschool
Female
Hematopoietic Stem Cell Transplantation
Humans
Infant
Kaplan-Meier Estimate
Leukocytes
Male
Middle Aged
Telomere
Tissue Donors
Transplantation, Homologous
Young Adult
