title: Association between donor leukocyte telomere length and survival after unrelated allogeneic hematopoietic cell transplantation for severe aplastic anemia.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
authors: Clinical Genetics Branch, National Cancer Institute, National Institutes of Health, Rockville, Maryland.
authors: Shahinaz M
authors: SM
authors: Gadalla
authors: Center for International Blood and Marrow Transplant hResearch and Division of Biostatistics, Medical College of Wisconsin, Milwaukee.
authors: Tao
authors: T
authors: Wang
authors: Center for International Blood and Marrow Transplant Research, Minneapolis, Minnesota.
authors: Michael
authors: M
authors: Haagenson
authors: Center for International Blood and Marrow Transplant Research, Minneapolis, Minnesota.
authors: Stephen R
authors: SR
authors: Spellman
authors: Center for International Blood and Marrow Transplant hResearch and Division of Biostatistics, Medical College of Wisconsin, Milwaukee4Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: Stephanie J
authors: SJ
authors: Lee
authors: Division of Blood and Marrow Transplantation, Center for Cancer and Blood Disorders, Children's National Medical Center, George Washington University Medical Center; Washington, DC6Experimental Transplantation and Immunology Branch, National Cancer Instit.
authors: Kirsten M
authors: KM
authors: Williams
authors: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts8Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, Massachusetts.
authors: Jason Y
authors: JY
authors: Wong
authors: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts8Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, Massachusetts.
authors: Immaculata
authors: I
authors: De Vivo
authors: Clinical Genetics Branch, National Cancer Institute, National Institutes of Health, Rockville, Maryland.
authors: Sharon A
authors: SA
authors: Savage
mesh_terms: D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000401:mortality / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D007962:Leukocytes / Q000648:ultrastructure*; D008297:Male; D008875:Middle Aged; D016615:Telomere / Q000648:ultrastructure*; D014019:Tissue Donors; D014184:Transplantation, Homologous; D055815:Young Adult