Effect of Recipient Age and Stem Cell Source on the Association between Donor Telomere Length and Survival after Allogeneic Unrelated Hematopoietic Cell Transplantation for Severe Aplastic Anemia. Biol Blood Marrow Transplant 2016 Dec;22(12):2276-2282
Date
09/20/2016Pubmed ID
27641680Pubmed Central ID
PMC5116252DOI
10.1016/j.bbmt.2016.09.012Scopus ID
2-s2.0-85002614052 (requires institutional sign-in at Scopus site) 21 CitationsAbstract
We previously showed an association between donor leukocyte relative telomere length (RTL) and post-hematopoietic cell transplantation (HCT) survival in patients with severe aplastic anemia (SAA) who received bone marrow grafts at ages <40 years. Here, we tested the generalizability of the prior findings in an independent validation cohort and by recipient age and stem cell source in the combined discovery and validation cohorts. We used monoplex quantitative real-time PCR to measure RTL in: (1) a new SAA validation cohort of 428 patients (age range, .2 to 77 years) with available pretransplantation donor blood samples in the Center for International Blood and Marrow Transplant Research repository, and (2) 278 patients from the original cohort who had sufficient DNA to repeat RTL testing. We used Cox proportional hazard models to calculate hazard ratios (HRs), and 95% confidence intervals (CIs) across categories of donor RTL. Data from the validation cohort showed no association between donor RTL and patient survival, but further analysis identified differences by recipient age and stem cell source as the likely explanation. In patients <40 years, the HR comparing longest with shortest and middle RTL tertiles = .75; 95% CI, .44 to 1.30 versus HR = 1.05; 95% CI, .59 to 1.89 for patients ≥40 years, P interaction = .37. In bone marrow recipients, the HR = .68; 95% CI, .72 to 1.10 versus HR = 1.29; 95% CI, .64 to 2.62 for peripheral blood stem cell grafts; P interaction = .88. Analyses using data from the 2 cohorts showed a statistically significant survival benefit only in <40-year-old patients receiving bone marrow graft (HR comparing longest and middle RTL tertiles with shortest = .69; 95% CI, .50 to .95, P = .02). The study suggested that the association between donor RTL and post-HCT outcomes in recipients with SAA may vary by recipient age and stem cell source. A larger study is needed to account for multiple comparisons and to further test the generalizability of our findings.
Author List
Gadalla SM, Wang T, Dagnall C, Haagenson M, Spellman SR, Hicks B, Jones K, Katki HA, Lee SJ, 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
Age Factors
Aged
Anemia, Aplastic
Bone Marrow Transplantation
Child
Child, Preschool
Hematopoietic Stem Cell Transplantation
Humans
Infant
Middle Aged
Prognosis
Real-Time Polymerase Chain Reaction
Stem Cells
Survival
Telomere
Transplant Recipients
Unrelated Donors
Young Adult