Indexed on: 20 Sep '16Published on: 20 Sep '16Published in: Biology of Blood and Marrow Transplantation
We previously showed an association between donor leukocyte relative telomere length (RTL) and post-hematopoietic cell transplant (HCT) survival in severe aplastic anemia (SAA) patients who received bone marrow grafts at age <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 qPCR to measure RTL in: 1) a new SAA validation cohort of 428 patients (age range 0.2-77 years) with available pre-transplant donor blood samples in the Center for International Blood and Marrow Transplant Research (CIBMTR) Research Repository, and 2) 278 patients from the original cohort who had sufficient DNA to repeat RTL. 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=0.75, 95% CI=0.44-1.30 vs. HR=1.05, 95%CI=0.59-1.89 for patients ≥40 years, p-interaction=0.37). In bone marrow recipients, the HR=0.68, 95% CI=0.72-1.10 vs. HR= 1.29, 95% CI=0.64-2.62 for peripheral blood stem cell grafts, p-interaction=0.88). Analyses using data from the two 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 =0.69, 95% CI=0.50-0.95, p=0.02). 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.