Donor telomere length and causes of death after unrelated hematopoietic cell transplantation in patients with marrow failure

Previous studies have suggested that longer donor leukocyte telomere length (TL) is associated with improved survival after hematopoietic cell transplantation (HCT) in severe aplastic anemia (SAA). This study aimed to determine whether cell-specific lymphocyte TL is associated with certain post-HCT causes of death. We used flow cytometry and fluorescence in situ hybridization to measure TL in donor total lymphocytes and subsets: naive enriched T cells (CD45RA(+)CD20(-)), memory enriched T cells (CD45RA(-)CD20(-)), natural killer (NK) fully differentiated T cells (CD45RA(+)CD57(+)), and B cells (CD45RA(+)CD20(+)). Competing risk survival regression was used for cause-specific death analyses. Clinical data and biospecimens were available from the Center for International Blood and Marrow Transplant Research database and biorepository. The study included 197 patients who underwent unrelated-donor HCT for SAA between 1988 and 2004. The median age at HCT was 15 years (range, 0.5-40 years), and the median follow-up was 5 years (range, < 1 month to 20.7 years). Longer donor TL in all cell subsets was associated with lower risk of all-cause mortality (P <.01). In cause-specific mortality analyses, longer TL in B cells (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.46-0.87; P=.006) and possibly NK fully differentiated T cells (HR, 0.7; 95% CI, 0.51 to 0.97; P=.03) was associated with lower risk of infection-related death. Donor TL in other tested lymphocyte subsets was not statistically significantly associated with death resulting from graft-versus-host disease or graft failure (P>.05). However, a trend toward excess risk of graft-versus-host mortality was noted (HR for total lymphocyte TL, 1.26; P=.15). In conclusion, longer donor TL was associated with reduced rate of infection-related deaths after HCT for SAA.