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Donor Telomere Length and Causes of Death after Unrelated Hematopoietic Cell Transplant in Patients with Marrow Failure

Shahinaz M. Gadalla, Geraldine Aubert, Tao Wang, Michael Haagenson, Stephen R. Spellman, Lingxiao Wang, Hormuzd A. Katki, Sharon A. Savage and Stephanie J. Lee

Key points

  • Donor longer telomere length protects severe aplastic anemia transplant recipients from infection-related death.

Abstract

Previous studies suggest that longer donor leukocyte telomere length (TL) is associated with improved survival after hematopoietic cell transplant (HCT) in severe aplastic anemia (SAA). This study aimed to determine whether cell-specific lymphocyte TL are associated with certain post-HCT causes of death. We used flow cytometry and fluorescence in situ hybridization (flow FISH) to measure TL in donor total lymphocytes and subsets: naïve enriched T-cells (CD45RA+CD20-), memory enriched T-cells (CD45RA-CD20-), NK-fully differentiated T cells (CD45RA+CD57+), and B cells (CD45RA+CD20+). Competing risks 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 (CIBMTR) database and biorepository. The study included 197 patients who received unrelated donor HCT for SAA between 1988-2004. The median age at HCT was 15 years (range=0.5-40), and the median follow-up was 5 years (range <1 month - 20.7 years). Longer donor TL in all cell-subsets was associated with lower risk of all-cause mortality (p<0.01). In cause-specific mortality analyses, longer TL in B cells (HR=0.63, 95% CI=0.46-0.87, p=0.006), and possibly NK-fully differentiated T cells (HR=0.7, 95% CI=0.51-0.97, p=0.03) were associated with lower risk of infection-related death. Donor TL in other tested lymphocyte subsets were not statistically significantly associated with death from graft-versus-host disease or graft failure (p>0.05). Yet, a trend toward excess risk of graft-versus-host mortality was noted (HR-total lymphocyte TL=1.26, p=0.15). In conclusion, longer donor TL was associated with reduced infection-related deaths after HCT for SAA.

  • Submitted October 25, 2017.
  • Accepted April 4, 2018.