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Longer donor leukocyte telomere reduces infection-related mortality in aplastic anemia
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Longer donor leukocyte telomere length appeared associated with reduced infection-related mortality among patients with severe aplastic anemia who underwent hematopoietic stem cell transplantation, according to study results.
Previous research suggested longer donor leukocyte telomere is associated with improved survival after HSCT in severe aplastic anemia.
Shahinaz M. Gadalla, MD, PhD, Earl Stadtman investigator in the division of cancer epidemiology and genetics at NCI, and colleagues assessed whether cell-specific lymphocyte telomere length was associated with certain causes of death after HSCT.
Gadalla and colleagues evaluated data and biospecimens from 217 patients in the Center for International Blood and Marrow Transplant Research database and biorepository.
All patients underwent HSCT with unrelated donors for severe aplastic anemia between 1988 and 2004.
Researchers used flow cytometry and fluorescence in situ hybridization to measure telomere length in donor total lymphocytes and the following subsets: naive enriched T-cells, memory enriched T-cells, fully differentiated natural killer T cells, and B cells.
Researchers also investigated the impact of donor cell-specific lymphocyte telomere length on infections, graft-versus-host disease and graft failure, the primary causes of mortality after HSCT.
The final analysis included 197 patients (54.7% male). The majority (67.5%) of patients had acquired severe aplastic anemia, 28.9% had Fanconi anemia and 3.6% had Diamond-Blackfan anemia.
Median age at HSCT was 15 years (range, 0.5-40). Median follow-up was 5 years (range, < 1 month to 20.7 months).
Median donor total lymphocyte telomere length was 7.1 kb (range, 3.7-11.2). Among the subsets, telomere length appeared longest in B cells (median, 8.2 kb; range, 5.4-11.5) and shortest in fully differentiated natural killer T cells (median, 6.1 kb; range, 3.3-10.1).
Leukocyte telomere length appeared highly correlated with naive (r = 0.92) and memory T-cell telomere lengths (r = 0.93; P < .001).
Researchers observed a modest correlation between leukocyte telomere length and telomere lengths of B cells (r = 0.77) and natural killer cells (r = 0.79; P < .001).
Longer donor telomere length in all cell subsets appeared associated with reduced risk for all-cause mortality (P < .01).
Multivariate cause-specific mortality analyses showed longer telomere length in B cells (HR = 0.63; 95% CI, 0.46-0.87), and possibly fully differentiated natural killer T cells (HR = 0.7; 95% CI, 0.51-0.97), reduced risk for infection-related mortality.
The donor telomere length for other subsets did not appear significantly associated with mortality related to GVHD or graft failure; however, they noted a trend toward excess risk for GVHD mortality (HR for total lymphocyte telomere length =1.26).
“A prospective, larger study is needed to validate these findings in the light of the recent improvement in [HSCT] outcomes for patients with severe aplastic anemia,” the researchers wrote. – by Melinda Stevens
Disclosures: Gadalla reports no relevant financial disclosures. One author reports part-time employment with Repeat Diagnostics Inc.
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