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. 2018 May 24;131(21):2393-2398.
doi: 10.1182/blood-2017-10-812735. Epub 2018 Apr 9.

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

Shahinaz M Gadalla  1 , Geraldine Aubert  2   3 , Tao Wang  4   5 , Michael Haagenson  6 , Stephen R Spellman  6 , Lingxiao Wang  7   8 , Hormuzd A Katki  7 , Sharon A Savage  1 , Stephanie J Lee  5   9
Affiliations

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

Shahinaz M Gadalla et al. Blood. .

Abstract

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: naïve 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.

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Conflict of interest statement

Conflict-of-interest disclosure: G.A. holds part-time employment with Repeat Diagnostics Inc., a company specializing in clinical telomere length measurements. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Scatter plots of donor flow FISH lymphocyte TL represented on age-matched control curves. Lines represents the first, 10th, 50th, 90th, and 99th percentiles of TL for ages 0 to 100 years constructed from 400 healthy individuals.
Figure 2.
Figure 2.
Cumulative incidence of posttransplantation infection-related death in patients with SAA by donor B-cell TL.
See this image and copyright information in PMC

References

    1. Young NS. Current concepts in the pathophysiology and treatment of aplastic anemia. Hematology Am Soc Hematol Educ Program. 2013;2013:76-81. - PMC - PubMed
    1. Wegman-Ostrosky T, Savage SA. The genomics of inherited bone marrow failure: from mechanism to the clinic. Br J Haematol. 2017;177(4):526-542. - PubMed
    1. Baerlocher GM, Lansdorp PM. Telomere length measurements using fluorescence in situ hybridization and flow cytometry. Methods Cell Biol. 2004;75:719-750. - PubMed
    1. Maury S, Balère-Appert ML, Chir Z, et al. ; French Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC). Unrelated stem cell transplantation for severe acquired aplastic anemia: improved outcome in the era of high-resolution HLA matching between donor and recipient. Haematologica. 2007;92(5):589-596. - PubMed
    1. Chu R, Brazauskas R, Kan F, et al. Comparison of outcomes after transplantation of G-CSF-stimulated bone marrow grafts versus bone marrow or peripheral blood grafts from HLA-matched sibling donors for patients with severe aplastic anemia. Biol Blood Marrow Transplant. 2011;17(7):1018-1024. - PMC - PubMed

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