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Donor leukocyte telomere length linked to transplantation outcomes in aplastic anemia
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Longer donor leukocyte telomere length was associated with improved survival in patients with severe aplastic anemia who underwent allogeneic hematopoietic stem cell transplantation, according to study results.
Shahinaz M. Gadalla, MD, PhD, of the clinical genetics branch at the NCI, and colleagues evaluated data from 330 patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) with unrelated donors between 1989 and 2007. The majority (71%) of patients had acquired severe aplastic anemia, 26% had Fanconi anemia and 3% had Diamond-Blackfan anemia.
The median age of patients at the time of transplantation was 15 years (range, 0.5-39) and 71% were non-Hispanic white. The median age of the donors was 36 years (range, 19-57).
Leukocyte telomere length was inversely correlated with age in donors and recipients (P ˂ .001 for both). However, patients with severe aplastic anemia had significantly shorter leukocyte telomere length than their donors, even after adjustments for age (P ˂ .001).
Researchers divided donor telomere length into tertiles. Fewer patients with donors with the shortest leukocyte telomere length achieved 1-year OS post-HSCT (46%; 95% CI, 37-56) than did patients whose donors were in the intermediate tertile (53%; 95% CI, 43-62) and longest tertile (61%; 95% CI, 52-70; P = .09).
Five-year survival probabilities also were significantly greater in patients with donors in the longest vs. shortest tertile of leukocyte telomere length (56% vs. 40%; P = .009).
The association between longer donor leukocyte telomere length and survival persisted in analyses adjusted for donor age, disease subtype, Karnofsky performance score, graft type, HLA matching, prior aplastic anemia therapy, race/ethnicity and year of transplant (HR = 0.61; 95% CI, 0.44-0.86).
However, patients’ leukocyte telomere lengths before transplantation were not associated with post-transplant survival (HR = 0.91; 95% CI, 0.64-1.3).
Neutrophil engraftment at 28 days was not statistically associated with longer donor leukocyte telomere length (HR = 0.94; 95% CI, 0.73-1.22). Further, a similar proportion of patients with long vs. short donor leukocyte telomere length experienced grade 3 to 4 acute graft-versus-host disease (GVHD) at 100 days (22% vs. 28%; HR = 0.77; 95% CI, 0.48-1.23) and chronic GVHD at 1 year (28% vs. 30%; HR = 0.81; 95% CI, 0.53-1.24).
“Although survival after HSCT has improved over the last decade, the survival outcomes of unrelated donor transplants for severe aplastic anemia are still unsatisfactory with a 5-year survival probability of 39% to 62%,” Gadalla and colleagues wrote. “This observational study suggests that donor leukocyte telomere length may have a role in long-term post-transplant survival.”
Because there was no association between longer donor leukocyte telomere length and engraftment, additional work is necessary to evaluate the link between leukocyte telomere length and survival, Ayman Saad, MD, Shin Mineishi, MD, and Racquel Innis-Shelton, MD, all of the Blood and Marrow Transplantation & Cell Therapy Program at the University of Alabama, Birmingham, wrote in an accompanying editorial.
“It then stands to reason that the difference must be due to transplant-related mortality, although the authors did not find any relationship between donor leukocyte telomere length and specific causes of death in this study,” Saad, Mineishi and Innis-Shelton wrote. “Were there less infections or less regimen-related toxicities? If there were fewer infections, is longer leukocyte telomere length associated with more rapid immune reconstitution? Further data are needed to clarify these issues. This observational report by Gadalla et al provides potentially important data and may mark the beginning of other new findings to come.” – by Alexandra Todak
Disclosure: The researchers report no relevant financial disclosures.
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