Relative Telomere Length before Hematopoietic Cell Transplantation and Outcome after Unrelated Donor Hematopoietic Cell Transplantation for Acute Leukemia

Abstract

Telomeres are tandem nucleotide repeats and a protein complex located at the end of the chromosomes maintaining genomic stability. Their potential as a predictive biomarker for outcomes after allogeneic hematopoietic cell transplant (HCT) in hematologic malignancies is still unclear. From the Center for International Blood and Marrow Transplant Research we randomly selected 536 acute leukemia patients from those who underwent myeloablative 8/8 HLA-matched unrelated donor HCT between 2005 and 2012 and who had an available pre-HCT blood sample in the repository. Relative telomere length (RTL) was measured by real-time quantitative PCR. We used Kaplan-Meier and competing risk estimators to calculate survival probability and cumulative incidence, respectively, across patient RTL tertiles. Cox proportional hazard regression was used for adjusted analyses. The study included 396 acute myeloid leukemia (AML) and 140 acute lymphoblastic leukemia (ALL) patients. Median age at HCT was 41 years (range, .5 to 66), and median follow-up for survivors was 5.1 years (range, .4 to 8.3). Significant inverse correlations between age and RTL were observed in patients with AML (r = –.44, P < .0001) and ALL (r = –.48, P < .0001). Patients with ALL had longer RTL than those with AML (.48 versus .43, respectively); the difference was not statistically significant after adjusting for patient age (P = .96). Pre-HCT RTL in acute leukemia patients was not statistically significantly associated with overall survival (HR for longest RTL compared with shortest, .91; 95% CI, .65 to 1.28), disease-free survival (HR, .90; 95% CI, .64 to 1.25), transplant-related mortality (HR, .97; 95% CI, .60 to 1.59), incidence of relapse (HR, .89; 95% CI, .56 to 1.40), neutrophil engraftment (HR, 1.06; 95% CI, .85 to 1.32), or grades II to IV acute graft-versus-host disease (HR, 1.11; 95% CI, .81 to 1.53), grades III-IV acute graft-versus-host disease (HR, .92; 95% CI, .54 to 1.59), and chronic graft-versus-host disease (HR, 1.10; 95% CI, .81 to 1.50). In this study, recipient pre-HCT RTL had no prognostic role in post-transplant outcomes in acute leukemia patients.