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Relative Telomere Length Prior to Hematopoietic Cell Transplantation (HCT) and Outcome after Unrelated Donor HCT for Acute Leukemia.

Research paper by Youjin Y Wang, Tao T Wang, Casey C Dagnall, Michael M Haagenson, Stephen R SR Spellman, Belynda B Hicks, Kristine K Jones, Stephanie J SJ Lee, Sharon A SA Savage, Shahinaz M SM Gadalla

Indexed on: 09 Apr '17Published on: 09 Apr '17Published in: Biology of Blood and Marrow Transplantation



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 (CIBMTR), we randomly selected 536 acute leukemia (AL) 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. RTL was measured by real time qPCR. 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 AML and 140 ALL patients. Median age at HCT=41 years, range 0.5-66 years, and median follow-up for survivors=5.1 years (range= 0.4-8.3). Significant inverse correlations between age and RTL were observed in patients with AML (r=-0.44, p<0.0001), and ALL (r=-0.48 p<0.0001). Patients with ALL had longer RTL than those with AML (mean T/S= 0.48 vs. 0.43, respectively); the difference was not statistically significant after adjusting for patient age (p=0.96). Pre-HCT RTL in AL patients was not statistically significantly associated with overall survival (HR for longest RTL compared with shortest=0.91, 95% CI=0.65-1.28), disease free survival (HR=0.90, 95% CI=0.64-1.25), transplant related mortality (HR=0.97, 95% CI=0.60-1.59), incidence of relapse (HR=0.89, 95% CI=0.56-1.40), neutrophil engraftment (HR=1.06, 95% CI=0.85-1.32), or acute (HR=1.11, 95% CI=0.81-1.53 for grade II-IV, HR=0.92, 95% CI=0.54-1.59 for grade III-IV) and chronic graft-versus-host disease (HR=1.10, 95% CI=0.81-1.50). In this study, recipient pre-HCT RTL had no prognostic role in post-transplant outcomes in AL patients.

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