Faculty Collaboration Database

No association between donor telomere length and outcomes after allogeneic unrelated hematopoietic cell transplant in patients with acute leukemia. Bone Marrow Transplant 2018 Apr;53(4):383-391

Date

12/23/2017

Pubmed ID

29269807

Pubmed Central ID

PMC5898974

DOI

10.1038/s41409-017-0029-9

Scopus ID

2-s2.0-85038620776 (requires institutional sign-in at Scopus site)   10 Citations

Abstract

Recent studies suggest improved survival in patients with severe aplastic anemia receiving hematopoietic cell transplant (HCT) from unrelated donors with longer telomeres. Here, we tested whether this effect is generalizable to patients with acute leukemia. From the Center for International Blood and Marrow Transplant Research (CIBMTR^®) database, we identified 1097 patients who received 8/8 HLA-matched unrelated HCT for acute myeloid leukemia (AML) or acute lymphocytic leukemia (ALL) between 2004 and 2012 with myeloablative conditioning, and had pre-HCT blood sample from the donor in CIBMTR repository. The median age at HCT for recipients was 40 years (range ≤1-68), and 32 years for donors (range = 18-61). We used qPCR for relative telomere length (RTL) measurement, and Cox proportional hazard models for statistical analyses. In a discovery cohort of 300 patients, longer donor RTL (>25th percentile) was associated with reduced risks of relapse (HR = 0.62, p = 0.05) and acute graft-versus-host disease II-IV (HR = 0.68, p = 0.05), and possibly with a higher probability of neutrophil engraftment (HR = 1.3, p = 0.06). However, these results did not replicate in two validation cohorts of 297 and 488 recipients. There was one exception; a higher probability of neutrophil engraftment was observed in one validation cohort (HR = 1.24, p = 0.05). In a combined analysis of the three cohorts, no statistically significant associations (all p > 0.1) were found between donor RTL and any outcomes.

Author List

Gadalla SM, Wang T, Loftus D, Friedman L, Dagnall C, Haagenson M, Spellman SR, Buturovic L, Blauwkamp M, Shelton J, Fleischhauer K, Hsu KC, Verneris MR, Krstajic D, Hicks B, Jones K, Lee SJ, Savage SA

Author

Tao Wang PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acute Disease
Adolescent
Adult
Aged
Child
Child, Preschool
Female
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Humans
Infant
Infant, Newborn
Leukemia
Leukemia, Myeloid, Acute
Male
Middle Aged
Neutrophils
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Prognosis
Recurrence
Telomere Homeostasis
Transplantation, Homologous
Treatment Outcome
Unrelated Donors
Young Adult