title: Age-adjusted recipient pretransplantation telomere length and treatment-related mortality after hematopoietic stem cell transplantation.
abstract: Telomere attrition induces cell senescence and apoptosis. We hypothesized that age-adjusted pretransplantation telomere length might predict treatment-related mortality (TRM) after hematopoietic stem cell transplantation (HSCT). Between 2000 and 2005, 178 consecutive patients underwent HSCT from HLA-identical sibling donors after myeloablative conditioning regimens, mainly for hematologic malignancies (n = 153). Blood lymphocytes' telomere length was measured by real-time quantitative PCR before HSCT. Age-adjusted pretransplantation telomere lengths were analyzed for correlation with clinical outcomes. After age adjustment, patients' telomere-length distribution was similar among all 4 quartiles except for disease stage. There was no correlation between telomere length and engraftment, GVHD, or relapse. The overall survival was 62% at 5 years (95% confidence interval [CI], 54-70). After a median follow-up of 51 months (range, 1-121 months), 43 patients died because of TRM. The TRM rate inversely correlated with telomere length. TRM in patients in the first (lowest telomere length) quartile was significantly higher than in patients with longer telomeres (P = .017). In multivariate analysis, recipients' age (hazard ratio, 1.1; 95% CI, .0-1.1; P = .0001) and age-adjusted telomere length (hazard ratio, 0.4; 95% CI; 0.2-0.8; P = .01) were independently associated with TRM. In conclusion, age-adjusted recipients' telomere length is an independent biologic marker of TRM after HSCT.
authors.affiliation: Service d'Hématologie Greffe, Assistance Publique-Hôpitaux de Paris, Hôpital Saint Louis, France. regis.peffaultdelatour@sls.aphp.fr
authors.forename: Régis
authors.initials: R
authors.lastname: Peffault de Latour
authors.forename: Rodrigo T
authors.initials: RT
authors.lastname: Calado
authors.forename: Marc
authors.initials: M
authors.lastname: Busson
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Abrams
authors.forename: Nadir
authors.initials: N
authors.lastname: Adoui
authors.forename: Marie
authors.initials: M
authors.lastname: Robin
authors.forename: Jérôme
authors.initials: J
authors.lastname: Larghero
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dhedin
authors.forename: Alienor
authors.initials: A
authors.lastname: Xhaard
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Clave
authors.forename: Dominique
authors.initials: D
authors.lastname: Charron
authors.forename: Antoine
authors.initials: A
authors.lastname: Toubert
authors.forename: Pascale
authors.initials: P
authors.lastname: Loiseau
authors.forename: Gérard
authors.initials: G
authors.lastname: Socié
authors.forename: Neal S
authors.initials: NS
authors.lastname: Young
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000401:mortality; D006680:HLA Antigens / Q000378:metabolism; D019337:Hematologic Neoplasms / Q000235:genetics / Q000401:mortality* / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality; D035781:Siblings; D015996:Survival Rate; D059505:Telomere Homeostasis; D019172:Transplantation Conditioning / Q000401:mortality*; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D006680:HLA Antigens