Short telomere length predicts nonrelapse mortality after stem cell transplantation for myelodysplastic syndrome.
Journal
Blood
ISSN: 1528-0020
Titre abrégé: Blood
Pays: United States
ID NLM: 7603509
Informations de publication
Date de publication:
24 12 2020
24 12 2020
Historique:
received:
18
02
2020
accepted:
30
07
2020
entrez:
28
12
2020
pubmed:
29
12
2020
medline:
7
4
2021
Statut:
ppublish
Résumé
Allogeneic hematopoietic stem cell transplantation is the only potentially curative treatment for patients with myelodysplastic syndrome (MDS), but long-term survival is limited by the risk of transplant-related complications. Short telomere length, mediated by inherited or acquired factors, impairs cellular response to genotoxic and replicative stress and could identify patients at higher risk for toxicity after transplantation. We measured relative telomere length in pretransplant recipient blood samples in 1514 MDS patients and evaluated the association of telomere length with MDS disease characteristics and transplantation outcomes. Shorter telomere length was significantly associated with older age, male sex, somatic mutations that impair the DNA damage response, and more severe pretransplant cytopenias, but not with bone marrow blast count, MDS treatment history, or history of prior cancer therapy. Among 1267 patients ≥40 years old, telomere length in the shortest quartile was associated with inferior survival (P < .001) because of a high risk of nonrelapse mortality (NRM; P = .001) after adjusting for significant clinical and genetic variables. The adverse impact of shorter telomeres on NRM was independent of recipient comorbidities and was observed selectively among patients receiving more intensive conditioning, including myeloablative regimens and higher dose melphalan-based reduced-intensity regimens. The effect of shorter telomeres on NRM was prominent among patients who developed severe acute graft-versus-host disease, suggesting that short telomere length may limit regenerative potential of mucosal tissues after acute injury. MDS patients with shorter telomere length, who have inferior survival driven by excess toxicity, could be considered for strategies focused on minimizing toxic effects of transplantation.
Identifiants
pubmed: 33367544
pii: S0006-4971(20)83914-7
doi: 10.1182/blood.2020005397
pmc: PMC7770569
doi:
Substances chimiques
Melphalan
Q41OR9510P
Types de publication
Clinical Trial
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
3070-3081Subventions
Organisme : NHLBI NIH HHS
ID : U10 HL069294
Pays : United States
Organisme : NCI NIH HHS
ID : K08 CA204734
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA076518
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL116324
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA006516
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2020 by The American Society of Hematology.
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