期刊
BLOOD
卷 136, 期 26, 页码 3070-3081出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood.2020005397
关键词
-
类别
资金
- Aplastic Anemia & MDS International Foundation
- National Institutes of Health, National Cancer Institute [K08CA204734, 5P30 CA006516, 5P30CA006516-54, 4U10HL069294]
- Jock and Bunny Adams Research and Education Endowment
- Jim and Lois Champy Fund
- Anna Fuller Fund
- Sigrid Juselius Foundation
- Maud Kuistila Memorial Foundation
- Vare Foundation for Pediatric Cancer Research
- Orion Research Foundation
- Public Health Service from the National Cancer Institute [5U24CA076518]
- National Heart, Lung and Blood Institute
- National Institute of Allergy and Infectious Diseases
- National Institutes of Health, National Heart, Lung and Blood Institute [4U10HL069294]
- Health Resources and Services Administration [HHSH250201200016C]
- Office of Naval Research [N00014-18-1-2850, N0014-19-1-2888]
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据