Impact of donor telomere length on survival in patients undergoing matched sibling donor transplantation for aplastic anaemia

医学 四分位数 氟达拉滨 危险系数 内科学 移植 端粒 环磷酰胺 外科 免疫学 移植物抗宿主病 胃肠病学 化疗 置信区间 生物 DNA 遗传学
作者
Aruna Barade,Fouzia N. Aboobacker,Anu Korula,Kavitha M. Lakshmi,Anup J. Devasia,Aby Abraham,Vikram Mathews,Eunice Sindhuvi Edison,Biju George
出处
期刊:British Journal of Haematology [Wiley]
卷期号:196 (3): 724-734 被引量:7
标识
DOI:10.1111/bjh.17880
摘要

Summary Although telomere shortening is seen frequently in patients with aplastic anaemia (AA), there are no data on its association in matched sibling donor (MSD) transplants. We evaluated the effect of pre‐transplant telomere length of patients and donors, measured by quantitative real‐time polymerase chain reaction in 163 recipients undergoing MSD transplants. The median age of patients and donors was 24 and 26 years, respectively. Fludarabine and cyclophosphamide was the main conditioning regimen used and all received peripheral blood stem cell grafts. Engraftment occurred in 89% with graft failure (primary and secondary) in 6%. Acute and chronic graft‐ versus ‐host disease (GVHD) occurred in 28% and 24%, respectively. At a median follow‐up of 37 months, 117 patients (72%) were alive. All patients and donors were divided into short and long telomere length based on their median and quartile values. Patient telomere length was not associated with severity of AA, neutrophil recovery, graft failure, acute GVHD or chronic GVHD. Longer donor telomere length was associated with better overall survival [hazard ratio (HR) = 0·2, P = 0·006] but did not influence neutrophil recovery, graft failure, acute or chronic GVHD. The five‐year overall survival was significantly better (94·9 ± 3·5% vs 65·4 ± 4·3%, P = 0·002) for donors with long (highest quartile, DTL‐HQ) versus short (lower three quartiles, DTL‐LQ) telomeres, respectively. On multivariate analysis, longer donor telomere length, recipient age and acute GVHD continued to remain significant. This is the first study demonstrating an association of donor telomere length on overall survival following MSD transplant for AA but it needs to be confirmed in larger studies.
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