Gadalla Shahinaz M, Wang Tao, Haagenson Michael, Spellman Stephen R, Lee Stephanie J, Williams Kirsten M, Wong Jason Y, De Vivo Immaculata, Savage Sharon A
Clinical Genetics Branch, National Cancer Institute, National Institutes of Health, Rockville, Maryland.
Center for International Blood and Marrow Transplant hResearch and Division of Biostatistics, Medical College of Wisconsin, Milwaukee.
JAMA. 2015 Feb 10;313(6):594-602. doi: 10.1001/jama.2015.7.
Telomeres protect chromosome ends and are markers of cellular aging and replicative capacity.
To evaluate the association between recipient and donor pretransplant leukocyte telomere length with outcomes after unrelated donor allogeneic hematopoietic cell transplantation (HCT) for patients with severe aplastic anemia.
DESIGN, PARTICIPANTS, AND SETTING: The study included 330 patients (235 acquired, 85 Fanconi anemia, and 10 Diamond-Blackfan anemia) and their unrelated donors who had pre-HCT blood samples and clinical and outcome data available at the Center for International Blood and Marrow Transplant Research. Patients underwent HCT between 1989 and 2007 in 84 centers and were followed-up to March 2013.
Recipient and donor pre-HCT leukocyte telomere length classified into long (third tertile) and short (first and second tertiles combined) based on donor telomere length distribution.
Overall survival, neutrophil recovery, and acute and chronic graft-vs-host disease, as ascertained by transplant centers through regular patient follow-up.
Longer donor leukocyte telomere length was associated with higher survival probability (5-year overall survival, 56%; number at risk, 57; cumulative deaths, 50) than shorter donor leukocyte telomere length (5-year overall survival, 40%; number at risk, 71; cumulative deaths, 128; P = .009). The association remained statistically significant after adjusting for donor age, disease subtype, Karnofsky performance score, graft type, HLA matching, prior aplastic anemia therapy, race/ethnicity, and calendar year of transplant (hazard ratio [HR], 0.61; 95% CI, 0.44-0.86). Similar results were noted in analyses stratified on severe aplastic anemia subtype, recipient age, HLA matching, calendar year of transplant, and conditioning regimen. There was no association between donor telomere length and neutrophil engraftment at 28 days (cumulative incidence, 86% vs 85%; HR, 0.94; 95% CI, 0.73-1.22), acute graft-vs-host disease grades III-IV at 100 days (cumulative incidence, 22% vs 28%; HR, 0.77; 95% CI, 0.48-1.23), or chronic graft-vs-host disease at 1-year (cumulative incidence, 28% vs 30%; HR, 0.81; 95% CI, 0.53-1.24) for long vs short, respectively. Pretransplant leukocyte telomere length in the recipients was not associated with posttransplant survival (HR, 0.91; 95% CI, 0.64-1.30).
Longer donor leukocyte telomere length was associated with increased 5-year survival in patients who received HCT for severe aplastic anemia. Patient leukocyte telomere length was not associated with survival. The results of this observational study suggest that donor leukocyte telomere length may have a role in long-term posttransplant survival.
端粒保护染色体末端，是细胞衰老和复制能力的标志物。
评估严重再生障碍性贫血患者接受非亲缘供者异基因造血细胞移植（HCT）前受者和供者白细胞端粒长度与移植后结局之间的关联。
设计、参与者和研究地点：该研究纳入了330例患者（235例获得性再生障碍性贫血、85例范可尼贫血和10例先天性纯红细胞再生障碍性贫血）及其非亲缘供者，他们在国际血液和骨髓移植研究中心有HCT前血样以及临床和结局数据。患者于1989年至2007年在84个中心接受了HCT，并随访至2013年3月。
根据供者端粒长度分布，将受者和供者HCT前白细胞端粒长度分为长（第三三分位数）和短（第一和第二三分位数合并）。
通过移植中心定期随访确定的总生存、中性粒细胞恢复以及急性和慢性移植物抗宿主病。
供者白细胞端粒长度较长者的生存概率高于供者白细胞端粒长度较短者（5年总生存率，56%；风险数，57；累积死亡数，50）（5年总生存率，40%；风险数，71；累积死亡数，128；P = 0.009）。在调整供者年龄、疾病亚型、卡氏功能状态评分、移植物类型、HLA配型、既往再生障碍性贫血治疗、种族/民族和移植年份后，该关联仍具有统计学意义（风险比[HR]，0.61；95%可信区间[CI]，0.44 - 0.86）。在根据严重再生障碍性贫血亚型、受者年龄、HLA配型、移植年份和预处理方案分层的分析中也观察到了类似结果。供者端粒长度与28天时中性粒细胞植入无关（累积发生率，86%对85%；HR，0.94；95%CI，0.73 - 1.22），与100天时急性移植物抗宿主病III - IV级无关（累积发生率，22%对28%；HR，0.77；95%CI，0.48 - 1.23），也与1年时慢性移植物抗宿主病无关（累积发生率，28%对30%；HR，0.81；95%CI，0.53 - 1.24），长端粒和短端粒分别对应上述情况。受者移植前白细胞端粒长度与移植后生存无关（HR，0.91；95%CI，0.64 - 1.30）。
供者白细胞端粒长度较长与严重再生障碍性贫血患者接受HCT后的5年生存率增加相关。患者白细胞端粒长度与生存无关。这项观察性研究的结果表明，供者白细胞端粒长度可能在移植后长期生存中起作用。
