Association between donor leukocyte telomere length and survival after unrelated allogeneic hematopoietic cell transplantation for severe aplastic anemia.
Association between donor leukocyte telomere length and survival after unrelated allogeneic hematopoietic cell transplantation for severe aplastic anemia.
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DOI：
10.1001/jama.2015.7
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发表时间：
2015-02-10
影响因子：
120.7
通讯作者：
Savage, Sharon A.
中科院分区：
文献类型：
--
作者：
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.
端粒保护染色体末端，是细胞衰老和复制能力的标志。为了评估受者和供者移植前白细胞端粒长度与非血缘异基因造血细胞移植(HCT)治疗重型再生障碍性贫血(HCT)患者预后的关系，该研究包括330名患者(235例获得性、85例Fanconi贫血和10例Diamond Blackfan贫血)及其非血缘供者，他们在HCT前采集了血样，并获得了国际血液和骨髓移植研究中心提供的临床和预后数据。从1989年到2007年，84个中心的患者接受了HCT，并进行了随访，直到2013年3月，根据供者端粒长度的分布，将受者和供者的HCT前白细胞端粒长度分为长的(第三个三分位数)和短的(第一个和第二个三分位数之和)。移植中心通过定期患者随访确定的总存活率、中性粒细胞恢复以及急性和慢性移植物抗宿主病(GvHD)。较长的供者白细胞端粒长度与较高的生存概率相关(5年总生存率=56%(风险数=57，累积死亡=50比40%(风险数=71；累积死亡=128)，分别为长与短；p=0.009)。在调整了供者年龄、疾病亚型、卡诺夫斯基评分、移植物类型、人类白细胞抗原配型、既往再生障碍性贫血治疗、种族和移植历年(风险比(HR)=0.61，95%可信区间=0.44-0.86)后，这种相关性仍然具有统计学意义。在对严重再生障碍性贫血亚型、受者年龄、人类白细胞抗原配型、移植历年和调理方案进行分层的分析中也发现了类似的结果。供者端粒长度与移植后28天的中性粒细胞植入(累积发生率分别为86%和85%；HR=0.94，95%CI=0.73~1.22)、100天的急性GvHD III~IV级(累积发生率=22%和28%；HR=0.77，95%CI=0.48~1.23)和1年的慢性GvHD(累积发生率分别为28%和30%；HR=0.81，95%CI=0.53~1.24)无关。受者移植前白细胞端粒长度与移植后生存率无关(HR=0.91，95%CI=0.64~1.30)。在因严重再生障碍性贫血接受HCT治疗的患者中，供者白细胞端粒长度较长与5年生存率增加相关。患者的白细胞端粒长度与存活率无关。这项观察性研究的结果表明，供者的白细胞端粒长度可能在移植后的长期存活中起作用。
Telomeres protect chromosome ends and are markers of cellular aging and replicative capacity. To evaluate the association between recipient and donor pre-transplant leukocyte telomere length with outcomes after unrelated donor allogeneic hematopoietic cell transplantation (HCT) for patients with severe aplastic anemia 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 until March 2013 Recipient and donor pre-HCT leukocyte telomere length classified into long (3rd tertile) and short (1st and 2nd tertiles combined) based on donor telomere length distribution. Overall survival, neutrophil recovery, and acute and chronic graft-versus-host disease (GvHD), 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 vs. 40% (number at risk =71; cumulative deaths=128), in the long vs. short, respectively; p=0.009). The association remained statistically significant after adjusting for donor age, disease subtype, Karnofsky performance score, graft type, HLA matching, prior aplastic anemia therapy, race, and calendar year of transplant (hazard ratio (HR)= 0.61, 95% confidence intervals=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 GvHD grades III–IV at 100 days (cumulative incidence =22% vs. 28%; HR=0.77, 95% CI= 0.48–1.23), or chronic GvHD at 1-year (cumulative incidence =28% vs. 30%; HR=0.81, 95% CI= 0.53–1.24) for long versus short respectively. Pre-transplant leukocyte telomere length in the recipients was not associated with post-transplant 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 post-transplant survival.
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DOI：
10.1016/j.mrfmmm.2011.04.003
发表时间：
2012-02-01
影响因子：
2.3
作者：
Aubert, Geraldine;Hills, Mark;Lansdorp, Peter M.
通讯作者：
Lansdorp, Peter M.
影响因子：
4.5
作者：
Aubert G;Baerlocher GM;Vulto I;Poon SS;Lansdorp PM
通讯作者：
Lansdorp PM
影响因子：
14.9
作者：
Cawthon RM
通讯作者：
Cawthon RM
影响因子：
4.3
作者：
Bacigalupo, Andrea;Ballen, Karen;Rizzo, Doug;Giralt, Sergio;Lazarus, Hillard;Ho, Vincent;Apperley, Jane;Slavin, Shimon;Pasquini, Marcelo;Sandmaier, Brenda M.;Barrett, John;Blaise, Didier;Lowski, Robert;Horowitz, Mary
通讯作者：
Horowitz, Mary
影响因子：
20.3
作者：
Deeg, H. Joachim;O'Donnell, Margaret;Storer, Barry
通讯作者：
Storer, Barry