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【资讯翻译】Longer Donor Telomeres May Confer Survival After Cell Trans...

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发表于 2015-2-27 15:22:37 | 显示全部楼层 |阅读模式
Longer Donor Telomeres May Confer Survival After Cell Transplant

Longer donor leukocyte telomeres may mean longer survival for aplastic anemia patients who undergo hematopoeitic cell transplantation (HCT), new findings show.

Telomeres are sections of noncoding, repeating DNA that protect chromosome ends. Their length shortens with each cell division, Dr. Shahinaz Gadalla, of the National Cancer Institute in Rockville, Maryland, and her colleagues explain in their report, published online February 10 in JAMA. "Consequently, telomeres are markers of cellular replicative capacity, cellular senescence, and aging," they write.

When patients undergo HCT for aplastic anemia, the researchers add, transplanted donor cells must replicate and expand rapidly for successful engraftment, and studies have found that shortening of telomeres in donor cells is accelerated after transplant.

To investigate whether relative leukocyte telomere length in recipients before HCT and in donors might be related to outcomes, the researchers looked at 330 patients who underwent HCT from an unrelated donor at 84 different centers, using data from the Center for International Blood and Marrow Transplant Research. Patients were treated between 1989 and 2007, and followed up through March 2013.

Donor and recipient telomere length were classified as long (in the third tertile, n=113) or short (first and second tertiles combined, n=217).

Five-year survival came to 56% for patients who received transplants from donors with long telomeres versus 40% for patients whose donors had short telomeres (p=.009). One-year survival came to 60% with a long-telomere donor and 50% with a short telomere donor, while three-year survival came to 58% vs. 44%, respectively.

The relationship remained statistically significant after the investigators adjusted for donor age and several other factors, for a hazard ratio of 0.61. Results were also similar when the researchers analyzed the results based on severe aplastic anemia subtype, recipient age, human leukocyte antigen matching, year of transplant and conditioning regimen.

However, the researchers found no relationship between donors' telomere length and neutrophil engraftment at 28 days or graft vs. host disease at 100 days or one year. Recipients' pre-transplant leukocyte telomere length was also not related to their survival after transplant.

"Our study has shown that longer donor telomere length is associated with higher survival probability after unrelated hematopoietic cell transplant for patients with severe aplastic anemia," Dr. Gadalla told Reuters Health via E-mail. "The study is the first to show that donor telomere length may play a role in outcomes after hematopoietic cell transplant. A replication study in a large number of patients is required before moving this observation to clinical application."

She added: "At this stage, it is still too early to recommend adding telomere length measurement as a donor-selection criterion. We still have more work to do, including but not limited to identifying the best method to measure telomere length in donors, and identifying the patient population who will benefit the most from donors with longer telomeres."

The mechanism behind recipients' better survival with longer donor telomeres is not clear, given that it is not associated with engraftment status, Dr. Ayman Saad and colleagues from the Blood and Marrow Transplantation and Cell Therapy Program in Birmingham, Alabama, write in an editorial accompanying the study.

"Many questions and issues need to be resolved before leukocyte telomere length can be used as one of the factors to determine the best available donor," they add. "Nevertheless, the report by Gadalla et al opens up a new area of scientific investigation. Further studies are warranted to define and optimize the potential role of leukocyte telomere length in selecting donors and improving outcomes for patients with severe aplastic anemia who receive HSCT."

This research was supported by the National Cancer Institute, the Nation Heart, Lung, and Blood Institute, the National Institute of Allergy and Infectious Diseases, Health Resources, Services Administration, and the Office of Naval Research. The authors report no disclosures.

信源地址:http://www.medscape.com/viewarticle/839709

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发表于 2015-2-27 16:09:53 | 显示全部楼层
这篇我领了~~

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发表于 2015-2-28 13:15:19 | 显示全部楼层
较长的供体染色体端粒可以提高器官移植的生存率

最新研究结果表明较长的供体白细胞端粒对接受造血细胞移植的再生障碍性贫血患者可能意味着更长的生存率。

端粒是保护染色体末端的非编码重复DNA序列。来自马里兰州罗克维尔的国家癌症研究所的Shahinaz Gadalla博士及其同事于2月10号在JAMA杂志上在线发表了一篇研究报告,报告中指出端粒的长度会随着细胞分裂而变短。

研究人员指出:当再生障碍性贫血患者接受造血细胞移植时,为了实现成功植入,移植供体细胞必须复制并且迅速扩增,有研究已经表明在移植后供体的端粒细胞会加速变短。

为了探索在造血细胞移植前受体和供体的相对白细胞端粒长度是否和移植结果相关,在84个不同医学中心,研究者观测了330个接受来自不相关受体的造血细胞移植的患者,并且使用了国际血液和骨髓移植研究中心的数据。患者在1989年到2007年之间接受治疗并随访到2013年3月。

供体和受体的端粒长度按照长(第三组,n=113)或者短(第一组和第二组,n=217)区分。

相对于接受受体较长端粒的患者五年生存率为56%,接受受体短端粒的病人五年生存率为40%, (p=.009)。同时两组病人一年生存率分别为60%和50%,三年生存率分别为58%和44%。

当研究者们调节了供体的年龄和另外几种因子,两组病人的关系还是具有显著差异性的,危险比为0.61。
当研究者基于严重再生障碍性贫血亚型,受体年龄,人白细胞抗原比配,移植年限以及预处理进行结果分析时所得到的结果是相似的。

然而,研究者们发现供体的端粒长度和嗜中性粒细胞植入后28天或者100天或者1年时移植物抗宿主反应之间是没有关联的。受体者在移植进行之前的白细胞端粒长度同移植后的生存率也是没有相关性的。

Gadalla 博士通过电子邮件告诉路透社健康新闻:“我们的研究表明,对于接受造血细胞移植的严重的再生障碍性贫血患者来说, 较长的端粒长度是和较长的生存率相关的”。这项研究第一次表明供体的端粒长度在造血细胞移植的进展中发挥着作用。在由观测转向临床应用之前需要收集大量的病例进行一项重复研究。

她补充道:“在目前的阶段,建议增加端粒长度的测量作为受体选择的标准之一还为时尚早。我们仍旧还有许多工作需要进行包括但是不局限于确定测量供体端粒长度的最佳方法以及确定哪些病人可以从具有较长端粒的受体那里获得最优的治疗效果。”

来自位于亚拉巴马伯明翰的血液与骨髓移植细胞治疗项目的Ayman Saad博士及其同事在该项研究所附的评论中写到假定生存率和移植状态不相关的话,拥有较长端粒长度的受体较高生存率背后的具体机制目前还不明了。

“白细胞端粒的长度作为一个确定最优供体的指标之前仍有许多问题有待解决。”他们补充道。“然而Gadalla等的报道开辟了科学研究的新领域。更深入的研究有待去定义和优化白细胞端粒长度在悬着供体以及提升接受造血细胞移植的严重再生障碍性贫血患者的治疗效果的潜在作用。”
这项研究由国家癌症研究所,国家心,肺,血液研究所,国家过敏和传染病研究所,卫生资源服务管理处以及海军研究办公室支持。作者报告未披露。


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 楼主| 发表于 2015-3-3 09:11:49 | 显示全部楼层
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