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体外光分离术联合喷司他丁预处理在犬造血细胞移植中的作用:对植入的影响。

Extracorporeal photopheresis in addition to pentostatin in conditioning for canine hematopoietic cell transplantation: role in engraftment.

机构信息

Clinical Research Division, Transplantation Biology Program, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA 98109-1024, USA.

出版信息

Bone Marrow Transplant. 2011 Oct;46(10):1382-8. doi: 10.1038/bmt.2010.301. Epub 2010 Dec 13.

Abstract

Extracorporeal photopheresis (ECP) and the purine analog pentostatin exert potent immunomodulatory effects, but have not been evaluated for their ability to enhance engraftment of hematopoietic stem cells. We evaluated, in a canine model of dog leukocyte antigen (DLA)-identical hematopoietic cell transplantation (HCT), whether ECP in combination with pentostatin could enhance engraftment using a nonmyeloablative regimen consisting of 100 cGy TBI and postgrafting immunosuppression with mycophenolate mofetil and CYA. We have shown previously that with 100 cGy TBI alone as conditioning, all of the six dogs rejected their grafts 2-12 weeks after HCT. With the addition of pentostatin to 100 cGy TBI, 6 of 10 dogs rejected their graft. We now tested the additional use of ECP alone (n=2) or ECP and 3-6 doses of pentostatin (n=7) before 100 cGy TBI and HCT. Eight out of nine dogs rejected their grafts within 6-11 weeks after HCT. Compared with data without ECP, we failed to demonstrate a positive impact of the use of either ECP or pentostatin for prevention of rejection.

摘要

体外光分离(ECP)和嘌呤类似物戊柔比星具有强大的免疫调节作用,但尚未评估它们增强造血干细胞植入的能力。我们在犬白细胞抗原(DLA)匹配的造血细胞移植(HCT)的犬模型中评估了 ECP 联合戊柔比星是否可以通过非清髓性方案增强植入,该方案由 100 cGy TBI 和移植后用吗替麦考酚酯和 CYA 进行免疫抑制。我们之前已经表明,在单独使用 100 cGy TBI 作为预处理的情况下,所有 6 只狗在 HCT 后 2-12 周内均排斥其移植物。在用戊柔比星加 100 cGy TBI 处理时,10 只狗中有 6 只排斥移植物。现在,我们在 100 cGy TBI 和 HCT 前单独使用 ECP(n=2)或 ECP 和 3-6 剂戊柔比星(n=7)进行了测试。HCT 后 6-11 周内,9 只狗中有 8 只排斥其移植物。与没有 ECP 的数据相比,我们未能证明使用 ECP 或戊柔比星预防排斥反应具有积极影响。

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