Bethge W A, Kerbauy F R, Santos E B, Gooley T, Storb R, Sandmaier B M
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
1] Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA [2] Departments of Statistics, University of Washington, Seattle, WA, USA.
Bone Marrow Transplant. 2014 Sep;49(9):1198-204. doi: 10.1038/bmt.2014.137. Epub 2014 Jul 21.
Extracorporeal photopheresis (ECP) and the purine analog pentostatin exert potent immunomodulatory effects. We evaluated the use of these treatment modalities to prevent GVHD in a canine model of unrelated dog leukocyte Ag-mismatched hematopoietic cell transplantation, after conditioning with 920 cGy TBI. We have shown previously in this model that 36/40 dogs given MTX alone as postgrafting immunosuppression engrafted and that 25 of 40 dogs had severe GVHD and median survival of 21 days. In the current study, nine dogs received conditioning with 920 cGy TBI and postgrafting MTX either with ECP on days -2 to -1 alone (n=5) or ECP on days -6 and -5 combined with two doses of pentostatin (days -4 to -3) (n=4). Seven of nine dogs achieved engraftment. Six dogs developed severe acute GVHD (four in the group with ECP alone and two with pentostatin and ECP). We failed to demonstrate a positive impact of ECP and pentostatin for the prevention of GVHD compared with historical control dogs.
体外光化学疗法(ECP)和嘌呤类似物喷司他丁具有强大的免疫调节作用。我们评估了在经920 cGy全身照射预处理的非亲缘犬白细胞抗原不匹配造血细胞移植犬模型中,使用这些治疗方式预防移植物抗宿主病(GVHD)的效果。我们之前在此模型中已表明,40只犬中36只单独给予甲氨蝶呤(MTX)作为移植后免疫抑制得以植入,且40只犬中有25只发生严重GVHD,中位生存期为21天。在当前研究中,9只犬经920 cGy全身照射预处理并在移植后给予MTX,其中5只犬仅在第-2至-1天接受ECP,4只犬在第-6和-5天接受ECP并联合两剂喷司他丁(第-4至-3天)。9只犬中有7只实现植入。6只犬发生严重急性GVHD(单独接受ECP组中有4只,接受喷司他丁和ECP组中有2只)。与历史对照犬相比,我们未能证明ECP和喷司他丁对预防GVHD有积极影响。