Storb R, Weiden P L, Thomas E D
Postgrad Med J. 1976;52(5 Suppl):96-103.
Pre-sensitization was investigated in the dog marrow transplant model with donor and recipient mismatching at the canine major histocompatibility complex (MHC). Various prophylactic immunosuppressive regimes were used and it was concluded from these regimes that sensitization to histocompatibility antigens could be abrogated by a combination of procarbazine and antithymocyte serum (ATS) together, before total body irradiation. Subsequent work in humans showed that rejection of a bone marrow graft can be successfully treated by using the procarbazine-antithymocyte clobulin regime and a second transplant. Based upon animal studies, attempts were made to prevent graft-versus-host disease in humans by the use of methotrexate following grafting. Despite matching at the MHC and the use of methotrexate some recipients developed graft-versus-host disease with a fatal outcome. Further work using ATS in the immediate pre- and post-grafting period was inconclusive. Accordingly ATS was used in animals once graft-versus-host disease became manifest with drmatic improvement in clinical status. As a result it was decided to treat all patients who developed graft-versus-host disease with antithymocyte globulin (ATG). Under ATG therpy twelve out of nineteen patients showed complete resolution, and five showed improvement. Six patients became long term survivors. Of the remaining 13, 11 died on interstitial pneumonitis, and two of fungal and bacterial infections. ATG in estblished graft-versus-host disease appears capable of modigying an otherwise fatal disease in a therpeutically beneficial manner.
在犬类主要组织相容性复合体（MHC）供体和受体不匹配的犬类骨髓移植模型中研究了预致敏情况。使用了各种预防性免疫抑制方案，从这些方案得出的结论是，在全身照射前，丙卡巴肼和抗胸腺细胞血清（ATS）联合使用可消除对组织相容性抗原的致敏。随后在人类中的研究表明，使用丙卡巴肼 - 抗胸腺细胞球蛋白方案和第二次移植可以成功治疗骨髓移植排斥反应。基于动物研究，试图通过在移植后使用甲氨蝶呤来预防人类的移植物抗宿主病。尽管在MHC上匹配且使用了甲氨蝶呤，但一些接受者仍发生了移植物抗宿主病并导致致命后果。在移植前后立即使用ATS的进一步研究尚无定论。因此，在动物移植物抗宿主病明显出现且临床状况有显著改善时使用了ATS。结果决定用抗胸腺细胞球蛋白（ATG）治疗所有发生移植物抗宿主病的患者。在ATG治疗下，19名患者中有12名完全缓解，5名有所改善。6名患者成为长期存活者。其余13名患者中，11名死于间质性肺炎，2名死于真菌和细菌感染。已确诊的移植物抗宿主病使用ATG似乎能够以治疗有益的方式改变这种原本致命的疾病。
