Schwinghammer T L, Bloom E J
Department of Pharmacy and Therapeutics, School of Pharmacy, University of Pittsburgh, PA 15261.
Clin Pharm. 1993 Oct;12(10):736-61.
The immunology, pathophysiology, incidence, clinical manifestations, grading, and prevention of acute graft-versus-host disease (GVHD) are reviewed. GVHD occurs after allogeneic marrow transplantation when immunologically competent T lymphocytes in the donor marrow identify the host's antigens as foreign and attempt to reject host tissues. Acute GVHD occurs within three months after marrow transplantation and may affect the skin, gastrointestinal tract, liver, and immune system. Even with prophylactic immunosuppression, acute GVHD occurs in 20% to 80% of patients. Moderate to severe GVHD (grades II-IV) is a major cause of morbidity and mortality after allogeneic bone marrow transplantation. Conventional GVHD prophylaxis consists of immunosuppressives such as corticosteroids, methotrexate, and cyclosporine. Methotrexate and cyclosporine are equally effective in preventing GVHD. A combination of both drugs is better than either drug alone and results in an improved survival rate. The addition of corticosteroids to methotrexate, cyclosporine, or antithymocyte globulin is also more effective than single-drug therapy. Serial administration of intravenous immune globulin may contribute additional protection against acute GVHD. There is conflicting evidence concerning the prophylactic efficacy of pentoxifylline. Elimination of T lymphocytes from the donor marrow before transplantation has been associated with less GVHD but a higher incidence of graft failure. Total elimination of GVHD in patients with leukemia may cause loss of a graft-versus-leukemia effect, resulting in increased relapse rates and decreased long-term survival. Promising experimental prophylactic agents include thalidomide, zolimomab aritox, tacrolimus, antibodies to cytokines involved in the pathogenesis of GVHD, and monoclonal antibodies against cytokine receptors on T lymphocytes. Current research efforts are also directed toward eliminating GVHD without compromising the graft-versus-leukemia effect.
本文综述了急性移植物抗宿主病（GVHD）的免疫学、病理生理学、发病率、临床表现、分级及预防。GVHD发生于异基因骨髓移植后，供体骨髓中的免疫活性T淋巴细胞将宿主抗原识别为外来抗原并试图排斥宿主组织。急性GVHD发生在骨髓移植后的三个月内，可累及皮肤、胃肠道、肝脏和免疫系统。即使采用预防性免疫抑制，仍有20%至80%的患者会发生急性GVHD。中重度GVHD（II-IV级）是异基因骨髓移植后发病和死亡的主要原因。传统的GVHD预防措施包括使用皮质类固醇、甲氨蝶呤和环孢素等免疫抑制剂。甲氨蝶呤和环孢素在预防GVHD方面效果相当。两种药物联合使用比单独使用任何一种药物效果更好，可提高生存率。在甲氨蝶呤、环孢素或抗胸腺细胞球蛋白中添加皮质类固醇也比单一药物治疗更有效。静脉注射免疫球蛋白的连续给药可能有助于提供额外的保护以预防急性GVHD。关于己酮可可碱的预防效果存在相互矛盾的证据。移植前从供体骨髓中清除T淋巴细胞与较少的GVHD相关，但移植失败的发生率较高。白血病患者完全消除GVHD可能会导致移植物抗白血病效应丧失，从而导致复发率增加和长期生存率降低。有前景的实验性预防药物包括沙利度胺、佐利莫单抗阿立托克斯、他克莫司、针对GVHD发病机制中涉及的细胞因子的抗体以及针对T淋巴细胞上细胞因子受体的单克隆抗体。目前的研究工作也致力于在不损害移植物抗白血病效应的情况下消除GVHD。
