Ho Vincent T, Cutler Corey
Department of Adult Oncology, Center for Hematologic Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, 44 Binney Street, D1B06, Boston, MA 02115, USA.
Best Pract Res Clin Haematol. 2008 Jun;21(2):223-37. doi: 10.1016/j.beha.2008.02.009.
Despite improvements in our understanding of transplant immunology and clinical and supportive care, acute graft-versus-host disease (GVHD) remains a clinical challenge and a major cause of morbidity and mortality for patients after allogeneic hematopoietic stem-cell transplantation. While systemic corticosteroid is standard primary therapy for acute GVHD, there is no established standard treatment in the steroid-refractory setting. New generations of monoclonal antibodies, biologics, and chemotherapeutics with immunomodulatory effects have been developed over the past decade, and are being tested as novel therapies in this disease. Many of these agents - including, among others, mycophenolate mofetil, anti-tumor necrosis factor-alpha antibodies, denileukin diftitox, and anti-interleukin-2Ralpha-chain antibodies - have demonstrated promising activity in steroid-refractory acute GVHD. Despite the high response rates, however, long-term survival remains poor due to a high incidence of infections. The key to improving acute GVHD outcomes may, in fact, rest upon successful initial therapy, and timely taper of corticosteroids to promote healthier immune reconstitution. Clinical trials combining these newer agents with systemic corticosteroids as initial treatment are under way, and will determine whether fortifying initial therapy will indeed reduce the development of steroid-refractory GVHD and improve long-term outcomes. In this article, we review current and novel agents available for acute GVHD, and discuss newer investigational approaches - such as phototherapy and cellular therapies - in the management of this common transplant complication.
尽管我们对移植免疫学以及临床和支持治疗的理解有所进步，但急性移植物抗宿主病（GVHD）仍然是一项临床挑战，并且是异基因造血干细胞移植术后患者发病和死亡的主要原因。虽然全身用皮质类固醇是急性GVHD的标准初始治疗方法，但在类固醇难治性情况下尚无既定的标准治疗方法。在过去十年中，已开发出新一代具有免疫调节作用的单克隆抗体、生物制剂和化学治疗药物，并正在作为该疾病的新型疗法进行测试。其中许多药物——包括霉酚酸酯、抗肿瘤坏死因子-α抗体、地尼白介素-毒素融合蛋白和抗白介素-2Rα链抗体等——已在类固醇难治性急性GVHD中显示出有前景的活性。然而，尽管缓解率很高，但由于感染发生率高，长期生存率仍然很低。事实上，改善急性GVHD预后的关键可能在于成功的初始治疗，以及及时逐渐减少皮质类固醇用量以促进更健康的免疫重建。将这些新型药物与全身用皮质类固醇联合作为初始治疗的临床试验正在进行中，这将确定加强初始治疗是否确实会减少类固醇难治性GVHD的发生并改善长期预后。在本文中，我们回顾了目前可用于急性GVHD的药物和新型药物，并讨论了在这种常见移植并发症管理中的新研究方法——如光疗和细胞疗法。
