Maloney David G, Sandmaier Brenda M, Mackinnon Stephen, Shizuru Judith A
Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA.
Hematology Am Soc Hematol Educ Program. 2002:392-421. doi: 10.1182/asheducation-2002.1.392.
The concept of utilizing enhanced immunosuppression rather than myeloablative cytotoxic conditioning has allowed the engraftment of allogeneic stem cells from related and unrelated donors with lower early transplant-related mortality (TRM) and morbidity. This approach shifts tumor eradication to the graft-vs-host immune response directed against minor histocompatibility antigens expressed on tumor cells. This is not without risk, as the long-term effects of graft-versus-host disease (GVHD), it's treatment, or resulting complications and immunodeficiency may be life threatening. However, this approach does allow the application of a potentially curative procedure to elderly or medically infirm patients who would not tolerate high-dose conditioning regimens. Section I, by Dr. Sandmaier, describes the current use of nonmyeloablative regimens and matched related or unrelated donors for the treatment of patients with CLL, CML, acute leukemia, MDS, lymphoma, and myeloma. In Section II, Dr. Maloney discusses the use of cytoreductive autologous followed by planned non-myeloablative allografts as treatment for patients with myeloma or NHL. This tandem transplant approach has a lower TRM than conventional high dose allografting. The nonmyeloablative allograft may allow the graft-versus-tumor (GVT) immune response to eradicate the minimal residual disease that causes nearly all patients with low-grade NHL or myeloma to relapse following autologous transplantation. In Section III, Dr. Mackinnon discusses the risks and benefits of T cell depletion strategies to prevent acute GVHD, while retaining GVT activity by planned donor lymphocyte infusions. Finally, in Section IV, Dr. Shizuru discusses the relationship between GVHD and GVT activity. Future studies, employing a greater understanding of these issues and the separation of GVHD from GVT activity by immunization or T cell cloning, may allow nonmyeloablative allogeneic transplantation to be safer and more effective.
利用强化免疫抑制而非清髓性细胞毒性预处理的概念，已使得来自相关和无关供者的异基因干细胞得以植入，且早期移植相关死亡率（TRM）和发病率较低。这种方法将肿瘤根除转移至针对肿瘤细胞上表达的次要组织相容性抗原的移植物抗宿主免疫反应。这并非没有风险，因为移植物抗宿主病（GVHD）及其治疗、或由此产生的并发症和免疫缺陷的长期影响可能危及生命。然而，这种方法确实允许将一种潜在的治愈性程序应用于无法耐受高剂量预处理方案的老年或身体虚弱的患者。第一节由桑德迈尔博士撰写，描述了非清髓性方案以及匹配的相关或无关供者目前在治疗慢性淋巴细胞白血病（CLL）、慢性粒细胞白血病（CML）、急性白血病、骨髓增生异常综合征（MDS）、淋巴瘤和骨髓瘤患者中的应用。在第二节中，马洛尼博士讨论了采用细胞减灭性自体移植随后进行计划性非清髓性同种异体移植作为骨髓瘤或非霍奇金淋巴瘤（NHL）患者的治疗方法。这种串联移植方法的TRM低于传统的高剂量同种异体移植。非清髓性同种异体移植可能使移植物抗肿瘤（GVT）免疫反应根除导致几乎所有低度NHL或骨髓瘤患者自体移植后复发的微小残留病。在第三节中，麦金农博士讨论了预防急性GVHD的T细胞去除策略的风险和益处，同时通过计划性供者淋巴细胞输注保留GVT活性。最后，在第四节中，志津留博士讨论了GVHD与GVT活性之间的关系。未来的研究，通过对这些问题有更深入的了解，并通过免疫或T细胞克隆将GVHD与GVT活性分开，可能会使非清髓性异基因移植更安全、更有效。
