Kröger N
Department for Stem Cell Transplantation, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
Leukemia. 2007 Sep;21(9):1851-8. doi: 10.1038/sj.leu.2404775. Epub 2007 Jun 14.
Allogeneic stem cell transplantation in multiple myeloma after standard myeloablative conditioning induces a high rate of complete remissions, but long-term freedom from disease is achieved in 30-40% of the cases only. The therapeutic effect of allogeneic stem cell transplantation is due to cytotoxicity of high-dose chemotherapy and immune-mediated graft-versus-myeloma effect by donor T cells. Retrospective studies clearly suggest that both (a) reducing the intensity of high-dose chemotherapy by using reduced-intensity or non-myeloablative conditioning regimen or (b) reducing the immunotherapy of donor T cells by using T-cell depletion result in lower treatment-related morbidity and mortality, but also in higher rate of relapse. Therefore, this review will focus on potential strategies of how treatment-related morbidity and mortality might be kept low without an increased risk of relapse and how remission status after transplantation can be enhanced by using the newly established donor immunosystems after allografting as a platform for post-transplant treatment strategies with new drugs (thalidomide, lenalidomide, bortezomib) or immunotherapy (donor lymphocyte infusion, vaccination, tumor-specific T cells) in order to achieve remission on a molecular level, which seems to be a 'conditio sine qua non' to cure myeloma patients.
在标准清髓性预处理后进行异基因干细胞移植治疗多发性骨髓瘤，可诱导较高的完全缓解率，但只有30%-40%的患者能实现长期无病生存。异基因干细胞移植的治疗效果归因于大剂量化疗的细胞毒性作用以及供体T细胞介导的免疫性移植物抗骨髓瘤效应。回顾性研究清楚地表明，（a）采用减低强度或非清髓性预处理方案降低大剂量化疗的强度，或（b）采用T细胞去除法降低供体T细胞的免疫治疗强度，均会导致较低的治疗相关发病率和死亡率，但也会导致较高的复发率。因此，本综述将聚焦于如何在不增加复发风险的情况下降低治疗相关发病率和死亡率的潜在策略，以及如何通过将移植后新建立的供体免疫系统作为使用新药（沙利度胺、来那度胺、硼替佐米）或免疫治疗（供体淋巴细胞输注、疫苗接种、肿瘤特异性T细胞）进行移植后治疗策略的平台，以在分子水平上实现缓解，从而提高移植后的缓解状态，这似乎是治愈骨髓瘤患者的“必要条件”。
