Pandit Sandeep, Vesole David H
Department of Medicine, Medical College of Wisconsin, Milwaukee 53226, USA.
Oncology (Williston Park). 2002 Sep;16(9):1268-74; discussion 1274-6.
An estimated 14,600 new cases of multiple myeloma will be diagnosed in the United States in 2002. Multiple myeloma remains an incurable disease despite significant improvements in complete response rates and overall survival through the use of autologous stem cell transplantation. Allogeneic transplantation offers the advantage of a tumor-free graft and a graft-vs-myeloma effect but has been associated with a high mortality rate from transplant-related complications-primarily graft-vs-host disease (GVHD). As immunotherapy for patients with relapsed myeloma, donor lymphocyte infusion has resulted in response rates of over 50%, but many of these responses are not durable. In addition, donor lymphocyte infusion is associated with a significant risk of moderate-to-severe GVHD. In an attempt to decrease the high transplant-related mortality of conventional allogeneic transplants and to employ the proven efficacy of immunoreactive donor T lymphocytes, the use of nonmyeloablative transplants or "mini-transplants" is increasing. This approach has succeeded in significantly reducing transplant-related mortality but still may not be sufficient in producing long-term remissions or cures in myeloma patients. A combination of an autologous transplant (to achieve maximal cytoreduction) and a mini-transplant with donor lymphocyte infusion (for the immunoablative effect of alloreactive T lymphocytes) followed by maintenance therapy (thalidomide [Thalomid], steroids, cytokines, vaccines) for long-term immunomodulation is being investigated as a potential cure for this challenging disease.
2002年,美国预计有14,600例新的多发性骨髓瘤病例被诊断出来。尽管通过自体干细胞移植,完全缓解率和总生存率有了显著提高,但多发性骨髓瘤仍然是一种无法治愈的疾病。异基因移植具有提供无肿瘤移植物和移植物抗骨髓瘤效应的优势,但与移植相关并发症(主要是移植物抗宿主病,GVHD)导致的高死亡率相关。作为复发骨髓瘤患者的免疫疗法,供体淋巴细胞输注已使缓解率超过50%,但其中许多缓解并不持久。此外,供体淋巴细胞输注与中重度GVHD的显著风险相关。为了降低传统异基因移植的高移植相关死亡率,并利用免疫活性供体T淋巴细胞已证实的疗效,非清髓性移植或“微型移植”的使用正在增加。这种方法已成功显著降低了移植相关死亡率,但在骨髓瘤患者中产生长期缓解或治愈可能仍不足够。一种自体移植(以实现最大程度的细胞减少)与微型移植及供体淋巴细胞输注(用于同种异体反应性T淋巴细胞的免疫清除效应)相结合,随后进行维持治疗(沙利度胺[反应停]、类固醇、细胞因子、疫苗)以进行长期免疫调节的联合治疗正在作为这种具有挑战性疾病的潜在治愈方法进行研究。