Bensinger William I
Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Clin Adv Hematol Oncol. 2004 Jan;2(1):46-52.
Multiple myeloma is often successfully controlled with conventional chemotherapy, but complete remissions are uncommon and cure is rare. High-dose therapy followed by autologous or allogeneic stem cells, employed for the treatment of multiple myeloma in the past 20 years, is promising as a means to increase remission rates and improve survival. Autologous transplants have not always demonstrated survival benefits in randomized studies because most of the patients transplanted relapse, while patients given conventional therapy can receive salvage transplants when they relapse. Efforts to improve the results of autologous transplant include targeted radiation, cytoprotective agents, tandem transplants, or post-transplant immunotherapy. Only allogeneic hematopoietic stem cell transplantation is potentially curative, due to a graft-versus-myeloma effect. While patients who receive either allogeneic or autologous stem cell transplants for multiple myeloma have similar 3-5 year survival, only allograft recipients appear to enjoy long-term disease-free survival. High transplant-related mortality associated with allogeneic stem cell transplantation is currently the major limitation to wider use of this potentially curative modality. Strategies designed to improve the therapeutic index of allografts include the use of nonablative conditioning regimens, peripheral blood cells rather than bone marrow, graft engineering, and targeted conditioning therapies such as bone-seeking radioisotopes.
多发性骨髓瘤通常可通过传统化疗得到有效控制,但完全缓解并不常见,治愈更是罕见。在过去20年中,用于治疗多发性骨髓瘤的大剂量疗法继以自体或异基因干细胞移植,有望提高缓解率并改善生存率。自体移植在随机研究中并非总能显示出生存获益,因为大多数接受移植的患者会复发,而接受传统治疗的患者复发时可接受挽救性移植。改善自体移植效果的努力包括靶向放疗、细胞保护剂、串联移植或移植后免疫疗法。由于移植物抗骨髓瘤效应,只有异基因造血干细胞移植具有潜在治愈性。虽然接受自体或异基因干细胞移植治疗多发性骨髓瘤的患者3至5年生存率相似,但只有接受同种异体移植的患者似乎能实现长期无病生存。与异基因干细胞移植相关的高移植相关死亡率是目前限制这种潜在治愈性治疗方法更广泛应用的主要因素。旨在提高同种异体移植治疗指数的策略包括使用非清髓性预处理方案、外周血细胞而非骨髓、移植物工程以及靶向预处理疗法,如亲骨性放射性同位素。