Wada M, Mizoguchi H
Dept. of Hematology, Tokyo Women's Medical College, Japan.
Gan To Kagaku Ryoho. 1997 Jul;24(9):1079-88.
Melphalan and prednisolone (MP) have been the standard therapy for multiple myeloma for more than 25 years. Although they produce an objective response in 50-60% of patients, complete remission (CR) is rare and the median survival period is generally 24 to 30 months. Many combination chemotherapeutic agents have been used and resulted in approximately 70% objective response, but the median duration of survival has not significantly been improved. VAD regimen is effective for many patients with myeloma resistant to MP therapy. Furthermore, VAD-cyclosporin combination induces responses in approximately 40% of patients with VAD-resistant myeloma, with increased expression of the multi-drug resistant gene (MDR). Intravenous administration of high dose-melphalan also produces responses in approximately 30% of patients with myeloma resistant to VAD. Interferon-alpha therapy with an alkylating agent-glucocorticoid regimen, shows a higher response rate but similar survival time, compared with those obtained with the MP therapy alone. High-dose therapy with transplantation is promising. High-dose therapy combined with autologous bone marrow transplantation improves the response rate, event-free survival (EFS), and overall survival (OS) in patients with myeloma, demonstrated in the prospective, randomized trial by Attal et al. Total therapy by Barlogie et al. consisted of non-cross-resistant induction regimens, followed by a double autotransplantation (AT) procedure. Compared with the outcome of patients receiving standard therapy, dose intensification with double AT produces not only higher CR rates but also significantly extends EFS and OS in previously untreated patients with myeloma. The reduced mortality rate associated with transplantation, and development of new chemotherapeutic agents will lead to future improvements of the therapy for multiple myeloma.
美法仑和泼尼松（MP）作为多发性骨髓瘤的标准疗法已超过25年。尽管它们能使50%至60%的患者产生客观反应，但完全缓解（CR）很少见，中位生存期一般为24至30个月。许多联合化疗药物已被使用，客观反应率约为70%，但中位生存期并未得到显著改善。VAD方案对许多对MP疗法耐药的骨髓瘤患者有效。此外，VAD与环孢素联合使用能使约40%对VAD耐药的骨髓瘤患者产生反应，同时多药耐药基因（MDR）表达增加。静脉注射高剂量美法仑也能使约30%对VAD耐药的骨髓瘤患者产生反应。与单独使用MP疗法相比，α干扰素联合烷化剂-糖皮质激素方案治疗显示出更高的反应率，但生存期相似。高剂量移植治疗很有前景。Attal等人进行的前瞻性随机试验表明，高剂量治疗联合自体骨髓移植可提高骨髓瘤患者的反应率、无事件生存期（EFS）和总生存期（OS）。Barlogie等人的全程治疗包括非交叉耐药诱导方案，随后进行两次自体移植（AT）。与接受标准治疗的患者结果相比，两次AT强化剂量不仅能提高CR率，还能显著延长既往未治疗的骨髓瘤患者的EFS和OS。与移植相关的死亡率降低以及新化疗药物的研发将引领未来多发性骨髓瘤治疗的改善。
