Lokhorst H M, Sonneveld P, Cornelissen J J, Joosten P, van Marwijk Kooy M, Meinema J, Nieuwenhuis H K, van Oers M H, Richel D J, Segeren C N, Veth G, Verdonck L F, Wijermans P W
Department of Hematology, University Hospital Utrecht, The Netherlands.
Bone Marrow Transplant. 1999 Feb;23(4):317-22. doi: 10.1038/sj.bmt.1701574.
We performed a phase II study to test the efficacy and feasibility of induction therapy with vincristine, adriamycin and dexamethasone (VAD) and intermediate-dose melphalan, 70 mg/m2 (IDM), to autologous or allogeneic stem cell transplantation in newly diagnosed multiple myeloma (MM). A total of 77 patients received two cycles of VAD (n = 62) and/or two cycles of i.v. IDM 70 mg/m2 (n = 15) combined with G-CSF. PBSC were harvested after the first IDM, successfully in 87% of patients. Patients with a response to induction received myeloablative therapy with PBSCT (n = 50) followed by IFN maintenance or allo-BMT (n = 11). Seventy-two per cent of patients achieved a response after VAD which increased to 85% after IDM. Of patients who received PBSCT and allo-BMT, 24% and 45% achieved CR, respectively. Toxicity of induction consisted mainly of bone marrow suppression after IDM (median 8 days) with prolonged aplasia in 11% of patients after the second IDM. Only six infections WHO grade 3 occurred during induction. Treatment-related mortality of PBSCT and allo-BMT was 6% and 18%, respectively. Median time of follow-up is 44 months, and 50% of patients after PBSCT and 60% of patients after allo-BMT are still in remission. Survival rates of all patients were 82%, 75% and 63%, and for transplanted patients 86%, 79% and 68% after 12, 24 and 36 months. Well known prognostic factors, including alpha-IFN maintenance after PBSCT, were not significant for response or survival although patients in CR after allo-BMT had a strong tendency for better outcome. VAD/IDM is an effective and safe induction therapy for autologous and allogeneic stem cell transplantation. Based on these observations a phase III trial was started in October 1995 comparing IFN maintenance with PBSCT and allo-BMT after response to induction with VAD and IDM.
我们开展了一项II期研究，以测试长春新碱、阿霉素和地塞米松（VAD）诱导疗法及70mg/m²中剂量美法仑（IDM）对新诊断的多发性骨髓瘤（MM）进行自体或异基因干细胞移植的疗效和可行性。共有77例患者接受了两个周期的VAD（n = 62）和/或两个周期的静脉注射70mg/m² IDM（n = 15）并联合使用粒细胞集落刺激因子（G-CSF）。首次IDM后采集外周血干细胞（PBSC），87%的患者采集成功。诱导治疗有反应的患者接受含PBSCT的清髓性治疗（n = 50），随后进行干扰素维持治疗或异基因骨髓移植（allo-BMT，n = 11）。72%的患者VAD治疗后有反应，IDM治疗后这一比例增至85%。接受PBSCT和allo-BMT的患者中，分别有24%和45%达到完全缓解（CR）。诱导治疗的毒性主要为IDM后的骨髓抑制（中位时间8天），第二次IDM后11%的患者出现长期再生障碍。诱导治疗期间仅发生6例WHO 3级感染。PBSCT和allo-BMT的治疗相关死亡率分别为6%和18%。中位随访时间为44个月，PBSCT后50%的患者和allo-BMT后60%的患者仍处于缓解状态。所有患者12、24和36个月后的生存率分别为82%、75%和63%；移植患者的生存率分别为86%、79%和68%。包括PBSCT后α干扰素维持治疗在内的已知预后因素对反应或生存均无显著影响，尽管allo-BMT后达到CR的患者有预后更好的强烈趋势。VAD/IDM是自体和异基因干细胞移植的一种有效且安全的诱导疗法。基于这些观察结果，1995年10月启动了一项III期试验，比较VAD和IDM诱导治疗有反应后，干扰素维持治疗与PBSCT及allo-BMT的疗效。
