大剂量美法仑与环磷酰胺、依托泊苷联合白消安预处理方案在多发性骨髓瘤自体造血干细胞移植中的比较

High dose melphalan(HDM)is superior to cyclophosphamide plus etoposide and busulfan(CVB)as the conditioning regimen in autologous stem cell transplantation for multiple myeloma

目的 比较大剂量美法仑(HDM)和环磷酰胺、依托泊苷联合白消安(CVB)预处理方案应用于新诊断多发性骨髓瘤(NDMM)患者自体造血干细胞移植(ASCT)的安全性、近期及远期疗效.方法 回顾性分析2011年1月至2017年8月期间接受PAD(硼替佐米+脂质体阿霉素+地塞米松)方案诱导治疗序贯ASCT的NDMM患者共123例,按接受预处理方案分为CVB组(82例)和HDM组(41例).结果 ①非血液学不良反应方面两者无显著区别.②CVB组中性粒细胞植入和血小板植入较HDM组快,中性粒细胞植入时间为第10(9~35)天对第11(9~12)天(z=-3.433,P=0.001);血小板植入时间为11(7~55)d对HDM组13(10~35)d(z=-3.506,P<0.001);但CVB组也更早进入粒细胞缺乏(粒缺)及显著血小板减少,最终粒缺及显著血小板减少持续时间两组间尚未显示出差别;但CVB组的发热持续时间以及相应抗生素使用时间显著延长.③CVB组经过移植后获得传统疗效进步的患者比例显著低于HDM组(9/46对14/28,P=0.021);而且移植后3个月CVB组的微小残留病(MRD)阴性率有低于HDM组的趋势(31.7%对48.8%,P=0.065).④无论单因素还是多因素分析均显示两种预处理方案并不影响接受PAD诱导序贯ASCT及维持治疗的NDMM患者的至进展时间(TTP)(P=0.619)及总生存(OS)时间(P=0.295).结论 HDM预处理方案血液学不良反应、减低MM肿瘤负荷以及使用方便性方面较CVB方案具有优势,但采用两种预处理方案的ASCT治疗MM的TTP和OS未见明显差异.

Objective To compare the efficacy,response and survival between high-dose melphalan(HDM)and cyclophosphamide+etoposide+busulfan(CVB)as the conditioning regimen in autologous stem cell transplantation(ASCT)for newly diagnosed multiple myeloma(NDMM).Methods Retrospectively enrolled 123 consecutive NDMM patients who had received PAD induction with subsequent ASCT from Jan 2011 to Aug 2017.The CVB group and HDM group had 82 and 41 patients respectively.Results①No differences existed between these 2 groups in non-hematological side effects.②Patients of CVB group had faster neutrophil and platelet engraftment time,with the median neutrophil engraftment time of 10(9-35)day vs 11(9-12)day for patients of HDM group(z=-3.433,P=0.001),and with median platelet engraftment time of 11(7-55)day vs 13(10-35)day for patients of HDM group(z=-3.506,P<0.001).CVB group entered neutropenia and severe thrombocytopenia more earlier than the HDM group,resulting similar neutropenia duration and severe thrombocytopenia duration between the CVB group and HDM group.However,patients of CVB group had significantly longer fever persistent time and antibiotic administration time.③The response rate was significantly lower in patients of CVB group vs.patients of HDM group(9/46 vs 14/28,P=0.021).Further,the minimal residual disease(MRD)negative rate at 3rd month post-transplantation seemed to be lower in CVB group than that in HDM group(31.7%vs 48.8%,P=0.065).④Both the univariate and multivariate analysis showed that HDM and CVB groups had similar duration to progression(TTP)(P=0.619)and overall survival(OS)(P=0.295).Conclusion HDM conditioning regimen is superior to CVB regimen in hematological side effects,tumor burden reduction and administration convenience.However,these two regimen had similar TTP and OS in MM patients receiving ASCT.