High-dose therapy and autologous peripheral blood stem cell transplantation in multiple myeloma: Up-front or rescue treatment? Results of a multicenter sequential randomized clinical trial
High-dose therapy and autologous peripheral blood stem cell transplantation in multiple myeloma: Up-front or rescue treatment? Results of a multicenter sequential randomized clinical trial
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DOI：
10.1182/blood.v92.9.3131.421k30_3131_3136
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发表时间：
1998-11-01
期刊：
影响因子：
20.3
通讯作者：
Brouet, JC
中科院分区：
文献类型：
--
作者：
Fermand, JP;Ravaud, P;Brouet, JC
迄今为止的结果表明，自体干细胞支持的高剂量治疗（HDT）可改善症状性多发性骨髓瘤（MM）患者的生存率。我们进行了一项多中心、序贯、随机试验，旨在评估HDT和自体移植的最佳时机。在202例年龄在56岁以下的患者中，185例被随机分配接受HDT和外周血干细胞（PBSC）自体移植（早期HDT组，n = 91）或常规剂量化疗（CCT）方案（晚期HDT组，n = 94）。晚期HDT组在CCT原发耐药或缓解者复发时行HDT和移植作为补救治疗。在随机分组前、化疗动员后采集外周血干细胞，在两组中，HDT之前用长春新碱、多柔比星和甲基强的松龙进行3或4次治疗。采用序贯设计，在意向治疗基础上分析数据。在中位随访58个月内，早期HDT组的估计中位总生存期（OS）为64.6个月，速率组为64个月。生存曲线没有差异（P = 0.92，对数秩检验）。早期HDT组的中位无事件生存期（EFS）为39个月，而晚期HDT组从随机化到CCT失败的中位时间为13个月。两组中无症状、治疗和治疗毒性的平均时间（TWISTT）分别为27.8个月（95%置信区间[Cl];范围，23.8 - 31.8）和22.3个月（范围，16.0 - 28.6）。HDT联合PBSC移植在年轻症状性MM患者中获得的中位OS超过5年，无论是早期作为一线治疗还是晚期作为补救治疗。早期HDT可能是首选的，因为它与较短的化疗时间有关。(C)1998年，美国血液学会。
Results to date indicate that high-dose therapy (HDT) with autologous stem cell support improves survival of patients with symptomatic multiple myeloma (MM). We performed a multicenter, sequential, randomized trial designed to assess the optimal timing of HDT and autotransplantation. Among 202 enrolled patients who were up to 56 years old, 185 were randomly assigned to receive HDT and peripheral blood stem cell (PBSC) autotransplantation (early HDT group, n = 91) or a conventional-dose chemotherapy (CCT) regimen (late HDT group, n = 94). In the late HDT group, HDT and transplantation were performed as rescue treament, in case of primary resistance to CCT or at relapse in responders. PBSC were collected before randomization, after mobilization by chemotherapy, and, in the two groups, HDT was preceded by three or four treatments with vincristine, doxorubicin, and methylprednisolone. Data were analyzed on an intent-to-treat basis using a sequential design. Within a median follow-up of 58 months, estimated median overall survival (OS) was 64.6 months in the early HDT group and 64 months in the rate group. Survival curves were not different (P = .92, log-rank test). Median event-free survival (EFS) was 39 months in the early HDT group whereas median time between randomization and CCT failure was 13 months in the late group. Average time without symptoms, treatment, and treatment toxicity (TWISTT) were 27.8 months (95% confidence interval [Cl]; range, 23.8 to 31.8) and 22.3 months (range, 16.0 to 28.6) in the two groups, respectively. HDT with PBSC transplantation obtained a median OS exceeding 5 years in young patients with symptomatic MM, whether performed early, as first-line therapy, or late, as rescue treatment. Early HDT may be preferred because it is associated with a shorter period of chemotherapy. (C) 1998 by The American Society of Hematology.