Majolino I, Vignetti M, Meloni G, Vegna M L, Scimè R, Tringali S, Amaddii G, Coser P, Tribalto M, Raimondi R, Bergonzi C, Sajeva M R, Sica S, Ferrando F, Messina G, Mandelli F
Divisione di Ematologia e Centro Trapianti di Midollo Osseo, Azienda Ospedaliera V.Cervello, Via Trabucco 180, 90146 Palermo, Italy.
Haematologica. 1999 Sep;84(9):844-52.
Autologous transplantation is a better treatment for multiple myeloma (MM) than chemotherapy, but uncertainty remains about patient selection, optimal timing of autograft, conditioning regimen, need for a second autograft, and role of maintenance. To provide partial answers to these questions we assessed the results of autologous transplantation in a large cohort of patients whose data were reported to the GITMO registry.
We retrospectively analyzed data from 290 patients with MM (M = 150; F = 140; median age 52 years, range 19-70; stage I = 34, stage II = 75, stage III = 167) reported to the GITMO. At the time of autograft, 20% were in CR, 66% in PR, while the remaining had non-responsive or progressive disease. Median time between diagnosis and transplant was 16 months (1-90). Seventy-two patients (26%) had been planned to receive a double autograft, but this was actually done in only 35 (12%). The conditioning was chemotherapy in 90%. Peripheral blood was the only source of stem cells in 94%, and purging was applied in 10% of cases. For statistical analysis of data, differences between patient subsets were analyzed using the chi-square test, while the Kaplan-Meier method was used to estimate event-free survival (EFS) and survival (OS) probabilities. The Cox model was used for multivariate analysis.
Following the autograft, 116 patients (40%) were in CR, 144 (50%) in PR, 24 (8%) did not respond or progressed and 6 (2%) died before response evaluation. Transplant-related mortality occurred in 3%. At a median follow-up of 23 months, 223 (77%) patients are alive, 71 (24%) of them in CR, and 67 (23%) patients have died at a median time of 20 months (0-70). OS and EFS at 6 years are 47% and 28%, respectively, but the EFS curve shows no plateau. In multivariate analysis, age, beta2-microglobulin level and status at transplant emerged as significant prognostic factors for both OS and EFS, while time from diagnosis to transplant showed borderline significance.
Based on the prognostic factors identified in multivariate analysis, we were able to assess the weight of a single prognostic factor or their combinations on transplant outcome. We also calculated the probability of OS and EFS by the number of factors at the time of autograft. Autologous transplantation is a safe and effective procedure, not only in sensitive patients, but also in resistant cases, provided they are <55 years of age and have low beta2-microglobulin. It should be applied early after the diagnosis of multiple myeloma, following the delivery of brief primary chemotherapy.
自体移植治疗多发性骨髓瘤(MM)优于化疗,但在患者选择、自体移植的最佳时机、预处理方案、是否需要二次自体移植以及维持治疗的作用等方面仍存在不确定性。为部分解答这些问题,我们评估了一大群向GITMO登记处报告数据的患者的自体移植结果。
我们回顾性分析了向GITMO报告的290例MM患者的数据(男性 = 150例;女性 = 140例;中位年龄52岁,范围19 - 70岁;Ⅰ期 = 34例,Ⅱ期 = 75例,Ⅲ期 = 167例)。自体移植时,20%处于完全缓解(CR),66%处于部分缓解(PR),其余患者病情无反应或进展。诊断与移植之间的中位时间为16个月(1 - 90个月)。72例患者(26%)计划接受两次自体移植,但实际上仅35例(12%)进行了两次移植。90%的预处理为化疗。94%的患者外周血是干细胞的唯一来源,10%的病例进行了净化处理。对于数据的统计分析,使用卡方检验分析患者亚组之间的差异,同时使用Kaplan - Meier方法估计无事件生存(EFS)和总生存(OS)概率。Cox模型用于多变量分析。
自体移植后,116例患者(40%)处于CR,144例(50%)处于PR,24例(8%)无反应或病情进展,6例(2%)在反应评估前死亡。移植相关死亡率为3%。中位随访23个月时,223例(77%)患者存活,其中71例(24%)处于CR,67例(23%)患者死亡,中位死亡时间为20个月(0 - 70个月)。6年时的OS和EFS分别为47%和28%,但EFS曲线未显示平台期。在多变量分析中,年龄、β2 - 微球蛋白水平和移植时的状态是OS和EFS的显著预后因素,而从诊断到移植的时间显示出临界显著性。
基于多变量分析中确定的预后因素,我们能够评估单个预后因素或其组合对移植结果的影响程度。我们还根据自体移植时的因素数量计算了OS和EFS的概率。自体移植是一种安全有效的治疗方法,不仅适用于敏感患者,对于耐药患者也是如此,前提是他们年龄<55岁且β2 - 微球蛋白水平较低。多发性骨髓瘤诊断后应在进行简短的初始化疗后尽早进行自体移植。