Vesole D H, Tricot G, Jagannath S, Desikan K R, Siegel D, Bracy D, Miller L, Cheson B, Crowley J, Barlogie B
Division of Hematology/Oncology, University of Arkansas for Medical Sciences, Little Rock, USA.
Blood. 1996 Aug 1;88(3):838-47.
Of 496 consecutive patients with multiple myeloma (MM) enrolled in clinical trials of tandem transplants with peripheral blood stem cells support, 470 (95%) completed the first autotransplant with melphalan 200 mg/m2 (MEL 200) and 363 (73%) completed the second transplant with either MEL 200 (40%), MEL 140 mg/m2 (MEL 140) with total-body irradiation (17%), or a combination of alkylating agents (16%), depending on the response status prior to the second transplant; 31 patients up to age 60 years received an allograft as the second transplant. The median interval from first to second transplant was 5 months. Treatment-related mortality during the first year after transplantation was 7%, and complete remission (CR) was obtained in 36%; the median durations of event-free survival (EFS) and overall survival (OS) after transplant were 26 and 41 months, respectively. Low beta 2-microglobulin ([B2M] < or = 2.5 mg/L) and C-reactive protein ([CRP] < or = 0.4 mg/dL) were the most significant standard parameters associated with both prolonged EFS and OS. Median OS exceeded 5.5 years in the one third of patients with both low B2M and CRP. When cytogenetics were included in the analysis, the presence of 11q abnormalities and/or complete or partial deletion of chromosome 13 ("unfavorable karyotype") became a dominant negative feature for both EFS and OS. In addition to these pretransplant parameters, attainment of CR and application of two transplants within 6 months both significantly extended EFS and OS. The group of patients (7%) with high B2M and CRP with either IgA isotype or unfavorable karyotype had the worst prognosis (EFS, < or = 10 months; median OS, < or = 12 months) and will require novel therapy. We conclude that tandem transplants are feasible in the majority of patients up to age 70 years, effecting CR in one third of all patients. Median OS was greater than 5.5 years, regardless of pretransplant features, if the first transplant was applied within 12 months of initial treatment and the second transplant no more than 6 months later.
在496例连续入组接受外周血干细胞支持的串联移植临床试验的多发性骨髓瘤（MM）患者中，470例（95%）完成了首次美法仑200mg/m²（MEL 200）自体移植，363例（73%）完成了第二次移植，第二次移植根据第二次移植前的缓解状态，分别采用MEL 200（40%）、140mg/m²美法仑（MEL 140）联合全身照射（17%）或烷化剂联合方案（16%）；31例60岁及以下患者接受了同种异体移植作为第二次移植。首次移植到第二次移植的中位间隔时间为5个月。移植后第一年的治疗相关死亡率为7%，36%的患者获得完全缓解（CR）；移植后无事件生存期（EFS）和总生存期（OS）的中位持续时间分别为26个月和41个月。低β2-微球蛋白（[B2M]≤2.5mg/L）和C反应蛋白（[CRP]≤0.4mg/dL）是与延长EFS和OS相关的最显著标准参数。在B2M和CRP均低的三分之一患者中，中位OS超过5.5年。当将细胞遗传学纳入分析时，11q异常和/或13号染色体完全或部分缺失（“不良核型”）的存在成为EFS和OS的主要负性特征。除了这些移植前参数外，达到CR以及在6个月内进行两次移植均显著延长了EFS和OS。B2M和CRP高且伴有IgA同种型或不良核型的患者组（7%）预后最差（EFS≤10个月；中位OS≤12个月），需要新的治疗方法。我们得出结论，串联移植在大多数70岁及以下患者中是可行的，在所有患者中有三分之一实现了CR。如果首次移植在初始治疗后12个月内进行，第二次移植不超过6个月后进行，无论移植前特征如何，中位OS均大于5.5年。
