Vesole D H, Barlogie B, Jagannath S, Cheson B, Tricot G, Alexanian R, Crowley J
Division of Hematology/Oncology, University of Arkansas for Medical Sciences, Little Rock 72205.
Blood. 1994 Aug 1;84(3):950-6.
One hundred and thirty-five patients with advanced and refractory myeloma received one of three high-dose therapy regimens: melphalan at doses of 90 to 100 mg/m2 (MEL 100; 47 patients) without autotransplant; total body irradiation (TBI; 850 cGy) with either melphalan 140 mg/m2 or thiotepa 750 mg/m2 and autologous bone marrow transplant (ABMT) (< or = 30% plasma cells; 21 patients); melphalan 200 mg/m2 (MEL 200) supported by both peripheral blood stem cells (PBSC) and ABMT plus GM-CSF intended as a double-transplant program (67 patients; 42 have completed and 3 are still awaiting a second autotransplant; 5 additional patients received an allograft for their second transplant). Mortality within 2 months of therapy was 20% to 25% with MEL 100 and TBI regimens, but less than 1% with MEL 200, mainly because severe neutropenia (< 500/microL) was shortened to less than 1 week due to infusion of PBSC and use of growth factor therapy. Low beta 2-microglobulin (beta 2M) levels < or = 2.5 mg/L and MEL 200 therapy were identified as the two most important independent favorable variables associated with prolonged event-free survival (EFS) and overall survival (OS). On the basis of these two parameters, three risk groups were defined: 29 good-risk patients with low beta 2M receiving MEL 200 had the best outcome, with median durations of EFS of 37 months and projected OS of > or = 43 months; 54 intermediate-risk patients displaying one of the two favorable parameters had EFS and OS durations of 16 and 36 months, respectively; and 52 poor-risk patients with high beta 2M not receiving MEL 200 had a dismal prognosis, with EFS of 3 months and OS of 5 months (all P < .0001). Further analysis that excluded treatment as a variable identified high beta 2M and resistant relapse as the two major adverse prognostic factors, one of which was present in 80% of the 135 patients. Among these 108 high-risk patients, prognosis was improved markedly with MEL 200 because of both better supportive care (PBSC and hematopoietic growth factors) and more intensive therapy using the double-transplant approach. This study supports the concept that safer and potentially more-effective therapies can be developed in the setting of advanced and resistant disease.
135例晚期难治性骨髓瘤患者接受了三种高剂量治疗方案中的一种：剂量为90至100mg/m²的美法仑（MEL 100；47例患者），不进行自体移植；全身照射（TBI；850cGy）联合140mg/m²美法仑或750mg/m²噻替派及自体骨髓移植（ABMT）（浆细胞≤30%；21例患者）；200mg/m²美法仑（MEL 200），以外周血干细胞（PBSC）和ABMT支持，并联合GM-CSF作为双移植方案（67例患者；42例已完成，3例仍在等待第二次自体移植；另有5例患者接受了同种异体移植作为第二次移植）。MEL 100和TBI方案治疗后2个月内的死亡率为20%至25%，而MEL 200方案则低于1%，主要是因为输注PBSC和使用生长因子治疗使严重中性粒细胞减少（<500/μL）缩短至不到1周。低β2-微球蛋白（β2M）水平≤2.5mg/L和美法仑200治疗被确定为与无事件生存期（EFS）延长和总生存期（OS）相关的两个最重要的独立有利变量。基于这两个参数，定义了三个风险组：29例低β2M且接受MEL 200治疗的低风险患者预后最佳，EFS中位数持续时间为37个月，预计OS≥43个月；54例显示两个有利参数之一的中风险患者，EFS和OS持续时间分别为16个月和36个月；52例高β2M且未接受MEL 200治疗的高风险患者预后不佳，EFS为3个月，OS为5个月（所有P<0.0001）。排除治疗作为变量的进一步分析确定高β2M和难治性复发为两个主要不良预后因素，135例患者中有80%存在其中之一。在这108例高风险患者中，由于更好的支持治疗（PBSC和造血生长因子）以及使用双移植方法进行更强化的治疗，MEL 200使预后显著改善。这项研究支持这样一种观念，即在晚期难治性疾病的背景下可以开发出更安全且可能更有效的治疗方法。
