Siegel D S, Desikan K R, Mehta J, Singhal S, Fassas A, Munshi N, Anaissie E, Naucke S, Ayers D, Spoon D, Vesole D, Tricot G, Barlogie B
Myeloma and Transplantation Research Center, University of Arkansas for Medical Sciences and Arkansas Cancer Research Center, Little Rock 72205, USA.
Blood. 1999 Jan 1;93(1):51-4.
Multiple myeloma (MM) typically afflicts elderly patients with a median age of 65 years. However, while recently shown to provide superior outcome to standard treatment, high-dose therapy (HDT) has usually been limited to patients up to 65 years. Among 550 patients with MM and a minimum follow-up of 18 months, 49 aged >/=65 years were identified (median age, 67; range, 65 to 76 years). Their outcome was compared with 49 younger pair mates (median, 52; range, 37 to 64 years) selected among the remaining 501 younger patients (<65 years) matched for five previously recognized critical prognostic factors (cytogenetics, beta2-microglobulin, C-reactive protein, albumin, creatinine). Nearly one half had been treated for more than 1 year with standard therapy and about one third had refractory MM. All patients received high-dose melphalan-based therapy; 76% of the younger and 65% of the older group completed a second transplant (P =.3). Sufficient peripheral blood stem cells to support two HDT cycles (CD34 > 5 x 10(6)/kg) were available in 83% of younger and 73% of older patients (P =.2). After HDT, hematopoietic recovery to critical levels of granulocytes (>500/microL) and of platelets (>50,000/microL) proceeded at comparable rates among younger and older subjects with both first and second HDT. The frequency of extramedullary toxicities was comparable. Treatment-related mortality with the first HDT cycle was 2% in younger and 8% among older subjects, whereas no mortality was encountered with the second transplant procedure. Comparing younger/older subjects, median durations of event-free and overall survival were 2.8/1.5 years (P =.2) and 4.8/3.3 years (P =.4). Multivariate analysis showed pretransplant cytogenetics and beta2-microglobulin levels as critical prognostic features for both event-free and overall survival, whereas age was insignificant for both endpoints (P =.2/.8). Thus, age is not a biologically adverse parameter for patients with MM receiving high-dose melphalan-based therapy with peripheral blood stem cell support and, hence, should not constitute an exclusion criterion for participation in what appears to be superior therapy for symptomatic MM.
多发性骨髓瘤(MM)通常困扰着中位年龄为65岁的老年患者。然而,虽然最近显示高剂量疗法(HDT)比标准治疗能带来更好的疗效,但通常仅限于65岁以下的患者。在550例MM患者中,至少随访18个月,确定了49例年龄≥65岁(中位年龄67岁;范围65至76岁)。将他们的疗效与从其余501例年龄较小的患者(<65岁)中挑选出的49例年龄较小的配对对象(中位年龄52岁;范围37至64岁)进行比较,这些配对对象在五个先前公认的关键预后因素(细胞遗传学、β2-微球蛋白、C反应蛋白、白蛋白、肌酐)方面相匹配。近一半患者接受标准治疗超过1年,约三分之一患者为难治性MM。所有患者均接受基于马法兰的高剂量疗法;年龄较小组76%和年龄较大组65%完成了第二次移植(P = 0.3)。83%的年龄较小患者和73%的年龄较大患者有足够的外周血干细胞支持两个HDT周期(CD34>5×10⁶/kg)(P = 0.2)。HDT后,年龄较小和年龄较大的患者在首次和第二次HDT时,粒细胞(>500/μL)和血小板(>50,000/μL)恢复到临界水平的造血恢复率相当。髓外毒性的发生率相当。首次HDT周期的治疗相关死亡率在年龄较小的患者中为2%,在年龄较大的患者中为8%,而第二次移植手术未出现死亡。比较年龄较小/较大的患者,无事件生存期和总生存期的中位持续时间分别为2.8/1.5年(P = 0.2)和4.8/3.3年(P = 0.4)。多因素分析显示,移植前细胞遗传学和β2-微球蛋白水平是无事件生存期和总生存期的关键预后特征,而年龄对两个终点均无显著影响(P = 0.2/0.8)。因此,对于接受基于马法兰的高剂量疗法并获得外周血干细胞支持的MM患者,年龄并非生物学上的不利参数,因此,不应构成参与似乎是有症状MM的更优疗法的排除标准。