Kim Jin Seok, Kim Kihyun, Cheong June-Won, Min Yoo Hong, Suh Cheolwon, Kim Hawk, Jo Deog Yeon, Ryoo Hun Mo, Yoon Sung Soo, Lee Jae Hoon
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
Biol Blood Marrow Transplant. 2009 Apr;15(4):463-70. doi: 10.1016/j.bbmt.2008.12.512.
Upfront high-dose myeloablative chemotherapy followed by a single autologous stem cell transplantation (ASCT) is the standard therapy for patients under the age of 65 years with newly diagnosed multiple myeloma (MM). Because disease status after induction chemotherapy is variable, we evaluated the prognostic effect of disease status before ASCT, especially in patients who were initially chemosensitive. We retrospectively analyzed the initially chemosensitive MM patients (> or = partial remission [PR]) enrolled in the Korean Multiple Myeloma Working Party Web-based registration system (www.myeloma.or.kr). Between November 1996 and January 2007, 197 MM patients (median age 53 years) were treated with induction chemotherapy followed by a single ASCT. All patients received peripheral blood stem cell (PBSC) support after conditioning with melphalan (Mel) alone. We considered those patients with no detectable M-protein regardless of the result of immunofixation to be in complete remission (CR) in this study. The median follow-up times were 29.2 months (range, 5.4 to 103.8 months) from the day of diagnosis and 22.4 months (range, 0.4 to 96.0 months) from the day of ASCT. Before ASCT, 63 patients (32%) were in CR and 134 (68%) were in partial remission (PR). The patients in CR had significantly longer overall survival (OS) from the day of ASCT compared with those in PR (P = .0015). Among the patients who received induction chemotherapy with vincristine, adriamycin, and dexamethasone (n = 162), the same difference in OS was seen between those in CR and those in PR before ASCT (P = .0016). CR after ASCT also predicted longer OS (P = .0135); however, patients with continued CR after ASCT had significantly higher OS after ASCT compared with patient with induced CR after ASCT who were in PR before ASCT (P = .0178). Multivariate analysis indicated that remission status pre-ASCT (CR vs PR) is a significant prognostic factor for predicting OS after ASCT (P = .012, Cox proportional hazard analysis; odds ratio = 2.83; 95% confidence interval = 1.25 to 6.37). We conclude that patients with MM who are in CR before ASCT have a better OS than those in PR before ASCT. Continued CR after ASCT may be an important prognostic factor as well. Our findings suggest that the development of more effective induction regimens, including novel antimyeloma agents to improve initial response, should be pursued to enhance clinical benefits post-ASCT.
对于65岁以下新诊断的多发性骨髓瘤(MM)患者, upfront高剂量清髓性化疗后进行单次自体干细胞移植(ASCT)是标准治疗方法。由于诱导化疗后的疾病状态存在差异,我们评估了ASCT前疾病状态的预后影响,尤其是在初始化疗敏感的患者中。我们回顾性分析了纳入韩国多发性骨髓瘤工作组基于网络注册系统(www.myeloma.or.kr)的初始化疗敏感的MM患者(≥部分缓解[PR])。在1996年11月至2007年1月期间,197例MM患者(中位年龄53岁)接受了诱导化疗,随后进行单次ASCT。所有患者在仅用美法仑(Mel)预处理后接受外周血干细胞(PBSC)支持。在本研究中,无论免疫固定结果如何,我们将那些检测不到M蛋白的患者视为完全缓解(CR)。从诊断之日起的中位随访时间为29.2个月(范围5.4至103.8个月),从ASCT之日起为22.4个月(范围0.4至96.0个月)。在ASCT前,63例患者(32%)处于CR,134例(68%)处于部分缓解(PR)。与PR患者相比,CR患者从ASCT之日起的总生存期(OS)显著更长(P = 0.0015)。在接受长春新碱、阿霉素和地塞米松诱导化疗的患者(n = 162)中,ASCT前CR患者与PR患者之间的OS也存在相同差异(P = 0.0016)。ASCT后的CR也预示着更长的OS(P = 0.0135);然而,ASCT后持续CR的患者与ASCT后诱导CR但ASCT前处于PR的患者相比,ASCT后的OS显著更高(P = 0.0178)。多变量分析表明,ASCT前的缓解状态(CR与PR)是预测ASCT后OS的重要预后因素(P = 0.012,Cox比例风险分析;比值比 = 2.83;95%置信区间 = 1.25至6.37)。我们得出结论,ASCT前处于CR的MM患者比ASCT前处于PR的患者具有更好的OS。ASCT后持续CR也可能是一个重要的预后因素。我们的研究结果表明,应寻求开发更有效的诱导方案,包括新型抗骨髓瘤药物以改善初始反应,以提高ASCT后的临床益处。