【摘要】 目的探讨临床特征、实验室指标、治疗方案对多发性骨髓瘤(MM)预后的意义。方法选取2000年1月—2012年3月北京积水潭医院血液科确诊的初治MM并行化疗、有完整随访资料的患者202例为研究对象,均采用化疗,42例合并放疗。记录患者的性别、年龄、分型、有无重度贫血、血β2微球蛋白水平、C反应蛋白水平、有无低蛋白血症、血钙水平、乳酸脱氢酶水平、骨髓浆细胞比例、骨病分级(MBD分级)、美国东部肿瘤协作组体力状况评分(ECOG评分)、有无复杂核型(G显带核型分析)、有无淀粉样变、有无肾损伤、有无截瘫及是否达到完全缓解(CR)、有无沙利度胺维持治疗(治疗≥6个月)。随访至2015年3月,随访时间1.0~180.0个月。采用多因素Cox比例风险回归分析各因素及采用生存曲线分析DS分期、ISS分期与MM患者总生存期(OS)、无进展生存期(PFS)的相关性;19例患者在确诊后6个月内死亡,采用多因素Logistic回归分析早期死亡的影响因素;根据OS和PFS的共同影响因素及ISS分期对患者进行危险因素分层,分为高危组、中危组、低危组,分析不同危险因素分层患者的预后。结果 202例MM患者中53例(26.2%)达到CR,96例(47.5%)达到非常好的部分缓解(VGPR),29例(14.4%)达到部分缓解(PR),总有效率为88.1%。截至随访时间死亡120例。1、3、5、10年生存率分别为80.7%、70.6%、36.1%、7.6%。OS为1.0~180.0个月,中位OS为51.0个月;PFS为1.0~91.0个月,中位PFS为38.0个月。多因素Cox比例风险回归分析结果显示,年龄、重度贫血、低蛋白血症、复杂核型、淀粉样变、截瘫、沙利度胺维持治疗与OS有回归关系(P<0.05);年龄、重度贫血、复杂核型、截瘫、沙利度胺维持治疗与PFS有回归关系(P<0.05)。不同DS分期患者OS比较,差异无统计学意义(χ~2=1.710,P>0.05)。不同DS分期患者PFS比较,差异有统计学意义(χ~2=12.222,P<0.05)。不同ISS分期患者OS、PFS比较,差异有统计学意义(χ~2值分别为15.037及32.222,P<0.05)。单因素分析结果显示,有无重度贫血〔32%(8/25)与6.2%(11/177),χ~2=0.512,P=0.039〕、有无淀粉样变〔66.7%(4/6)与7.7%(15/196),χ~2=11.460,P=0.007〕患者早期死亡率比较,差异有统计学意义。多因素Logistic回归分析结果显示,淀粉样变是早期死亡的独立影响因素〔β=2.178,SE=0.915,Waldχ~2=5.669,P=0.017,OR=8.826,95%CI(1.470,53.002)〕。不同危险因素分层患者OS、PFS比较,差异有统计学意义(P<0.001)。结论 MM患者预后影响因素复杂多样,高龄、合并重度贫血、低蛋白血症、复杂核型、淀粉样变、截瘫的患者预后较差,沙利度胺维持治疗的患者可获得更长的生存期,ISS分期较DS分期更有预测预后的意义,合并淀粉样变患者早期死亡风险大。根据OS和PFS的共同影响因素及ISS分期对患者进行危险因素分层对预测患者预后有意义。更多还原

【Abstract】 Objective To investigate the significance of clinical features,laboratory indexes and treatment regimen on the prognosis of multiple myeloma( MM). Methods Enrolled 202 patients who were newly diagnosed with MM and had complete follow- up data in the Department of Hematology of Beijing Jishuitan Hospital From January 2000 to March 2012. All the patients underwent chemotherapy. Among them,42 patients underwent chemoradiotherapy. The observed indexes included gender,age,typing, having severe anemia or not, blood level of β2- microglobulin, C- reactive protein level, having hypoalbuminemia or not,blood calcium level,lactic dehydrogenase level,proportion of bone marrow plasma cells,bone disease grading( MBD grading), ECOG score, complex karyotype( G banding karyotype analysis), amyloidosis, renal injury,paraplegia,whether treatment achieved complete remission( CR) and whether thalidomide maintenance therapy was conducted or not( treatment duration≥6 months). Follow- up ended in March 2015,lasting for 1. 0- 180. 0 months. Multivariate Cox proportionnal hazards regression analysis and survival curves analysis were conducted on the correlation of DS staging,ISS staging and other factors with the overall survival( OS) and progression free survival( PFS) of MM patients. A total of 19 patients died6 months after diagnosis,and multivariate Logistic regression analysis was employed to investigate influencing factors for early death. According to common influencing factors for OS and PFS and ISS staging,the patients were divided into three groups: high risk group,average risk group and low risk group. The prognosis of the three groups was analyzed. Results Among 202 MM patients,53( 26. 2%) patients had CR; 96( 47. 5%) had very good partial response( VGPR); 29( 14. 4%) patients had partial remission( PR); the overall effective rate was 88. 1%. By the end of follow- up,120 patients died. One- year,three-year,five- year and ten- year survival rates were 80. 7%,70. 6%,36. 1% and 7. 6% respectively. OS was 1. 0- 180. 0months,and median OS was 51. 0 months; PFS was 1. 0- 91. 0 months,and median PFS was 38. 0 months. Multivariate Cox proportional hazards regression analysis showed that age,severe anemia,hypoalbuminemia,complex karyotype,amyloidosis,paraplegia and thalidomide maintenance treatment had regression relation with OS( P < 0. 05); age,severe anemia,complex karyotype,paraplegia and thalidomide maintenance treatment had regression relation with PFS( P < 0. 05). Patients with different DS stages were not significantly different in OS( χ~2= 1. 710, P > 0. 05). Patients with different DS stages were significantly different in PFS( χ~2= 12. 222,P < 0. 05). Patients with different ISS stages were significantly different in OS and PFS( χ~2values were 15. 037 and 32. 222,P < 0. 05). Univariate analysis showed that patients with severe anemia 〔32%( 8/25) vs. 6. 2%( 11 /177),χ~2= 0. 512,P = 0. 039〕and amyloidosis〔66. 7%( 4 /6) vs. 7. 7%( 15 /196),χ~2= 11. 460,P= 0. 007〕were significantly different from patients without them. Multivariate Logistic regression analysis showed that amyloidosis was an independent influencing factor for early death 〔β = 2. 178,SE = 0. 915,Wald χ~2= 5. 669,P = 0. 017,OR = 8. 826,95% CI( 1. 470,53. 002) 〕. Patients with different risk gradings were significantly different in OS and PFS( P < 0. 001).Conclusion Influencing factors for the prognosis of MM patients are complex and diverse,including advanced age,combined severe anemia, hypoproteinemia, complex karyotype, amyloidosis and paraplegia. Patients receiving thalidomide maintenance treatment have longer survival time. ISS staging has greater significance than DS staging in the prognosis. Patients combined with amyloidosis have higher risk for early death. Risk grading by common influencing factors for OS and PFS and ISS staging are of significance in the prognosis of patients.更多还原