Analysis of influencing factors and prognosis of secondary extramedullary disease in multiple myeloma
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摘要: 目的 探讨初诊无伴髓外病变的多发性骨髓瘤(MM)患者继发髓外病变(EMM)的影响因素，并分析对预后的影响。方法 回顾性分析厦门大学附属东南医院2018年1月—2021年12月收治的123例初诊无EMM的MM患者临床资料，根据是否继发EMM分为EMM组(n=35)和no-EMM组(n=88)。采用单因素和logistic多因素分析EMM发生的影响因素，采用Kaplan-Meier法进行生存分析EMM对预后的影响，并进行log-rank检验。结果 123例初诊无EMM的MM患者中35例继发EMM，发生率为28.46%。35例EMM患者中骨旁EMM 9例、髓外EMM 26例，9例骨旁EMM患者中胸肋骨4例、椎体3例、骨盆2例，26例髓外EMM患者中皮肤及软组织13例、胸膜6例、淋巴结4例、纵隔2例、肾上腺1例。EMM发生时间为4~14个月，中位时间7个月。与no-EMM组比较，EMM组DS分期Ⅲ期、ISS分期Ⅲ期、血白蛋白＜35 g/L、血红蛋白＜85 g/L、β2-微球蛋白≥5.5 mg/L、血钙≥2.65 mmol/L、溶骨性病变≥3处、FISH检测高危、治疗效果无缓解比例更高(P＜0.05)。多因素分析结果发现DS分期Ⅲ期(OR=3.367、95%CI 1.205~9.405)、ISS分期Ⅲ期(OR=4.563、95%CI 1.645~11.426)、血钙≥2.65 mmol/L(OR=3.142、95%CI 1.170~8.326)、FISH检测高危(OR=4.251、95%CI 1.403~12.880)、治疗效果无缓解(OR=2.804、95%CI 1.043~7.538)是EMM发生的独立危险因素。123例初诊无EMM的MM患者中位随访时间为26.5个月，EMM组中位OS为16.5个月，no-EMM组中位OS为36个月。Log-rank分析EMM组和no-EMM组中位OS差异有统计学意义(χ2=7.365，P=0.007)。结论 DS分期Ⅲ期、ISS分期Ⅲ期、血钙≥2.65 mmol/L、FISH检测高危、治疗效果无缓解是MM患者继发EMM的独立危险因素，EMM患者总生存时间更差。Abstract: Objective To investigate the influencing factors of secondary extramedullary disease(EMM) in multiple myeloma(MM) and to analyze the influence on prognosis.Methods Clinical data of 123 newly diagnosed MM patients without EMM admitted to Dongnan Hospital Affiliated to Xiamen University from January 2018 to December 2021 were retrospectively analyzed, and they were divided into EMM group(n=35) and no-EMM group(n=88) according to whether they had secondary EMM. Univariate and logistic multivariate analysis were used to analyze the influencing factors of EMM occurrence, Kaplan-Meier method was used to analyze the impact of EMM on prognosis, and log-rank test was performed.Results Among 123 MM patients without EMM at first diagnosis, 35 had secondary EMM(28.46%). Among the 35 patients with EMM, there were 9 cases of paramedullary EMM, 26 cases of extramedullary EMM, 4 cases of thoracic rib involvement, 3 cases of vertebral body involvement, 2 cases of pelvis involvement, and 13 cases of skin and soft tissue involvement, 6 cases of pleura involvement, 4 cases of lymph nodes involvement, 2 cases of mediastinum involvement, and 1 case of adrenal gland involvement. The duration of EMM was from 4 to 14 months, with a median duration of 7 months. Compared with no-EMM group, DS stage Ⅲ, ISS stage Ⅲ, blood albumin < 35 g/L, hemoglobin < 85 g/L, β2-microglobulin≥5.5 mg/L, blood calcium≥2.65 mmol/L, osteolytic lesions≥3, FISH detection of high risk, the proportion of treatment effect without remission were higher(P < 0.05). The results of multivariate analysis showed that DS stage Ⅲ(OR=3.367, 95%CI 1.205-9.405), ISS stage Ⅲ(OR=4.563, 95%CI 1.645-11.426), blood calcium≥2.65 mmol/L(OR=3.142, 95%CI 1.170-8.326), FISH detection of high risk(OR=4.251, 95%CI 1.403-12.880) and no remission(OR=2.804, 95%CI 1.043-7.538) were independent risk factors for EMM. The median follow-up time of 123 MM patients without EMM was 26.5 months, the median OS was 16.5 months in the EMM group, and the median OS was 36 months in the no-EMM group. There was significant difference in median OS between EMM group and no-EMM group by log-rank analysis(χ2=7.365, P=0.007).Conclusion DS stage Ⅲ, ISS stage Ⅲ, blood calcium ≥2.65 mmol/L, high risk of FISH detection, and no remission of treatment effect were independent risk factors for secondary EMM in MM patients, and the overall survival time of EMM patients was worse.
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Key words:
- multiple myeloma /
- extramedullary lesions /
- prognostic factor
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表 1 EMM发生单因素分析
例 因素 EMM组
(n=35)no-EMM组
(n=88)统计值 P 因素 EMM组
(n=35)no-EMM组
(n=88)统计值 P 年龄/岁 56.02±6.64 53.68±6.08 1.897 0.063 血钙/(mmol/L) 4.314 0.038 ＜2.65 22 71 性别 0.184 0.668 ≥2.65 13 17 男 16 44 血肌酐/(μmol/L) 0.677 0.411 女 19 44 ＜177 25 69 亚型 ≥177 10 19 IgG 16 48 0.782 0.376 LDH/(U/L) 1.156 0.282 IgA 9 20 0.124 0.725 ＜220 27 75 IgD 2 1 2.205 0.195 ≥220 8 13 κ轻链 5 15 0.140 0.793 骨髓浆细胞比例/% 12.85±3.15 14.48±3.62 -1.707 0.090 λ轻链 2 1 2.205 0.195 不分泌型 1 3 0.024 0.876 核染色体 ＜0.001 0.090 DS分期 7.298 0.007 异常 6 15 Ⅰ~Ⅱ期 16 63 正常 29 73 Ⅲ期 19 25 溶骨性病变/处 4.996 0.025 ISS分期 5.515 0.019 ＜3 22 72 Ⅰ~Ⅱ期 15 58 ≥3 13 16 Ⅲ期 20 30 FISH 10.092 0.001 血白蛋白/(g/L) 5.959 0.015 无高危 20 74 ＜35 19 27 高危a 15 14 ≥35 16 61 治疗方法 2.685 0.443 血红蛋白/(g/L) 3.986 0.046 PI 19 51 ＜85 17 26 IMiD 12 31 ≥85 18 62 PI联合IMiD 1 4 β2-微球蛋白/(mg/L) 9.302 0.002 单化疗 3 2 治疗效果 9.724 0.002 ＜5.5 21 75 缓解 15 64 ≥5.5 14 13 无缓解 20 24 注：aFISH高危指荧光原位杂交(FISH)检测出del(17p)，t(4；14)，t(14；16)。 
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表 2 EMM发生多因素分析
因素 β SE Wald χ2 OR 95%CI P DS分期Ⅲ期 1.214 0.524 5.366 3.367 1.205~9.405 0.021 ISS分期Ⅲ期 1.519 0.635 5.722 4.563 1.645~11.426 0.010 血白蛋白＜35 g/L 0.307 0.641 0.230 1.360 0.387~4.772 0.631 血红蛋白＜85 g/L 0.398 0.522 0.580 1.488 0.535~4.142 0.446 β2-微球蛋白≥5.5 mg/L 0.720 0.658 1.196 2.054 0.566~7.456 0.274 血钙≥2.65 mmol/L 1.145 0.548 6.047 3.142 1.170~8.326 0.035 溶骨性病变≥3处 0.716 0.568 1.590 2.046 0.672~6.225 0.207 FISH检测高危 1.447 0.566 6.564 4.251 1.403~12.880 0.011 治疗效果无缓解 1.031 0.505 4.177 2.804 1.043~7.538 0.041
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