多发性骨髓瘤复发伴髓外病变患者的临床特点及预后分析

Clinical features and prognosis analysis of extramedullary disease in relapsed multiple myeloma

目的探讨多发性骨髓瘤（MM）复发伴髓外病变患者的临床特点及预后危险因素。方法回顾性分析2008年8月至2014年9月北京积水潭医院收治的41例MM复发时伴髓外病变患者，其中20例的髓外病变生长在骨外器官及软组织中（骨外髓外病变组），21例仅生长在骨组织旁（骨旁髓外病变组）。分析髓外病变的临床特点、治疗效果、生存情况及影响预后的因素。结果与骨旁髓外病变组相比，骨外髓外病变组乳酸脱氢酶升高（≥250IU／L）、染色体异常、13q14缺失和17p13缺失更为常见[50．0％（10／20）比19．0％（4／21），46．7％（7／15）比7．7％（1／13），75．0％（9／12）比27．3％（3／11），41．7％（5／12）比0．0％（0／11）]（P〈0．05）。骨外髓外病变组的总体反应率为35．0％（7／20），明显低于骨旁髓外病变组的76．3％（16／21）（P=0．009）。所有患者中位总生存时间为36个月[95％置信区间（CI）：24．3—47．7]，复发后中位生存时间仅为9个月（95％CI：5．3～12．7）；骨外髓外病变组患者复发后中位生存时间明显低于骨旁髓外病变组（5个月比12个月，P=0．001）。Log—rank单因素分析显示，存在骨外髓外病变（P=0．001）、血钙1〉2．75mmol／L（P=0．018）、国际分期体系分期Ⅱ和Ⅲ期（P=0．008）、乳酸脱氢酶≥250IU／L（P=0．043）、复发后治疗无效（P〈0．001）为预后不良指标。Cox多因素回归分析显示，存在骨外髓外病变（风险比=3．822，95％CI：1．543～9．465）及复发后治疗无效（风险比=6．251，95％CI：2．442—15．996）为影响髓外病变复发后生存期的独立危险因素。结论MM复发伴骨外髓外病变较骨旁髓外病变预后差，需要寻求更加积极有效的治疗方案。

Objective To investigate clinical features and risk factors of extramedullary disease（EMD） in relapsed multiple myeloma. Methods Totally 41 cases of relapsed multiple myeloma complicated with EMD from August 2008 to September 2014 in Beijing Jishuitan Hospital were retrospectively analyzed, including 20 patients with myeloma in extraosseous organs and soft tissues（extraosseous EMD group） and 21 patients with myeloma in adjacent tissue（ osseous EMD group）. Clinical features, treatment effect, survival time and prognostic factors were analyzed. Results Elevated lactate dehydrogenase （ ≥ 250 IU/L） , chromosomal abnormalities, 13q14 deletion and 17p13 deletion were more eommom in extraosseous EMD group than those in osseous EMD group [ 50.0% （10/20） vs 19.0% （4/21）, 46.7% （7/15） vs 7.7% （1/13）, 75.0% （9/12） vs 27.3% （3/11）, 41.7% （5/12） vs 0. 0% （0/11） ] （P 〈 0. 05）. The overall response rate in extraosseous EMD group was significantly lower than that in osseous EMD group[35.0% （7/20） vs 76. 3% （ 16/21 ） 1 （P =0. 009）. The median overall survival time（OS） in 41 cases of multiple myeloma was 36 months[95% confidence interval（CI） ： 24. 3-47.7 ], the median OS after EMD relapsed was only 9 months （95 % CI： 5.3-12. 7 ）. The median OS after relapse in extraosseous EMD group was significantly shorter than that in osseous EMD group（5 months vs 12 months, P = 0. 001 ）. Log-rank univariate analysis showed that extraosseous EMD relapse （ P = 0. 001 ）, serum calcium ≥ 2. 75 mmol/L （P =0. 018）, ISS stage Ⅱ and Ⅲ （P =0 008）, lactate dehydrogenase≥250 IU/L（P =0. 043） and no response to chemotherapy after relapse （ P 〈 0. 001 ） were poor prognostic factors. Cox multivariate analysis showed that extraosseous EMD relapse[ hazard ratio（HR） = 3. 822,95% CI： 1. 543-9. 465 ] and no response to chemotherapy after relapse （ HR = 6. 251,95 % CI： 2. 442-15. 996 ） were independent risk factors for predicting the survival after EMD relapse. Conclusion Extraosseous myeloma relapse has poorer prognosis than osseous myeloma.