流式细胞术对多发性骨髓瘤患者微小残留病的检测
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摘要
目的:应用流式细胞术(FCM)检测多发性骨髓瘤(MM)患者微小残留病(MRD)水平,探讨MRD与预后的关系。方法:统计2013—2016年我院血液肿瘤科接受化疗达完全缓解(CR)的MM患者39例,分析其临床特征及MRD水平。结果:多因素分析显示,乳酸脱氢酶≥230U/L(P=0.002)、β_2微球蛋白≥3.5mg/L(P=0.002)、血肌酐≥177mmol/L(P=0.047)是影响MM患者预后的独立危险因素。MM患者达到CR后首次监测MRD水平,14例MRD阳性患者(MRD≥0.01%)与25例MRD阴性患者(MRD<0.01%)间复发率存在显著差异(P=0.008)。对MRD阳性组患者进行危险分层发现,较高的MRD水平(MRD≥0.1%)具有更高的复发风险(P=0.036)。动态监测MRD水平结果显示,持续MRD阳性患者与持续MRD阴性患者间的无复发生存期存在显著差异(P=0.035)。结论:FCM监测MRD水平对判断MM患者预后有重要意义。
Objective:To detect minimal residual disease in multiple myeloma(MM)patients by flow cytometry(FCM),and to discuss the relationship between minimal residual disease(MRD)and prognosis.Methods:The patients with receiving chemotherapy whose bone marrow was reached to complete remission were collected in our hospital from 2013 to 2016.Results:Multivariate analysis showed that LDH ≥230 U/L(P=0.002),β_2 microglobulin ≥3.5 mg/L(P=0.002) and serum creatinine level ≥177 mmol/L(P=0.047) are predict factors for prognosis in MM patients.First MRD level after reaching CR,there was a significant difference of recurrence rate between 14 MRD-positive patients(MRD≥0.01%) and 25 MRD-negative patients(MRD<0.01%)(P=0.008).In patients with MRD-positive group, higher MRD level(MRD≥ 0.1%) had a higher risk of recurrence(P=0.036).After dynamically monitoring MRD levels,the result showed that there was a significant difference in progression free survival between patients with persistent MRD-positive and patients with persistent MRD-negative(P=0.035).Conclusion:The monitoring of MRD by FCM had an important value on judging the prognosis.
Objective:To detect minimal residual disease in multiple myeloma(MM)patients by flow cytometry(FCM),and to discuss the relationship between minimal residual disease(MRD)and prognosis.Methods:The patients with receiving chemotherapy whose bone marrow was reached to complete remission were collected in our hospital from 2013 to 2016.Results:Multivariate analysis showed that LDH ≥230 U/L(P=0.002),β_2 microglobulin ≥3.5 mg/L(P=0.002) and serum creatinine level ≥177 mmol/L(P=0.047) are predict factors for prognosis in MM patients.First MRD level after reaching CR,there was a significant difference of recurrence rate between 14 MRD-positive patients(MRD≥0.01%) and 25 MRD-negative patients(MRD<0.01%)(P=0.008).In patients with MRD-positive group, higher MRD level(MRD≥ 0.1%) had a higher risk of recurrence(P=0.036).After dynamically monitoring MRD levels,the result showed that there was a significant difference in progression free survival between patients with persistent MRD-positive and patients with persistent MRD-negative(P=0.035).Conclusion:The monitoring of MRD by FCM had an important value on judging the prognosis.
引文
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[11] Paiva B,van Dongen JJ,Orfao A.New criteria for resPonse assessment:role of minimal residual disease in multiPle myeloma [J].Blood,2015,125(20):3059-3068.
[12] Paiva B, Cedena MT, Puig N,et al.Minimal residual disease monitoring and immune Profiling in multiPle myeloma in elderly Patients[J].Blood,2016,127(25):3165-3174.
[2] Mey UJ,Leitner C,Driessen C,et al.ImProved survival of older Patients with multiPle myeloma in the era of novel agents[J].Hematol Oncol,2016,34(4):217-223.
[3] Rawstron AC,Child JA,de Tute RM,et al.Minimal residual disease assessed by multiParameter flow cytometry in multiPle myeloma: imPact on outcome in the Medical Research Council Myeloma IX Study[J].J Clin Oncol,2013,31(20):2540-2547.
[4] Rawstron AC,Gregory WM,de Tute RM,et al.Minimal residual disease in myeloma by flow cytometry: indePendent Prediction of survival benefit Per log reduction[J].Blood,2015,125(12):1932-1935.
[5] 中国医师协会血液科医师分会, 中华医学会血液学分会, 中国医师协会多发性骨髓瘤专业委员会.中国多发性骨髓瘤诊治指南(2017年修订)[J].中华内科杂志,2017,56(11):866-870.
[6] GreiPP PR,San Miguel J,Durie BG,et al.Intemational staging system for multiPle myeloma[J].J Clin Oncol,2005,23(15):3412-3420.
[7] Younes M,Hachfi H,Hammouda F,et al.Survival Prognosis factors in multiPle myeloma[J].Tunis Med,2014,92(6):399-405.
[8] 卢力丽,王伟,赵洪国,等.多发性骨髓瘤214例临床分析[J].中华临床医师杂志,2014,8(23):4204-4207.
[9] Puig N,Sarasquete ME,Balanzategui A,et al.Critical evaluation of ASO RQ-PCR for minimal residual disease evaluation in multiPle myeloma.A comParative analysis with flow cytometry[J].Leukemia,2014,28(2):391-397.
[10] Martinez-LoPez J,Lahuerta JJ,PePin F,et al.Prognostic value of deeP sequencing method for minimal residual disease detection in multiPle myeloma[J].Blood,2014,123(20):3073-3079.
[11] Paiva B,van Dongen JJ,Orfao A.New criteria for resPonse assessment:role of minimal residual disease in multiPle myeloma [J].Blood,2015,125(20):3059-3068.
[12] Paiva B, Cedena MT, Puig N,et al.Minimal residual disease monitoring and immune Profiling in multiPle myeloma in elderly Patients[J].Blood,2016,127(25):3165-3174.