The Clinical And Prognostic Significance Of Minimal Residual Disease And Circulating Plasma Cells To The Patients With Multiple Myeloma By 10-color Flow Cytometry

Part Ⅰ:The clinical and prognostic significance of minimal residual disease to the patients with multiple myeloma by 10-color flow cytometryObjective:This study was designed to evaluate the prognostic significance of minimal residual disease(MRD)by 10-color flow cytometry to the patients with multiple myeloma(MM)after treatment.Methods:We analyzed 150 patients with MM at the First Affiliated Hospital of Soochow University from July 2015 to July 2017,and 102 patients with VGPR and above after treatment were enrolled this study.All the patients were diagnosed and the response were assessed by international myeloma working group(IMWG)criteria.The response evaluation and MRD detection were performed at 1 month after the end of the last induction therapy and 3 months,6 months,and 1 year after transplantation.10-color flow cytometry was used to detect MRD,and MRD negativity was defined when<20 clonal plasma cells were detected among 1,000,000 leukocytes(<0.002%).Results:The patients with MRD negativity(39.1%,34/87)after induction therapy had longer PFS than those patients with MRD positivity.(The median PFS were not reached vs 21 months,P=0.022);The median PFS were not reached in patients with MRD negativity among 1 year after autologous stem cells transplantation,(49.3%,34/69)and 18 months for the patients with MRD positivity(P<0.001).Moreover,Those patients attaining MRD negativity without CR after transplantation had significantly prolonged PFS compared to MRD-positive patients and similar PFS to MRD-negative patients in CR,even with R-ISS stage Ⅱ and Ⅲ,or with high-risk cytogenetics.By contrast,MRD-positive patients with CR or R－ISS stage Ⅰ had similar poor PFS to those less than CR or R-ISS stage Ⅱ and Ⅲ.According to the changes of MRD,the patients were divided into 4 groups:patients with MRD continued negativity,improved from being MRD positive to MRD negative,MRD continued positivity,transformed from being MRD negative to MRD positive.The two-year PFS of the four groups were 84%,81%,38%,0,respectively,P<0.001.Multivariate analysis showed that the level of MRD after induction therapy was an independent prognostic factor for PFS,P=0.002,HR=4.808(1.818,12.718).Conclusions:Patients with MRD negative after treatment is a better prognostic marker than CR or even the best marker.The ten-color flow cytometry can be used as an effective method for detecting MRD in clinical practice.Part Ⅱ:The clinical and prognostic signifncance of circulating plasma cells to the patients with multiple myeloma by 10-color flow cytometryObjective:This study was designed to evaluate the prognostic significance of circulating plasma cells(cPCs)by 10-color flow cytometry to the newly diagnosed multiple myeloma(MM)patients.Methods:74 newly diagnosed multiple myeloma seen at the First Affiliated Hospital of Soochow University from August 2016 to December 2017 were enrolled this study.All the patients had their PB evaluated for cPCs by 10-color flow cytometry before treatment.Survival analysis was performed by Kaplan-Meier method and differences assessed using the log rank test.Results:The median Progression-Free-Survival(PFS)for patients with cPCs(N=54,73%)was 2 years compared with not reached for patients without cPCs(N=20,27%),P=0.0375.The 2-year overall survival(OS)for patients with cPCs(N=54,73%)was 80%compared with 100%for patients without cPCs(N=20,27%),P=0.0751.Using a ROC analysis,(?)0.165%cPCs was considered as the optimal cutoff for defining high-risk disease.The median PFS for the patients with(?)0.165%cPCs(N=26,35%)was 17 months compared with not reached for those with<cPCs 0.165%(N=48,65%),P<0.001.The 2-year OS for the patients with(?)0.165%cPCs(N=26,35%)was 63%compared with 98%for those with<cPCs 0.165%(N=48,65%),P=0.001.In a multivariable analysis,the presence of>=0.165%cPCs was associated with shorter PFS and OS.Conclusions:This study indicated that Flow cytometry to detect cPCs is a valuable method for predicting prognosis of newly diagnosed MM.Future studies are needed to determine the significance to treatment.