| ObjectiveMultiple myeloma(MM)is a malignant clonal plasma cell proliferative disease with heterogeneous clinical manifestations and prognosis.Flow cytometry is a convenient,sensitive,rapid and accurate detection for the expression of immunophenotype on plasma cells.This study was retrospectively investigated the expression of imnunophenotype of bone marrow plasma cells in patients with newly diagnosed multiple myeloma(NDMM)by multi-parameter flow cytometry(MFC),and evaluated the correlation between the immunophenotype and patients' outcome.MethodA total of 152 patients with NDMM at diagnosis between September 2011 and December 2016 in our center were studied.The expressions of immunophenotype(CD20,CD200,CD 117,CD81,CD27 and CD28)on the bone marrow malignant plasma cells of the patients were detected by multi-parameter flow cytometer.Patients' clinical and biological characteristics were also studied to evaluate the correlations between the expressions of immunophenotype and prognosis,efficacy and risk factor of early death.Result1.The median onset age of all the 152 patients with NDMM was 62 years(range,34-80),and the median follow-up time was 16.0(range,1.0-65.5)months.The positive expression rate of CD20,CD200,CD81,CD27 CD117and CD28 were 28.8%(36/125),69.6%(96/138),75.5%(40/53),68.7%(90/131),39.0%(48/123)and 42.6%(29/68),respectively.2.Association between the expression of the immunophenotype and the prognosis:1)The median overall survival(OS)of CD200+ and CD200-patrients were 48 months and not reached with the significant difference(p=0.049),while the median progression-free survival time(PFS)were 22.5 and 27 months(p=0.322).The 1-year OS rates of the 2 groups were 81%and 92%(p=0.066),and the 1-year PFS rates were 72%and 75%,respectively(p=0.203).2)The median OS of CD 117+ and CD 117-patients were both not reached(p=0.263),while the median PFS were 24 and 19 months(p=0.146),respectively.The 1-year OS and PFS rates were 81%vs.84%(p=0.617)and 76%65%(p=0.307),respectively.3)The median OS of CD20+ and CD20-patients were not reached 42 months(p=0.113)with 1-year OS rates of 85%and 84%(p=0.331).Meanwhile,the median OS of CD81+ and CD81-patients were both not reached(p=0.489)with 1-year OS rates of 76%and 79%(p=0.641).4)The median PFS of CD27+ and CD27-patients were 23 and 17.5 months(p=0.141)with 1-year PFS rates of 70%and 58%(p=0.213).Meanwhile,the median PFS of CD28+ and CD28-patients were 19.0 and 24.5 months(p=0.489)with 1-year PFS rates of 64%and 79%(p=0.257).5)The patients with the immunophenotype of CD200-CD117+ and CD200+CD117-were 22 cases(28.9%)and 54 cases(71.1%),respectively.The OS of the 2 groups were not reached and 30.5 months(p=0.058),while PFS were not reached and 19 months(p=0.063).The 1-year OS and PFS were 95%vs.83%(p=0.056)and 83%vs.66%(p=0.166),respectively.6)The patients with the CD200-CD27+ and CD200+CD27-immunophenotype were 22 cases(48.9%)and 23 cases(51.1%).The OS of the 2 groups were not reached and 24 months(p=0.022),while the PFS were not reached and 17.5 months(p=0.014),both the differences had statistic significances.The 1-year OS and PFS were 94%vs.80%(p=0.102)and 86%vs.60%(p=0.038).7)Among above immunophenotype investigated,CD200 was the only immunophenotype closed to significant difference(HR 2.495,95%CI 0.971-6.409,p=0.058)in univariate cox regression analyses for survival.However,the univariate cox regression analyses for PFS showed no correlation between immunophenotype and the prognosis.A multivariate analysis showed LDH was the unique unfavorable factor for both OS(HR 3.452,95%CI 1.272-9.366,p=0.015)and PFS(HR 2.671,95%CI 1.241-5.750,p=0.012).3.Correlation between the expression of the immunophenotype and the patients'clinical characteristics:there were negative correlations between CD200 expression and blood platelets count,as well as CD117 expression and LDH level(r=-0.200,p=0.021;r=-0.212,p=0.025).The patients with CD200-/CD27+immunophenotype had higher hemoglobin count and album level(p=0.062,p=0.025),but lower plasma cells proportion in bone marrow than the patients with CD200+/CD27-immunophenotype(p=0.046).4.Correlation between the expression of the immunophenotype and the biological characteristics of the disease:there were positive correlations between plasma cells proportion by morphological test and MFC(r=0.592,p<0.001).The correlation between CD200 and CD117 expression was negative(r=-0.243,p=0.007).CD200 expression had positive correlation with lq21 amplification(r=0.200,P=0.0387);CD20 expression also had positive correlation with t(11;14)(r=0.221,p=0.088),but negative correlation with del(13ql4),(r=-0.290,p=0.021).The correlation between CD27 expression and t(4;14)was also negative(r=-0.241,p=0.017).5.Response analyses:AUC of ROC curve for not achieving PR/VGPR according to CD20 and ?2 microglobulin was>0.7 and p?0.05,so the combination of the 2 variables was the prediction for the response of the initial therapy.6.Analyses for early death:AUC of ROC curve for early death according to CD28 and ISS/?2 microglobulin was>0.7 and p?0.05,so the combination of CD28 expression and the 2 factors were the predictions of high risk for early death.ConlusionImmunophenotypic evaluation of the patients' bone marrow plasma cells by multiple flow cytometry had shown significances in prognostic assessment,response prediction and screening for high risk factors of early death,MFC Immunophenotype plays a vital role in MM patient's management. |
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