Clinical Significance Of Peripheral Blood T Lymphocyte Subsets And Circulation Plasma Cells In Patients With Newly Diagnosed Multiple Myeloma

Part One Prognostic impact of peripheral blood T lymphocyte subsets in patients with newly diagnosed multiple myelomaObjectiveMultiple myeloma(MM)is a malignant clonal plasma cell proliferative disease with heterogeneous clinical manifestations and prognosis.An active role for the immune system in controlling the malignant plasma cell clone in multiple myeloma(MM)has been investigated for many years,and abnormalities in populations of T cells have been consistently described in patients with MM.However,the studies on the correlations of T lymphocyte components in peripheral blood with patients' outcome were still limited.This study was retrospectively investigated the expression of T lymphocyte subsets in patients with newly diagnosed multiple myeloma(NDMM)by multi-parameter flow cytometry(MFC),and evaluated the prognostic value of T-cell abnormality in patients.MethodA total of 113 patients with NDMM at diagnosis between December 2012 to October 2016 in our center were studied.Pretreated multiparameter peripheral blood flow cytometry were applied to quantitate the components of the T lymphocyte subsets in number,including CD4+cell,CD8+cell,and CD4/CD8 ratio,to evaluate prognostic values of abnormal distributions of T cells in patients with MM at diagnosed.Result1.The median age of all the 113 patients with NDMM was 60 years(range,34-81),and the median follow-up time was 24.0(range,2.5-60)months.At the end of follow-up time,35 patients(30.1%)died and 68 patients(60.2%)relapsed or progressed,with an estimated median OS of 49.0 months and a median PFS of 22.5(95%CI 16.5-28.5)months,respectively.The 2-year OS and PFS rates in the whole cohort were 77%and 45%,respectively.The median absolute counts of CD4+T cell in the current cohort were 0.41(range,0.04-2.26)×10/L.The median ratio of CD4/CD8 in this cohort was 1.40(range,0.20-5.10).2.Patients' clinical characteristics according to the level of CD4+T cells:The optimal cutoff of CD4+cell count to predict the inferior survival of NDMM patients that calculated by Cutoff Finder was 0.5×109/L.In patients with CD4+cell count>0.5×109/L,hemoglobin(HB)and blood platelet count(BPC)levels were higher,while levels of ?2-microglobulin(?2-MG),LDH,ferritin(FER),blood urea nitrogen(BUN)and serum creatinine(sCr)were decreased.Among them,levels of HB,BPC,?2-MG and BUN were significantly different between two groups of patients(p=0.008,0.004,0.019,and 0.011,respectively).3.Association between the T lymphocyte subsets and the prognosis:1)The normal level of CD4+T cells in our center is greater than 30%.Patients with the percentage of CD4+cell less than 30%showed a shorter median OS(28 months vs.not reached,p=0.002)and worse 2-year OS rate(56%vs,82%),as well as a inferior median PFS(14 months vs.24 months,p=0.009)and 2-year PFS rate(24%vs.50%).2)The normal level of CD8+T cells in our center is less than 30%.Patients with the percentage of CD8+T cell more than 30%showed an unfavorable OS(40 months vs.not reached,p=0.032)and PFS(18 months vs.27 months,p=0.050),as well as lower 2-year OS rate(66%vs.83%)and 2-year PFS rate(34%vs.51%).3)The optimal cutoff of CD4+ cell count to predict the inferior survival of NDMM patients that calculated by Cutoff Finder was 0.5×109/L.Patients with absolute counts of CD4+T cell less than 0.5×109/L aforementioned showed a inferior OS(49 months vs.not reached,p=0.039)and PFS(18.0 months vs.32.5 months,p=0.010)than the patients with higher counts,as well as the worse 2-year OS rate(72%vs.85%)and 2-year PFS rate(39%vs.55%).4)The optimal cutoff of CD4/CD8 to predict the inferior survival of NDMM patients that calculated by Cutoff Finder was 0.7.The median OS of the patients with the lower level of ratio than 0.7 or not were 14.0 months and 49.0 months,with the 2-year OS rates of 34%and 82%,respectively(p<0.001).Moreover,the median PFS in 2 groups of patients with different levels of CD4/CD8 ratio were 10.0 months vs.24.0 months,with the 2-year PFS rates of 14%and 48%,respectively(p=0.015).5)The univariate analysis for OS and PFS:In the univariate analysis for OS,the risk of death increased in the patients with lower level of absolute count of CD4+T cell(<0.5×109/L,HR 2.149,95%CI 1.020-4.528,p=0.044)and lower ratio of CD4/CD8(<0.7,HR 3.810,95%CI 1.718-8.451,p=0.001).Among the traditional prognostic factors,higher LDH level(?271U/L,HR 4.095,95%CI 1.804-9.293,p=0.001),lower HB level(<100g/L,HR 2.214,95%CI 1.005-4.879,p=0.049),and higher ?2-MG level(?5.5mg/L,HR 2.262,95%CI 1.106-4.624,p=0.025)were adverse factors that increased the death risk in our cohort.With respect to the PFS,lower level of CD4+T cell count(HR 1.944,95%CI 1.155-3.272,p=0.012)and lower CD4/CD8 ratio(HR 2.265,95%CI 1.148-4.468,p=0.018)were also the unfavorable factors in the univariate analysis,while higher levels of ferritin(FER?322?g/L,HR 2.066,95%CI 1.173-3.640,p=0.012)and plasma cells(PCs?30%,HR 1.626,95%CI 1.001-2.647,p=0.050)were unfavorable clinical factors for inferior PFS.6)The COX multivariate analysis for OS and PFS:In the multivariate analysis,lower CD4/CD8 ratio was identified as an independent adverse prognostic factor for both OS(HR 2.756,95%CI 1.208-6.287,p=0.016)and PFS(HR 2.203,95%CI 0.999-4.858,p=0.050).Among clinical laboratory indicators,higher LDH level(HR 3.134,95%CI 1.355-7.252,p=0.008)was identified as an independent unfavorable prognostic factor for OS,while higher ferritin level(HR 2.255,95%CI 1.253-4.061,p=0.007)was an independent predictor for inferior PFS.Lower level of CD4+T cell was identified as an independent inferior predictor for PFS(HR 1.957,95%CI 1.070-3.582,p=0.029),but there was no significant in OS in multivariate analysis(HR 1.810,95%CI 0.815-4.021,p=0.145).ConclusionWe comprehensively analyzed the levels of T lymphocyte subsets and CD4/CD8 ratios in MM at diagnosed.These results showed that the level of T lymphocyte subsets was related to the characteristics and degree of MM,and patients with lower CD4/CD8 ratios had less survival rates.It suggested that T lymphocyte subsets were correlated with patients' clinical indicators and were important prognostic factors for patients with MM at diagnosed.Part Two Clinical Significance of peripheral blood circulation plasma cells in patients with newly diagnosed multiple myelomaObjectiveTo investigate the clinical significance of circulating plasma cell levels in patients with multiple myeloma(MM).MethodsA total of 72 patients with NDMM at diagnosis between October 2015 to June 2017 in our center were studied.The peripheral blood circulation plasma cell(CPC)level was detected by flow cytometry,and its correlation with clinical stages,initial diagnostic laboratory indexes and its influence on patients' survival were discussed.ResultsThe median age of all the patients with NDMM was 63(range,43-84)and the median follow-up time was 16.0(range,2-30)months.Among them,the circulating plasma cells were positive in 39 cases(54.1%)and 33 cases(45.9%)were negative.In patients with CPC+,?2-microglobulin(?2-MG),blood urea nitrogen(BUN),ferritin(FER)and plasma cells were higher,while levels of blood platelet count(BPC)were significantly decreased(p<0.05).The patients with CPC+ had a positive correlation with the clinical stages of the patient,which increased with the increase of CPC+,and there is a statistical difference between the DS and ISS(p<0.05).The results of survival analysis suggested that patients with CPC-and CPC+ showed a similar median OS(not reached vs.not reached,p=0.089)and 1-year OS rate(97%vs.79%,p=0.042),as well as a similar median PFS(26 months vs.15.5 months,p=0.056)and 1-year PFS rate(74%vs.56%,p=0.075).ConclusionThe level of circulating plasma cells is related to the severity of the initial diagnosis of MM patients,and the prognosis of negative patients is significantly better than that of the positive patients,which is of great significance for the prognosis evaluation and management of the initial diagnosis.