Clinical Immune Research Of Multiple Myeloma Patients With Hypogammaglobulinemia

Objective Multiple myeloma(MM)is a monoclonal plasma cell proliferative disorder.Current treatment exerts tremendous effects on the immune system of MM patients,result in the hypogammaglobulinemia.However,the role of hypogammaglobulinemia in MM is unknown.In addition,the Tfh cells play an important role on the B cell differentiation into plasma cell.While the role of Tfh cells in MM is still unknown.Therefore,we conducted this study to describe the prognosis role of IgG<5 g/L in MM with hypogammaglobulinemia patients and unveil the clinical significance of Tfh subsets in MM.Method1.We adopted a previously published online questionnaire of current clinical practices regarding the management of hypogammaglobulinemia caused by hematological malignancies and then distributed the questionnaire to 52 hematologists in China via WeChat mobile software and analyzed the data.2.Then MM patients(295)were retrospectively analyzed between January 2012 and 2020 in Zhejiang Provincial People’s Hospital,Hangzhou Medical College.MM patients with immunoglobulin(Ig)G<5 g/L of were defined as hypogammaglobulinemia patients.The care of these patients and the prognostic role of IgG<5 g/L were analyzed.3.The peripheral blood cells of MM patients were performed in the flow cytometry and then the subsets of Tfh cells analyzed by Kaluza software,including CXCR3+CCR6-Tfh1 cell,CXCR3-CCR6-Tfh2 cell and CXCR3-CCR6+Tfh17 cell.Results1.Questionnaire data revealed that there are no specific criteria for selecting hypogammaglobulinemia patients using prophylactic Ig replacement.Moreover,the total 48 hematologists differed significantly in their responses to the starting dose,frequency,and target Ig level.2.Forty-five of 295 MM patients with IgG<5 g/L were defined as hypogammaglobulinemia patients.The median survival time was significantly short in MM patients with hypogammaglobulinemia(24 vs 66 months).More importantly,the multivariate and univariate analysis revealed that IgG<5 g/L was an independent prognostic factor for MM patients(P<0.001).3.Flow cytometry results revealed that the proportion of Tfh2/Tfh ratio in the NDMM(Newly diagnosed MM patients)group and the RE(Relapsed MM patients)group were significantly lower than that in the healthy control group(P<0.0001),and the Tfh17/Tfh ratio were significantly increased(P<0.0001).Moreover,the proportion of Tfh17/Tfh ratio was significantly increased compared to the NDMM group(P=0.0077).In addition,the proportion of relapsed MM patients in the IgG<5 g/L group was significantly higher than that of the IgG≥ 5 g/L group(31.25%vs 15.15%).Conclusion1.The diagnosis and treatment of patients with hematological tumors with hypogammaglobulinemia in hematologists,especially IgRT treatment,is still lack.2.IgG<5 g/L was a significant independent prognostic factor for MM patients,which could be a prognostic marker for MM patients.3.The continuous monitoring of IgG<5 g/L and the propotion of Tfh17 cells in Tfh cell could be an indicator to evaluate the immune status of MM patients.