Correlation Analysis Of T Lymphocyte Subsets And Peripheral Neuropathy In Multiple Myeloma

BackgroudPatients with multiple myeloma（MM）are prone to anemia,thrombocytopenia,infection,fatigue,peripheral neuropathy（PN）and other adverse reactions during chemotherapy,of which PN is one of the most common adverse reactions,mainly manifested by extremities numbness and pain.Its occurrence often leads to drug dosage reduction,treatment delay and even treatment interruption,thus affecting patients’treatment experience and quality of life.However,the exact mechanism of hemotherapy-induced peripheral neuropathy（CIPN）has not been elucidated.Recent studies have proved that immune factors are involved in the pathogenesis of PN,especially CD4⁺T cells and CD8⁺T cells,which are proved to be important influencing factors of PN.ObjectiveThe correlation between the proportion of CD4⁺T cells and CD8⁺T cells in T lymphocyte subsets and PN in newly diagnosed MM patients was explored,which aiming to provide basis for personalized treatment selection of patients.MethodA total of 225 newly diagnosed MM patients admitted to the Department of Hematology,The First Affiliated Hospital of Xinxiang Medical College from October 2018to December 2021 were collected,and 42 patients were finally included in the study through the inclusion criteria.The proportion of CD4⁺T cells and CD8⁺T cells in peripheral blood T lymphocyte subsets was detected by flow cytometry.Clinical data were collected on baseline characteristics,levels of albumin,hypersensitive C-reactive protein,and complement C3 using the hospital’s electronic medical record information system.All patients were diagnosed,treated and followed up in the First Affiliated Hospital of Xinxiang Medical College.SPSS 25.0 was used for statistical analysis.Missing values are filled in using the expected maximization method.Quantitative data were described by mean±standard deviation,and differences between groups were compared by t test.Qualitative data were expressed by absolute and relative numbers,and differences between groups were compared by Fisher’s exact probability method.Median Event Free survival（EFS）was described by Kaplan-Meier method.,and simple associations was analyzed by log-rank test and univariate COX regression.The COX proportional risk model was used for multivariate analysis,The proportional risk hypothesis was tested by Schoenfeld residual of R language,and P<0.05 was considered to be statistically significant.Predictive analysis uses the Receiver Operating characteristic（ROC）curve.Result1.PN occurred in 22（52.4%）of the 42 MM patients,The median EFS of all patients is 92（31,231）days.No potential confounding factors were found in the equilibrium analysis of the proportion of CD4⁺T cells between the two groups.The equilibrium analysis of CD8⁺T cell ratio between the two groups also found no potential confounding factors.2.Log-rank test results showed that there was no significant difference between the high proportion group and the low proportion group of CD4⁺T cells（Log-rank P=0.583）.The difference between the high proportion group and the low proportion group of CD8⁺T cells was statistically significant（log-rank P=0.002）.3.Univariate COX regression analysis showed that:Albumin（HR 0.92,95%CI0.86-0.98,P=0.006）,hypersensitive C-reactive protein（HR 1.02,95%CI1.01-1.03,P=0.011）and the proportion of CD8⁺T cells（HR 0.27,95%CI 0.11-0.65,P=0.004）had statistically significant effect on PN.Gender,age,BMI,proportion of complement C3 and The proportion of CD4⁺T cells had no statistical significance on PN（P>0.05）.4.Multivariate COX regression analysis showed that the proportion of CD8⁺T cells had statistical significance on PN（HR 0.32,95%CI 0.12-0.84,P=0.022）.Albumin,proportion of CD4⁺T cells and hypersensitive C-reactive protein had no statistical significance on PN（P>0.05）.5.Predictive analysis results:According to ROC curve,the optimal critical value of CD8⁺T cell proportion was 18.91%.The sensitivity was 0.55,specificity was 0.95,Yuden index was 0.5,positive predictive value was 92%,negative predictive value was 63%.The area under the curve was 0.752（P=0.005,95%CI 0.604-0.901）.ConclusionLow CD8⁺T cell ratio in T lymphocyte subsets was an independent risk factor for PN in newly diagnosed MM patients.Patients with high CD8⁺T cell ratio had longer EFS and lower PN incidence.The optimal critical value of CD8⁺T cell ratio for PN diagnosis was18.91%,and the accuracy was 75.2%.