| Background and ObjectiveMultiple myeloma(MM)is a highly heterogeneous and aggressive hematologic malignancy with complex clinical manifestations and multiple prognostic factors.With the advancement of research and improvement of treatment protocols,the prognostic assessment of some traditional prognostic factors has gradually decreased,therefore,the clinic has been searching for new prognostic factors.In recent years,it has been found that red blood cell distribution width to platelet ratio(RPR),an inflammatory index,is a prognostic marker for a variety of inflammatory diseases and solid tumors,but it has not been studied in hematologic tumors.In this study,we investigated the correlation between peripheral blood RPR and clinical features such as abnormal plasma cell surface-specific antigen expression and cytogenetic abnormalities in patients with primary MM and analyzed whether there was any association between RPR and prognostic survival time of patients,to investigate the value of peripheral blood RPR values in the prognosis of patients with primary MM.MethodsCollect clinical data of 145 newly diagnosed MM patients at People’s Hospital of Henan University Hospital from May 1,2015 to December 31,2021,including gender,age,hemoglobin,red blood cell distribution width,platelet count,blood calcium,albumin,lactate dehydrogenase,creatinine,immunoglobulin type,β2-microglobulin,bone marrow plasma cell count,D-S(Durie-Salmon stage)staging,ISS(International Staging System)staging,immunophenotype,indirect fluorescence in situ hybridization(FISH)and survival time,etc.The optimal cut-off value of RPR was determined by applying the receiver operating characteristic curve(ROC)and divided into high and low RPR groups;the differences in clinical and laboratory characteristics,immunophenotype and cytogenetic abnormalities,and survival time between the high and low RPR groups were compared;The Kaplan-Meier method was applied to the differences in overall survival(OS)and progression-free survival(PFS)between groups;the factors affecting OS and PFS were screened by Cox univariate regression model,and the multi-factor Cox proportional risk regression model was applied to screen for independent factors of clinical prognosis in newly diagnosed MM patients.Results1.Among 145 patients with primary MM,79(54.5%)were male and 66(45.5%)were female.with a median age of onset of 59(range 38-85 years)years,45(31.0%)patients were aged >65 years,and 100(69.0%)patients were aged ≤65 years.The distribution of cases by type was as follows: According to M-protein typing,there were 64 cases(44.1%)of Ig G type,31 cases(21.4%)of Ig A type,and 50 cases(34.5%)of the light chain and other types;according to Dury-Salmon(DS)staging: 10 cases(6.8%)were stage I,24 cases(16.6%)were stage II,and 111 cases(76.6%)were stage III;pursuant to the international staging system(ISS)staging: 21 cases(14.5%)were stage I,65 cases(44.8%)were stage II,and 59 cases(40.7%)were stage III.Immunophenotypic testing: CD56 positive rate was 61.4%(89/145)and CD117 positive rate was 43.4%(63/145).The cytogenetic analysis referred to interphase fluorescence in situ hybridization(FISH)assay: 1Q21 amplification positive rate was 53.1%(77/145);IGH rearrangement positive rate was 71.7%(104/145);the positive rate of TP53 deletion was 11.7%(17/145).2.Based on the subject working characteristic curve(ROC curve),the optimal cut-off value of RPR was determined to be 0.12,and its area under the curve(AUC)was 0.769,with a sensitivity of 68.3% and specificity of 77.6%,divided into high RPR group(RPR ≥ 0.12)and low RPR group(RPR < 0.12);There were 61(42.1%)and 84(57.9%)patients in the high RPR and low RPR groups,respectively.3.By analyzing the data of patients with newly diagnosed MM before the first treatment.To compare whether there was any difference between groups in terms of clinical characteristics such as gender and age between patients in the high RPR group and low RPR group.The differences between the two groups were analyzed by χ2 test,and the results showed that MM patients in the high RPR group were more likely to have anemia,thrombocytopenia,hyper-β2 macroglobulinemia,increased percentage of bone marrow plasma cells,a high percentage of DS stage III,and a high percentage of ISS stage III compared with patients in the low RPR group(P < 0.05),while the two groups were more likely to have anemia,age,M protein typing,albumin,creatinine,lactate dehydrogenase,and serum calcium were not statistically significant(P > 0.05).4,Analysis of MM cytogenetics in the high RPR and low RPR groups showed that the proportion of1Q21 amplification(65.6% vs.44.0%,P=0.010)and IGH positivity(80.3% vs.65.6%,P=0.050)were significantly higher in the high RPR group than in the low RPR group,while the difference in the proportion of abnormal TP53 expression between the two groups was not statistically significant(P>0.05).5.Analysis of the immunophenotypic characteristics of MM cells in the high RPR and low RPR groups showed that the percentage of positive CD56 expression was significantly higher in the low RPR group(72.6% vs.45.9%,P=0.001)than in the high RPR group,while the difference in the percentage of positive CD117 expression between the two groups was not statistically significant(P>0.05).6.Survival analysis showed that the median OS time was 24 months and not reached in the high RPR and low RPR groups,respectively,and the difference was statistically significant(P<0.001);the median PFS time was 11 months and 28 months in the high RPR and low RPR groups,respectively,and the difference was statistically significant(P<0.001);Further analysis of whether immunophenotype and cytogenetics had any effect on the poor prognosis of RPR suggested that the effect of RPR on survival was independent of immunophenotypic and cytogenetic abnormalities.Multifactorial Cox regression analysis showed that high RPR was an independent risk factor for OS and PFS in MM patients.Survival analysis was performed in different subgroups,Patients were divided into two groups according to age,and in MM patients aged≤ 65 years,high RPR was associated with shorter median OS time(24 months vs.not achieved,P<0.001)and median PFS time(13 months vs.29 months,P<0.001);In patients aged >65 years,median OS time was 24 months in the high RPR and low RPR groups,respectively and 37 months(P=0.011),and median PFS time was 8 and 20 months(P=0.033),respectively,with statistically significant differences.Conclusion1、High RPR was closely associated with adverse clinical parameters(late staging,high bone marrow plasma cell ratio,high β2-MG level and anemia,low platelet count,etc.);high RPR was more prone to1Q21 amplification and IGH translocation;immunophenotypic characterization showed that CD56 positive expression rate was lower in high RPR than in low RPR group.2、Multivariate Cox regression analysis showed that high RPR was an independent risk factor for OS and PFS in MM patients.The role of RPR level on the prognosis of MM patients was not affected by specific immunophenotypic expression,and karyotype abnormalities,and could exist as a group of a relatively high-risk population.RPR as a simple and effective indicator can assist in assessing the prognosis of MM patients and can be used as a predictor of newly diagnosed MM patients as a complementary indicator to predict prognostic survival.3、In MM patients aged ≤65 years and aged >65 years,the median OS time and median PFS time were significantly shorter in the high RPR group than in the low RPR group,and RPR can be a useful supplement to MM risk stratification and contribute to further accurate stratification. |
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