| Objective:To explore the relationship between the proportion of abnormal plasma cells in patients with multiple myeloma(MM)and the decline index after treatment with clinical features and prognosis,and to explore the relationship between abnormal circulating plasma cells and prognosis.Method:1.Retrospective analysis of the clinical data of 123 MM patients with complete follow-up data in our hospital from January 2017 to November 2019.The diagnosis and staging standards of the patients were in accordance with the standards of the International Myeloma Working Group(IMWG).Received induction therapy based on PD(bortezomib+dexamethasone)for 4-6 courses;after the second and fourth courses,bone marrow cell morphology assessment and bone marrow flow cytometry were performed,and analyzed The relationship between abnormal plasma cell decline index and prognosis after the second course of induction therapy and the fourth course of treatment.Abnormal plasma cell decline index=(number of abnormal plasma cells initially diagnosed-number of abnormal plasma cells after treatment)/number of abnormal plasma cells initially diagnosed;Decline index=1 means that no plasma cells can be detected in smear or flow cytometry,which is equivalent to MRD negative.Immature plasma cell-dominated type:The ratio of immature plasma cells in bone marrow slices to more than 50%of all plasma cells is defined as immature plasma cell-dominated type.2.From November 2019 to December 2020,15 MM patients were admitted to our hospital for the first time and received their informed consent.When the patient was first diagnosed and undergoing bone marrow aspiration to evaluate the treatment effect,peripheral blood was drawn at the same time,and the10-color flow cytometry technique was used to detect the circulating plasma cells in the peripheral blood.The laboratory positive standard is defined as≥50 abnormal plasma cells in 500,000 nucleated cells in peripheral blood,with a sensitivity of 10-4.Analyze the relationship between the index of circulatory abnormal plasma cell decline and the prognosis after the end of the second and the fourth time of induction therapy.Result:1.General clinical data:The median age of 123 patients was 60 years(35,88),of which 70 were males,accounting for 56.9%;the median of various indicators at onset:hemoglobin 82(39,139)g/L;platelet count 171(8,463)×10~9/L;albumin 32.6(17.2,45.1)g/L;β2 microglobulin(β2-MG)5.6(1.43,19.65)g/L;lactate dehydrogenase(LDH)178(67,3351)umol/L;creatinine 90(39,1304)umol/L;blood calcium 2.32(1.69,3.49)mmol/L;total number of plasma cells in bone marrow smear 33.6%(5.2%,95.6%);abnormal plasma cells detected by flow immunophenotyping The number is 10.70%(0.63%,66.48%).After the second course of treatment,bone marrow smear plasma cell decline index=1 in 1 case.After the second course of treatment,the bone marrow flow plasma cell decline index was not equal to 1.After the fourth course of treatment,the bone marrow smear plasma cell decline index,bone marrow Flow cytometry plasma cell decline index=1 63cases and 53 cases,respectively.After the second course of treatment,the median of bone marrow smear plasma cell and bone marrow flow plasma cell decline index were 0.75(0.15,1.00)and 0.78(0.06).,0.98);after the 4th course of treatment,the median values of plasma cell and bone marrow flow plasma cell decline index were 0.97(0.10,1.00)and 0.99(0.17,4.12),respectively.2.The relationship between bone marrow plasma cell decline index and patient clinical data:After the second course of treatment,the bone marrow flow plasma cell decline index was not equal to1,and there was no difference.After the 4th course of treatment,70 cases(56.9%)of the bone marrow flow plasma cell decline index were not equal to 1,compare the two groups of patients(the bone marrow flow plasma cell decline index equal to 1 and not equal to 1 after the 4th course of treatment)The clinical characteristics of the two groups of patients were not significantly different in gender,age,albumin,platelet count,β2 microglobulin,LDH,blood calcium,the number of newly diagnosed bone marrow plasma cells,DS staging and ISS staging,among which the maturation status of newly diagnosed plasma cells There was a significant difference between the two groups.Patients with bone marrow plasma cells dominated by immature plasma cells did not easily turn negative after the fourth course of treatment(P value<0.05).3.Analysis of relevant prognostic factors:Single factor analysis:Age,β2 microglobulin,blood calcium,whether there is kidney damage,the maturation status of plasma cells at the first diagnosis,the bone marrow flow plasma cell decline index after the fourth course of treatment,and after the fourth course of treatment have a significant impact on PFS Bone marrow smear plasma cell decline index(P values are 0.023,0.024,0.01,0.039,<0.01,<0.01,and 0.01);the ones that have a significant impact on OS are age,platelet count,β2 microglobulin,lactate dehydrogenase,Blood calcium,whether there is kidney injury,newly diagnosed plasma cell maturation status,ISS staging,bone marrow flow plasma cell decline index after the fourth course of treatment,bone marrow smear plasma cell decline index after the fourth course of treatment(P value is 0.012,respectively)0.015,0.009,0.04,<0.01,0.014,<0.01,0.024,<0.01 and<0.01).Multivariate analysis:Platelet count<100×10~9/L,blood calcium≥2.65mmol/L,maturation status of plasma cells at first diagnosis(major plasma cell type),and bone marrow flow plasma cell decline index(≠1)after the fourth course of treatment affect the patient Independent risk factors for PFS(P values were0.034,0.019,<0.01,<0.01);platelet count<100×10~9/L,maturation status of newly diagnosed plasma cells(major plasma cell type),bone marrow after the fourth course of treatment The flow cytometry plasma cell decline index(≠1)is an independent risk factor that affects the patient’s OS(P values are 0.013,<0.01,<0.01,respectively).4.Survival comparison:The PFS and OS of patients with bone marrow plasma cells dominated by mature plasma cells at the first diagnosis were significantly better than those with immature plasma cells at the first diagnosis.The median PFS and OS were(29.3 months VS 10.8 cases).Months)and(36.1 months vs 15.1 months),P<0.05;PFS and OS of patients with bone marrow flow plasma cell decline index equal to 1 after the 4th course of treatment were significantly better than those of the 4th course of treatment In patients with cell decline index≠1,the median PFS and OS were(29.6 months VS 15.2 months)and(32.7 months VS 18.9months),P<0.05.ROC curve was used to show that the flow cytometric detection of abnormal bone marrow plasma cells≥5.75%was selected as the best positive diagnostic threshold for OS prognosis(sensitivity 76.9%,specificity 53.3%,area under the curve:0.644,P=0.008),abnormal flow cytometry plasma The OS of patients with cell<5.75%was significantly better than that of patients with abnormal bone marrow flow cytometry≥5.75%.The median OS was 39.0 months vs.19.9 months,p<0.05;ROC curve showed abnormal morphology of bone marrow cells≥2.5%Was selected as the best positive diagnostic threshold for OS prognosis(sensitivity 80.8%,specificity 48.9%,area under the curve:0.670,P=0.002).The OS of patients with abnormal bone marrow morphology less than 2.5%of protomyelocytic cells was significantly better than that of patients with abnormal bone marrow morphology≥2.5%.The median OS was 38.4 months vs.19.6 months,P<0.05.5.Correlation analysis between abnormal plasma cell decline index and prognosis:After the second course of treatment,the bone marrow smear plasma cell decline index and the bone marrow flow plasma cell decline index after the second course of treatment have no significant correlation with PFS and OS,P>0.05;the bone marrow smear plasma cell decline index after the fourth course And after the 4th course of treatment,the bone marrow flow plasma cell decline index has a non-linear correlation with PFS and OS,P<0.05,negative MRD in the 4th course of treatment indicates a better prognosis.6.Circulating plasma cells in peripheral blood:Ten-color flow cytometry was used to detect circulating plasma cells in peripheral blood.Because of the small sample size,statistical analysis was not possible.Analysis of clinical features found that there were 4 cases(26.7%)in the positive group of peripheral blood circulating plasma cells,and plasma cells were seen in the morphological analysis of peripheral blood.In 2 patients(13.3%),peripheral blood flow testing was more sensitive than peripheral blood morphological observation counts,and could better predict the prognosis;patients in the peripheral blood circulating plasma cell positive group were not easy to complete remission after 4 courses;patients with hemoglobin,platelet counts,Indexes such as albumin and plasma cell decline index after the second and fourth courses of treatment were lower in the peripheral blood circulating plasma cell-positive group than in the peripheral blood circulating plasma cell-negative group;creatinine,blood calcium,LDH,β2-MG,bone destruction,and newly diagnosed bone marrow The number of morphological plasma cells,the number of plasma cells detected by flow cytometry and other indicators were higher in the peripheral blood circulating plasma cell positive group than the peripheral blood circulating plasma cell negative group.Conclusions:1.The prognosis of MM patients with newly diagnosed bone marrow immature plasma cells is poor,and the prognosis of patients with newly diagnosed bone marrow abnormal protoplasmocytes≥2.5%and newly diagnosed bone marrow abnormal plasma cells≥5.75%is poor;2.In the era of new drugs,platelet count<100×10~9/L,maturation state of plasma cells at the first diagnosis(major plasma cell type),and bone marrow flow plasma cell decline index(≠1)after the fourth course of treatment affect the OS of MM patients Independent risk factors;3.The prognosis of patients with abnormal circulating plasma cells in peripheral blood is poor.Flow cytometric detection of peripheral plasma cells is more meaningful than morphological analysis of peripheral blood.Positive circulating plasma cells in peripheral blood can be used as an indicator of poor prognosis for patients. |
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