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Objective:To analyze the expression of CD27 on T lymphocytes in the microenvironment of multiple myeloma (MM), and explore whether CD27 level or the CD27-/CD27+ ratio of T-cell affect the prognosis of MM patients.Methods:A total number of 103 newly-diagnosed MM patients from January 2016 to June 2019 were enrolled in the Affiliated Cancer Hospital of Harbin Medical University. All patients received bortezomib-based three-drugs combination regimen. The expression of CD27 on T lymphocytes in bone marrow aspirate samples was detected by flow cytometry before any treatment. MM patients were divided into two groups according to the CD27 level: CD27-high expression group (CD27 expression on T-cells ≥20%) and CD27-low expression group (CD27 expression on T-cells <20%). The clinical characteristics, treatment response and prognosis of patients between the two groups were analyzed using χ 2-test. The survival and clinical information of patients were compared using Kaplan-Meier method, and the related factors related to the survival of MM were analyzed using Cox proportional risk model. Results:Among 103 MM patients, 68 cases (66.0%) were included in CD27 high expression group, and 35 cases (34.0%) were included in low expression group. The percentage of bone marrow plasma cells and β2-MG level in CD27 high expression group were higher than those in CD27 low expression group significantly (54.4% [37/68] vs 22.9% [8/35], χ2=9.352, P=0.002;58.8% [40/68] vs 37.1% [13/35], χ2=4.348, P=0.037), and the proportion of ISS stage Ⅱ-Ⅲ in CD27 high expression group was higher than the counterpart (79.4% [54/68] vs 60% [21/35], χ2=4.399, P=0.036). After 4 cycles of three-drug combination therapy, the overall response rate ( ORR=stringent complete response+complete response+very good partial response+partial response) of the low CD27 expression group was higher than the high expression group (82.9% [29/35] vs 38.2% [26/68], χ2=18.489, P<0.01). The deep response rate to treatment (stringent complete response+complete response+very good partial response) was higher (48.6% [17/35] vs 27.9% [19/68], χ2=4.326, P=0.038), and the progression, free surviva (PFS) was longer (21months vs.14.1months, t=18.655, P<0.001) in the low expression group compared with CD27-high group. Univariate analysis showed that CD27-/CD27+T lymphocyte ratio, ISS stage Ⅱ-Ⅲ, age ≥65 years, β2-Mg ≥3.5 mg/L, and plasma cell proportion ≥30% were associated with the poor prognosis of MM patients, and the differences were significant statistically ( P<0.05). Multivariate analysis showed that CD27-/CD27+T lymphocyte ratio was an independent prognostic factor for 2-year overall survival (OS)( HR=2.425, 95% CI 1.216-4.835, P=0.012) and 2-year PFS ( HR=1.881, 95% CI 1.085-3.260, P=0.024) in MM patients. Conclusions:The expression of CD27 in T lymphocytes is correlated with the prognosis, treatment response and progression-free survival of MM. The ratio of CD27-/CD27+T lymphocytes is an independent prognostic indicator.
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Objective To study the influence of Salviae Miltiorrhizae Radix et Rhizome (SMR) and Carthami Flos (CF) before and after compatibility on activitis of cytochrome P 1A2 (CYP1A2),cytochrome P2E1 (CYP2E1),and cytochrome P3A4 (CYP3A4) from rat liver microsomes.Methods Using caffeine,chlorzoxazone,and midazolam as the probe drugs ofCYP1A2,CYP2E1,and CYP3A4,the SD rats were randomized divided into four groups:control group,SMR (1.2 g crude drug/kg) group,CF (0.4 g crude drug/kg) group,and SMR (1.2 g crude drug/kg) + CF (0.4 g crude drug/kg) group.According to the above dose,rats were ig given drugs for 7 d.Rats were injected with caffeine,chlorzoxazone,and midazolam solution in tail vein 30 rain after the last administration,and the blood was collected at different time points.Metronidazole as internal standard,method has been established to determine the levels of caffeine,chlorzoxazone,and midazolam to evaluate the activities of CYP1A2,CYP2E1,and CYP3A4 by HPLC.Results Compared with control group,SMR increased the clearance rates (CL) of caffeine,chlorzoxazone,and midazolam,reduced the AUC,and t1/2 was also show a decreasing trend,but the difference was not significant.In CF group,CL of caffeine and chlorzoxazone was decreased,but the difference is not significant.CL of midazolam significantly decreased (P ＜ 0.01).AUC of chlorzoxazone increased,but the difference was not significant.AUC of caffeine and midazolam increased significantly (P ＜ 0.05 and 0.01).In SMR + CF group,the CL of caffeine and chlorzoxazone decreased significantly (P ＜ 0.05),the AUC of caffeine and chlorzoxazone increased significantly (P ＜ 0.05),and t1/2 also showed a decreasing trend,but the difference is not significant.Conclusion Compatibility of SMR and CF has an inhibitive effect on CYP1A2 and CYP2E1 in rats,and it could be one of the mechanisms ofinteractive synergy.
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Objective To evaluate immune function of patients with multiple myeloma ( MM) by detect the changes of the Treg cells in bone marrow of patients with MM .Methods Treg cells in peripheral blood and bone marrow of 45 patients with MM and 15 healthy controls were measured by flow cytometry .Results The per-centage of Treg cells in peripheral blood of MM was higher than that in healthy person ;The percentage of Treg cells in MM bone marrow was lower than that in healthy person ,and the extent was positively correlated with the level of β2-MG and ISS(P<0.05).Conclusion MM Patients display an abnormal level of CD 4 +CD25 +Treg cells,which may be an important mechanism of MM immune deficiency .