Diagnosis and treatment of multiple myeloma in Hunan Province / 中南大学学报(医学版)

OBJECTIVES@#There is less clinical data on multiple myeloma (MM) in China, and the aim of this study was to collect and analyze the clinical data of newly diagnosed multiple myeloma (NDMM) patients in Hunan Province during 1 year, to understand the real clinical features and treatment outcome for Hunan Province patients with MM, and to strengthen the understanding of the standardized diagnosis process and treatment plan of MM.@*METHODS@#The clinical data of 529 patients with NDMM in 12 large-scale general hospitals in Hunan Province from January 1 to December 31, 2019 were collected and analyzed, including baseline data, treatment regimens, duration of treatment, and adverse reactions. The clinical characteristics, treatment, and safety of patients were analyzed by SPSS 21.0.@*RESULTS@#Among the 529 NDMM patients, the age was 33-90 (median 64) years and the male-female ratio was 1.38꞉1. The clinical features ranged from high to low were as follows: Bone pain (77.7%), anemia (66.8%), renal insufficiency (40.6%), hypercalcemia (15.1%). Typing: IgG 46.5%, IgA 24.6%, IgD 2.6%, IgM 0.8%, light chain 15.7%, double clone 3.0%, no secretion 0.6%, absence 6.2%. Staging: Durie-Salmon stage I, II, and III were 4.5%, 10.6%, 77.3%, respectively, and 40 cases (7.6%) missed this data. International Staging System (ISS) stage I, II, and III were 10.4%, 24.4%, and 47.6%, respectively, and 93 cases (17.6%) were missing. Revised International Staging System (R-ISS) stage I, II, and III were 5.5%, 27.0%, 23.1%, respectively, and 235 cases (44.4%) missed this data. Among the 98 NDMM patients in the Third Xiangya Hospital, Central South University, Durie-Salmon (DS) stage missing 2.0%, ISS stage missing 12.3%, and R-ISS stage missing 12.3%.Treatment: Among the 529 patients,475 received treatment, the rate of treatment was 89.8%; 67.4% of the patients were able to complete four courses of chemotherapy at induction phase, 90.3% of the patients received proteasome inhibitor based combination chemotherapy regimen more than once, 67.2% received immunomodulator based regimen more than once, and 59.8% of the patients received proteasome inhibitor and immunomodulator based combination chemotherapy regimen more than once. Curative: Overall response rate (ORR) and high quality response rate (HQR) of the 4-course group were better than those of the 2-course group (ORR: 85% vs 65%, P=0.006; HQR: 68.3% vs 24.0%, P<0.001). The HQR of the standard chemotherapy group was better than that of the non-standard chemotherapy group (65.1% vs 48.2%, P=0.035). Adverse reactions during treatment included hematologic toxicity (17.5%), peripheral neuropathy (24.8%), gastrointestinal adverse events (23.8%), pulmonary infection (25.9%), herpes zoster (4.6%), and venous thrombotic events (1.7%).@*CONCLUSIONS@#In 2019, the missed diagnosis rate of MM patients was high, the medium age of diagnosis was older, and the accuracy of patient diagnosis was not high. There is a great difference among medical centers, especially in the stage and risk stratified, nearly half of NDMM patients are not diagnosed with R-ISS stage; the lack of cytogenetic data needs to be supplemented by follow-up studies. A high proportion of patients with NDMM present with bone pain and anemia.Patients received treatment have higher use of chemotherapy regimens containing proteasome inhibitors and/or immunomodulators, but there is a significant gap among different medical centers, and standardized treatment needs to be strengthened. The safety during chemotherapy is controllable.

To investigate the relationship between P15INK4B gene promoter methylation degree and different types of MDS and prognosis / 中国医师杂志

Objective To determine the methylation level of P15INK4B gene promoter in different types of myelodysplastic syndromes (MDS) and its correlation with its prognosis.Methods Methylation frequency of the P15INK4B gene promoter in 44 cases of MDS were determined by methylation-specific polymerase chain reaction (PCR) and pyrosequencing,and its correlation with clinical classification and characteristics of MDS were statistically analyzed.Results Frequency of P15INK4B gene promoter methylation in myelodysplastic syndromes-refractory anemia with excess blasts Ⅱ (MDS-RAEB Ⅱ) patients was (46.89 ± 15.41) ％,significandy higher than that in other types of MDS (P ＜ 0.05),but no difference in promoter methylation frequency was detected among the other types of MDS (P ＞ 0.05) ; frequency of P15INK4B gene promoter methylation was found to be correlated with decline in platelet upon diagnosis (t =9.02,P ＜ 0.01),but showed no significant correlation with drop of hemoglobin or leukopenia (P ＞0.05).As for the correlation between P15INK4B gene promoter methylation and MDS risk stratification,no significant difference was detected between the low-risk and very low-risk groups (P ＞ 0.05),but significant differences were detected among the medium-risk,high-risk,and very high-risk groups (P ＜ 0.05).In addition,frequency of P15INK4B gene promoter methylation was (49.21 ± 8.78)％ in MDS patients that developed leukemia in the following two year,significantly higher than that in MDS patients who didn't (19.64 ± 6.24) ％ (P ＜ 0.05).Conclusions P15INK4B gene promoter methylation frequency is a valuable indicator of prognosis of MDS patients.

The clinic study of JAK2V617F mutation detection in diagnosis of polycythemia vera / 中国医师杂志

Objective To investigate the diagnostic value of JAK2V617F mutation detection in the diagnosis of polycythemia vera,and screen a more simple method for clinic laboratory to detect the mutation of JAK2V617F.Method DNA was extracted by standard procedures after isolating total leukocytes from peripheral blood mononuclear cells by density gradient centrifugation over Histopaque 1077.DNA samples were amplified,and single-stranded biotinylated PCR products were prepared for sequencing.At the same time,in order to testify the reliability of the allele-specific PCR,two forward primer and one common reverse primers were applied for identifying the mutation.Result In 32 of 38 patients with polycythemia vera,JAK2V617F mutation was determined by conventional DNA sequencing.35 JAK2V617F mutations were detected by the allele-specific PCR.and these mutations were confirmed by DNA sequencing.None mutation was found in secondary polycythemia and normal control.Conclusion JAK2V617F function mutation occuis in nearly all patients with PV,and JAK2V617F mutation should be a molecular marker in the diagnosis of polycythemia vera.Allele-specific PCR is a very sensitive and specific method for detecting JAK2V617F mutation.