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Objective:To investigate the therapeutic effect and safety of pomadomide combined with cyclophosphamide and dexamethasone (PCD) in the treatment of relapsed/refractory multiple myeloma (MM).Methods:The clinical data of 20 relapsed/refractory MM patients receiving PCD regimen in the Second People's Hospital of Lianyungang Affiliated to Bengbu Medical College from March 2021 to June 2022 were retrospectively analyzed; and 29 relapsed/refractory MM patients receiving other regimens including DECP (dexamethasone+etoposide+cyclophosphamide+cisplatin, 13 cases) and VCD (bortezomib+ cyclophosphamide+ dexamethasone, 16 cases) during the same period were treated as the control group. The efficacy and adverse effects of both groups were compared after 4 cycles of treatment.Results:After 4 cycles of treatment, the overall response rate (ORR) and the clinical benefit rate (CBR) of 20 cases in PCD group was 70.0% (14/20) and 85.0% (17/20), respectively; among 20 cases, there were 5 cases of complete response (CR), 4 cases of very good partial remission (VGPR), 5 cases of partial remission (PR), 3 cases of minimal remission (MR), 2 cases of stable disease (SD), 1 case of the progression of the disease (PD). ORR and CBR of 29 cases in the control group was 41.4% (12/29) and 65.5% (19/29), respectively; among 29 cases, there were 2 cases of CR, 3 cases of VGPR, 7 cases of PR, 7 cases of MR, 5 cases of SD, 5 cases of PD. There was a statistically significant difference in ORR of both group ( χ2 = 3.89, P = 0.048), while the difference in CBR of both group was not statistically significant ( χ2 = 2.30, P = 0.129). There were 2 patients with renal impairment achieving CR in PCD group and 1 patient with renal impairment achieving CR in the control group ( P = 0.152); 1 genetically high-risk patient achieved CR in PCD group and none of patients in the control group achieved CR, and the difference was statistically significant ( P>0.05). The common hematological adverse effects of two groups were anemia, neutropenia, thrombocytopenia; the common non-hematological adverse effects were malaise, infection and fatigue, and the differences were statistically significant (all P>0.05). The incidence of grade 3-4 infection was 25.0% (5/20) in PCD group and the disease was under the control after anti-infective therapy, and the incidence of grade 3-4 infection was 24.1% (7/29) in the control group; and the difference was not statistically significant ( P > 0.05). Conclusions:PCD regimen has good clinical efficacy and safety in treatment of relapsed/refractory MM.
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Bendamustine, a bifunctional derivate of nitrogen mustard, is an attractive treatment option for multiple myeloma (MM) due to its specific mode of activity, favorable toxicity profile, and clinical activity in patients resistant to alkylating agent. Bendamustine single agent and its combination with immunomodulators or proteasome inhibitors have been widely used in the relapsed/refractory MM patients. Bendamustine has brought the longer progression-free survival, overall survival time and deeper remission in the autologous stem cell transplantation pre-conditioning for MM patients. This paper reviews the treatment progress of bendamustine for MM.
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Objective:To investigate the changes of related indicators of right heart hypofunction in patients with primary myelofibrosis (PMF).Methods:The clinical data of 55 PMF patients in the Second People's Hospital of Lianyungang in Jiangsu Province and Jiangsu Province Hospital from January 2015 to August 2019 were retrospectively analyzed. The differences in right heart function-related echocardiographic indexes and biochemical indexes between pre-fibrosis/early stage fibrosis patients and obvious stage fibrosis patients were compared. Single factor linear regression method was used to analyze the correlations of pulmonary artery pressure with biochemical indexes.Results:The hemoglobin level [119 g/L (47-224 g/L) vs. 78 g/L (33-182 g/L)] and platelet count [233×10 12/L (5×10 12/L-984×10 12/L) vs. 117×10 12/L (7×10 12/L-731×10 12/L)] of patients in the pre-fibrosis/early stage fibrosis group were higher than those in the obvious stage fibrosis group, and the differences were statistically significant (both P<0.05). Among 22 patients with complete results of cardiac ultrasound, 90.9% (20/22) patients had increased pulmonary artery pressure, 72.7% (16/22) patients had increased left atrial diameter, and 90.9% (20/22) patients had increased right ventricular diastolic diameter. There were no patients with abnormal ejection fraction. The pulmonary artery pressure [48 mmHg (46-90 mmHg) vs. 33 mmHg (20-50 mmHg) (1 mmHg = 0.133 kPa)], left ventricular diastolic diameter [46 mm (36-50 mm) vs. 47 mm (43-53 mm)] and fractional shortening rate [38.1% (36.0%-38.9%) vs. 35.4% (32.7%-37.8%)] of patients in the pre-fibrosis/early stage fibrosis group were higher than those in the obvious stage fibrosis group, and the differences were statistically significant (all P < 0.05). The pulmonary artery pressure of patients had positive correlations with age ( r = 0.590), serum ferritin (SF) ( r = 0.608), lactate dehydrogenase (LDH) ( r = 0.711) and soluble growth-stimulating expression gene 2 (ST-2) ( r = 0.580)(all P<0.05), and had negative correlation with platelet count ( r = -0.596, P = 0.003). Conclusion:PMF patients are prone to right heart hypofunction, the pulmonary artery pressure is higher in older patients and patients with high SF, LDH and ST-2 levels and low platelet count.
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Objective@#To investigate the expressions of tissue factor (TF) and vascular endothelial growth factor (VEGF) in diffuse large B-cell lymphoma (DLBCL) and their clinical significances.@*Methods@#The clinical data of 80 cases of DLBCL diagnosed at the Second People's Hospital of Lianyungang from January 2010 to December 2017 were collected, and 30 cases of reactive hyperplasia of lymph node (RLN) were selected as the controls. The expressions of TF and VEGF in the two groups were detected by using immunohistochemical staining.@*Results@#The positive rate of TF and VEGF in the DLBCL group was higher than that in the RLN group [TF: 86.3% (69/80) vs. 50.0% (15/30) ; VEGF: 90.0% (72/80) vs. 53.3% (16/30) ; both P < 0.01]. And there was a positive correlation between the expression of TF and VEGF (r = 0.704, P < 0.05). There was no significant difference in the positive rates of TF and VEGF among the patients with different gender, age and Hans subtypes in DLBCL group (all P > 0.05). The positive rate of TF in DLBCL patients with B symptom, increased LDH, physical status grade ≥2, and extranodal lesion number >1 was higher (all P < 0.05). The positive rate of VEGF in patients with Ann Arbor stage Ⅲ-Ⅳ, B symptom, increased LDH, and extranodal lesion number >1 was higher (all P < 0.05). The positive rate of TF in international prognostic index (IPI) high-risk group was higher than that in low-risk group (P < 0.01); the positive rate of VEGF in IPI high-risk group and middle-high-risk group was higher than that in low-risk group (all P < 0.01). The expressions of TF (r = 0.491, P < 0.01) and VEGF (r = 0.529, P < 0.01) were positively correlated with IPI. The overall survival rates of TF and VEGF low-expression group were higher than those of TF and VEGF high-expression group (both P < 0.05).@*Conclusion@#The expressions of TF and VEGF are highly expressed in DLBCL, which is associated with the IPI. It can provide a reference value in evaluating prognosis of DLBCL.
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Objective:To investigate the effect of CUEDC1 gene on the acute monocytic leukemia THP-1 cells gene expression profile.Methods:The differential expression gene bank of THP-1 cells with CUEDC1 gene interference was constructed. The differential gene expression of THP-1 cells in CUEDC1 interference group and the negative control group was compared based on RNA sequencing technology. The part of the differentially expressed genes were verified by using real-time polymerase chain reaction (PCR), and the up-regulated and down-regulated genes were respectively imported into DAVID software for gene ontology (GO) function enrichment analysis.Results:The differentially expressed gene bank of THP-1 cells interfered by CUEDC1 gene was successfully constructed. A total of 161 differentially expressed genes were detected in CUEDC1 interference group and the negative control group ( P < 0.05), including 85 up-regulated genes and 76 down-regulated genes. There were 9 genes related to cell proliferation and 10 genes related to apoptosis, 2 genes related to p53 gene and 3 genes related to transcriptional regulation, 8 genes related to ubiquitin, among which SMAD5, SG15, CBLL1, FANCF and other genes were closely related to the occurrence and development of acute leukemia. Conclusion:CUEDC1 gene participates in the occurrence and development of acute monocytic leukemia by influencing the expressions of SMAD5, SG15, CBLL1, FANCF and other genes.
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Objective:To improve the cognition of T-cell large granular lymphocytic leukemia (T-LGLL) combined with pure red cell aplasia (PRCA).Methods:The clinical characteristics, peripheral blood and bone marrow laboratory indicators of 14 newly diagnosed patients with T-LGLL combined with PRCA who were admitted to the Second People's Hospital of Lianyungang Affiliated to Bengbu Medical College and the People's Hospital of Jiangsu Province from August 2010 to October 2019 were retrospectively analyzed.Results:Among the 14 patients, there were 7 males and 7 females, with a median age of 58.5 years (33-75 years). At the first visit, the median white blood cell count was 5.02×10 9/L [(1.45-8.49)×10 9/L], the median absolute value of neutrophils was 1.35×10 9/L [(0.43-7.16)×10 9/L], the median lymphocyte ratio was 0.49 (0.13-0.77), the median hemoglobin was 58 g/L (42-106 g/L), the median red blood cell count was 2.01×10 12/L [(0.99-3.20)×10 12/L], the median reticulocyte count percentage was 0.52 (0.14-3.02), the median platelet was 96×10 9/L [(38-281)×10 9/L], the median large granular lymphocytes accounted for 71% (32%-81%) of lymphocytes. Bone marrow aspiration showed that the median large granular lymphocytes accounted for 0.16 (0.08-0.41) of nuclear cells, and the median serum β 2 microglobulin was 4.85 mg/L (2.81-7.22 mg/L). Two patients had ASXL1 and TET2 mutations, and one of them had STAT3, EP300 and FAM46C mutations. Six patients were T cell receptor (TCR) β and γ-positive, 1 patient were TCRβ-positive, 4 patients were TCRγ-positive, 1 patient was TCRδ-positive, 1 patient was TCRβ, γ and δ-positive, and 1 patient was all negative. Eight cases received cyclosporine therapy, 6 cases were effective; 6 cases received methotrexate combined with hormone therapy, 3 cases were effective. The initial induction therapy was effective in 9 cases, 5 patients who failed in the initial treatment received salvage treatment, and 2 cases were effective. Conclusions:The laboratory characteristics of patients with T-LGLL combined with PRCA are similar to those of simple T-LGLL, anemia is a prominent manifestation accompanied by neutropenia or thrombocytopenia. The large granular lymphocytes are easily seen in peripheral blood and bone marrow, and T monoclonal rearrangement of lymphocytes is an important feature, and the patients respond well to immunosuppressive therapy.
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Objective:To investigate the expressions of tissue factor (TF) and vascular endothelial growth factor (VEGF) in diffuse large B-cell lymphoma (DLBCL) and their clinical significances.Methods:The clinical data of 80 cases of DLBCL diagnosed at the Second People's Hospital of Lianyungang from January 2010 to December 2017 were collected, and 30 cases of reactive hyperplasia of lymph node (RLN) were selected as the controls. The expressions of TF and VEGF in the two groups were detected by using immunohistochemical staining.Results:The positive rate of TF and VEGF in the DLBCL group was higher than that in the RLN group [TF: 86.3% (69/80) vs. 50.0% (15/30) ; VEGF: 90.0% (72/80) vs. 53.3% (16/30) ; both P < 0.01]. And there was a positive correlation between the expression of TF and VEGF ( r = 0.704, P < 0.05). There was no significant difference in the positive rates of TF and VEGF among the patients with different gender, age and Hans subtypes in DLBCL group (all P > 0.05). The positive rate of TF in DLBCL patients with B symptom, increased LDH, physical status grade ≥2, and extranodal lesion number >1 was higher (all P < 0.05). The positive rate of VEGF in patients with Ann Arbor stage Ⅲ-Ⅳ, B symptom, increased LDH, and extranodal lesion number >1 was higher (all P < 0.05). The positive rate of TF in international prognostic index (IPI) high-risk group was higher than that in low-risk group ( P < 0.01); the positive rate of VEGF in IPI high-risk group and middle-high-risk group was higher than that in low-risk group (all P < 0.01). The expressions of TF ( r = 0.491, P < 0.01) and VEGF ( r = 0.529, P < 0.01) were positively correlated with IPI. The overall survival rates of TF and VEGF low-expression group were higher than those of TF and VEGF high-expression group (both P < 0.05). Conclusion:The expressions of TF and VEGF are highly expressed in DLBCL, which is associated with the IPI. It can provide a reference value in evaluating prognosis of DLBCL.
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Coupling of ubiquitin conjugation to estrogen receptor degradation (CUE) domain containing protein, a newly discovered ubiquitin binding protein that contains CUE domain, plays an important role in the tumor formation, metastasis and drug resistance. Some researches have showed that CUE domain-containing protein 1 (CUEDC1) is associated with tumor lymphatic metastasis, and CUE domain-containing protein 2 (CUEDC2) is involved in the occurrence and development of solid tumors and leukemia by regulating cell cycle and signaling pathway activity. This review summarizes the CUE domain containing protein structure and the functions in the occurrence, progression, metastasis and drug-resistance of solid tumors and leukemia.
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Coupling of ubiquitin conjugation to estrogen receptor degradation (CUE) domain containing protein, a newly discovered ubiquitin binding protein that contains CUE domain, plays an important role in the tumor formation, metastasis and drug resistance. Some researches have showed that CUE domain-containing protein 1 (CUEDC1) is associated with tumor lymphatic metastasis, and CUE domain-containing protein 2 (CUEDC2) is involved in the occurrence and development of solid tumors and leukemia by regulating cell cycle and signaling pathway activity. This review summarizes the CUE domain containing protein structure and the functions in the occurrence, progression, metastasis and drug-resistance of solid tumors and leukemia.
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Objective To analyze some related causes of hypocytosis or hematocytosis with bone marrow dry pumping. Methods Bone marrow histology, reticular fiber staining and selective immunohistochemical staining were performed in 34 bone marrow dry pumping patients with hypocytosis or hematocytosis in the Second People's Hospital of Lianyungang from January 2012 to August 2017. Results All the patients showed dizziness, fatigue, splenomegaly, night sweats and bleeding, including primary myelofibrosis (17 cases, 50.0 %), chronic myelocytic leukemia (4 cases, 11.8 %), acute myelocytic leukemia (2 cases, 5.9 %), acute lymphoblastic leukemia (1 case, 2.9 %), myelodysplastic syndrome (2 cases, 5.9 %), multiple myeloma (2 cases, 5.9 %), non-Hodgkin lymphoma with bone marrow infiltration (2 cases, 5.9 %), polycythemia vera (1 case, 2.9 %) and bone marrow metastatic tumor (3 cases, 8.8 %). The bone marrow proliferative degree in primary myelofibrosis group was mainly "grade Ⅱ" to "grade Ⅳ", and the non primary myelofibrosis group was mainly "grade Ⅲ" to "grade Ⅴ", and the differences of proliferative degree component between them were statically significant (χ2＝ 12.900, P＝ 0.004). The fibrosis level in primary myelofibrosis group was mainly "grade 2" to "grade 3", and the non primary myelofibrosis group was mainly "grade 1" to "grade 2", and the differences of myelofibrosis degree component between them were also statistically significant (χ2＝ 12.692, P＝ 0.003). Conclusions Hematological malignancies, especially primary myelofibrosis, are the common causes of bone marrow "dry pumping". Bone marrow histology, reticular fiber staining and selective immunohistochemical staining are of great significance in the etiological diagnosis.
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Objective To investigate the clinical and laboratory features of IgG-2κ light chain multiple myeloma. Methods The clinical data and laboratory results of 2 multiple myeloma (MM) patients with IgG-2κ light chain were analyzed and the related literatures were reviewed. Results Two male and 1 female patients were 50-82 years old and mainly suffered with backache, infection, anemia and renal dysfunction. Multiple osteolytic bone destruction was detected in X-ray as well as magnetic resonance imaging (MRI). The level of serum IgG was normal, slight or obviously increased, but the levels of IgA and IgM were decreased. The levels of κ light chain in serum and urine were both increased significantly, and Bence-Jones protein was positive. Double M protein peaks of serum in γ area were detected by protein electrophoresis in 2 patients. A single band of IgG and double bands of light chain κ were revealed by immunofixation electrophoresis. Bone marrow smear showed that abnormal plasma cells were increased obviously. One patient gave up chemotherapy because of lung infection, acute left heart failure and acute renal failure, the others 2 patients achieved partial remission and stable disease by receiving DVD and VAD chemotherapy. Conclusions IgG-2κ light chain MM lacks typical clinical presentation, but some laboratory characteristics may be different from those of IgG-κ light chain. Further researches are needed to confirm whether or not it belongs to biclonal MM.
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Objective To explore the efficacy and adverse reactions of improved VTD regimen (pirarubicin combined with vincristine and dexamethasone) plus low-dose thalidomide in patients of newly diagnosed multiple myeloma(MM).Methods Twenty-nine cases of newly diagnosed MM were enrolled in this study.The improved VTD regimen was intravenous injection vincristine 2 mg/d on the first day,intravenous drip pirarubicin 20-30 mg/d from the first day to the second day,and intravenous drip dexamethasone 8 mg/d from the first day to the tenth day.Twenty-eight days was one course of treatment.Response and adverse reactions were evaluated after 4 course of treatment.On the first day of chemotherapy,all the patients were orally administered thalidomide 50 mg/d.Three days later,thalidomide was added to 100 mg/d and chronically maintained if toxicities could be tolerated.Results There were 3 cases(10.3％) in complete response,12 cases (41.2％) in very good partial response,10 cases (34.5％) in partial response,3 cases (10.3％) in stable disease,and 1 case(3.5％) in progressive disease.The overall response rate was 86.2％.Main adverse reactions were myelosuppression,asthenia and constipation,all could be tolerated.Conclusion It has significant response rate and less side effects of improved VTD regimen plus low-dose thalidomide for the patients of newly diagnosed multiple myeloma,and deserves further clinical practice.
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Lamivudine [LAM] is commonly used to treat Hepatitis B virus [HBV] infection, but its use frequently induces drug resistance. Therefore, rapid and correct detection of drug-resistant HBV is important for effective treatment of HBV infection. In this study, we aimed to develop a novel, simple, and user-friendly method for the detection of LAM resistant HBV. Samples were collected from 60 HBV infected patients for the analysis by allele-specific polymerase chain reaction [AS-PCR], nucleic acid detection strip [NADS] and a cross-contamination proofed device. HBV YMDD mutations were detected by AS-PCR, restriction fragment length polymorphism [RFLP] and DNA sequencing. A 91.7% concordance between all three methods was obtained. Compared to sequencing and RFLP, AS-PCR detected more samples with mutant variants and was more sensitive. This novel method had a detection limit of approximately 10[3]copies/ml and detected a variant of only 5% of total HBV population. In conclusion, we develop a new assay which could be useful for the detection of HBV LAM resistance, especially in resource-poor settings