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1.
Journal of Experimental Hematology ; (6): 1584-1587, 2023.
Article in Chinese | WPRIM | ID: wpr-1010010

ABSTRACT

Multiple myeloma (MM) is a common plasma cell malignancy, accounting for the second largest hematological malignancy. Proteasome inhibitors represented by bortezomib (BTZ) have been the main treatment for patients with newly diagnosed and relapsed or refractory myeloma in nearly two decades. Although BTZ has improved the prognosis of MM patients, MM remains incurable in most patients, mainly because MM cells become resistant to BTZ. This review is to better understand the mechanism of MM resistance to BTZ and explore possible new therapeutic strategies.


Subject(s)
Humans , Bortezomib/therapeutic use , Multiple Myeloma/pathology , Proteasome Inhibitors/pharmacology , Prognosis , Plasma Cells/pathology , Drug Resistance, Neoplasm , Antineoplastic Agents/pharmacology , Cell Line, Tumor
2.
Journal of Experimental Hematology ; (6): 1394-1402, 2023.
Article in Chinese | WPRIM | ID: wpr-1009994

ABSTRACT

OBJECTIVE@#To analyze the effects of mangiferin combined with bortezomib on the proliferation, invasion, apoptosis and autophagy of human Burkitt lymphoma Raji cells, as well as the expression of CXC chemokine receptors (CXCRs) family, and explore the molecular mechanism between them to provide scientific basis for basic research and clinical work of Burkitt lymphoma.@*METHODS@#Raji cells were intervened with different concentrations of mangiferin and bortezomib alone or in combination, then cell proliferation was detected by CCK-8 assay, cell invasion ability was detected by Transwell chamber method, cell apoptosis was detected by Annexin V/PI double-staining flow cytometry, apoptosis, autophagy and Akt/mTOR pathway protein expression were detected by Western blot, and the expression changes of CXCR family was detected by real-time quantitative PCR (RT-qPCR).@*RESULTS@#Different concentrations of mangiferin intervened Raji cells for different time could inhibit cell viability in a concentration- and time-dependent manner (r =-0.682, r =-0.836). When Raji cells were intervened by combination of mangiferin and bortezomib, compared with single drug group, the proliferation and invasion abilities were significantly decreased, while the apoptosis level was significantly increased (P <0.01). Mangiferin combined with bortezomib could significantly up-regulate the expression of pro-apoptotic protein Bax and down-regulate the expression of anti-apoptotic protein Bcl-2 after intervention in Raji cells. Caspase-3 was also hydrolyzed and activated, and then induced the apoptosis of Raji cells. Mangiferin combined with bortezomib could up-regulate the expression of LC3Ⅱ protein in Raji cells, and the ratio of LC3Ⅱ/LC3Ⅰ in cells was significantly up-regulated compared with single drug or control group (P <0.01). Mangiferin combined with bortezomib could significantly inhibit the phosphorylation levels of Akt and mTOR, inhibit the proliferation and invasion of Raji cells by inhibiting Akt/mTOR pathway, and induce cell autophagy and apoptosis. Mangiferin and bortezomib could down-regulate the expressions of CXCR4 and CXCR7 mRNA after single-agent intervention in Raji cells, and the down-regulations of CXCR4 and CXCR7 mRNA expression were more significant when the two drugs were combined (P <0.01). Mangiferin alone or combined with bortezomib had no significant effect on CXCR5 mRNA expression in Raji cells (P >0.05), while the combination of the two drugs could down-regulate the expression of CXCR3 (P <0.05).@*CONCLUSION@#Mangiferin combined with bortezomib can synergistically inhibit the proliferation and invasion of Raji cells, and induce autophagy and apoptosis. The mechanism may be related to the inhibition of Akt/mTOR signaling pathway, down-regulation of anti-apoptotic protein Bcl-2 and up-regulation of pro-apoptotic protein Bax, and the inhibition of the expression of CXCR family.


Subject(s)
Humans , Antineoplastic Agents/therapeutic use , Apoptosis/drug effects , Apoptosis Regulatory Proteins/immunology , Autophagy/immunology , bcl-2-Associated X Protein/immunology , Bortezomib/therapeutic use , Burkitt Lymphoma/immunology , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Therapy, Combination , Proto-Oncogene Proteins c-akt , Proto-Oncogene Proteins c-bcl-2 , Receptors, CXCR/immunology , RNA, Messenger , TOR Serine-Threonine Kinases , Xanthones/therapeutic use
3.
Journal of Experimental Hematology ; (6): 1750-1756, 2023.
Article in Chinese | WPRIM | ID: wpr-1010033

ABSTRACT

OBJECTIVE@#To investigate the genetic results of whole exome sequencing of bone marrow from new onset multiple myeloma (MM) patients to analyze the process of genetic clonal evolution in MM patients.@*METHODS@#Genomic DNA was extracted from bone marrow samples of 15 MM patients and the whole exomes sequencing was performed using next generation sequencing technology. Using own buccal cells as germline controls, combinated with clinical information, the mutation profile of genes from high-risk asymptomatic myeloma to symptomatic myeloma were analyzed, and genes that may be associated with the efficacy and side effects of bortezomib were screened.@*RESULTS@#Except for two patients in whom no peripheral neuropathy was observed after a short treatment period, other patients peripheral neuropathy developed of various degrees during treatment with bortezomib containing chemotherapy, and the vast majority of patients achieved remission after receiving this bortezomib-related chemotherapy regimen. All patients had comparable levels of the inherited mutations number, but the somatic mutations was correlated with disease evolution.@*CONCLUSION@#different gene "mutational spectra" exist in myeloma patients at different stages and are associated with progression through all stages of the disease.


Subject(s)
Humans , Multiple Myeloma/drug therapy , Bortezomib/therapeutic use , Bone Marrow , Exome Sequencing , Mouth Mucosa , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
4.
Journal of Experimental Hematology ; (6): 1745-1749, 2023.
Article in Chinese | WPRIM | ID: wpr-1010032

ABSTRACT

OBJECTIVE@#To establish a MM patient-derived tumor xenograft model (MM-PDX) in zebrafish, and to evaluate the anti-myeloma activity of indirubin-3'-monoxime(I3MO) using this model.@*METHODS@#Zebrafish embryos 2 days after fertilization were transplanted with fluorescence labeled myeloma primary tumor cells, the survival of primary tumor cells in zebrafish was observed at 0,16 and 24 hours after cell injection. The zebrafish embryos after tumor cell transplantation were randomly divided into control group, BTZ treatment and I3MO treatment group. Before and 24 hours after treatment with BTZ and I3MO, the positive area with calcein or Dil in zebrafish were observed under fluorescence microscope to reflect the survival of tumor cells, and it was verified.@*RESULTS@#MM patient derived tumor cells survived in zebrafish. The construction of MM-PDX was successful. Compared with control group, the fluo- rescence area of the BTZ and I3MO treatment groups in zebrafish were significantly decreased(P<0.05), and BTZ and I3MO significantly inhibited the survival of MM cells in zebrafish.@*CONCLUSION@#MM-PDX model was successfully established. Zebrafish model derived from tumor cells of MM patients can be used as a tool for drug screening of MM.


Subject(s)
Animals , Humans , Bortezomib/therapeutic use , Cell Line, Tumor , Disease Models, Animal , Drug Evaluation, Preclinical , Heterografts , Multiple Myeloma/pathology , Xenograft Model Antitumor Assays , Zebrafish
5.
Journal of Experimental Hematology ; (6): 693-698, 2023.
Article in Chinese | WPRIM | ID: wpr-982118

ABSTRACT

OBJECTIVE@#To investigate the clinical characteristics, therapeutic response and prognosis of patients with plasma cell leukemia (PCL) and improve the understanding of this disease.@*METHODS@#The clinical manifestations, laboratory tests and treatment response of 27 patients with plasma cell leukemia treated in The Second Hospital of Shanxi Medical University from December 2010 to August 2019 were analyzed retrospectively, and their clinical characteristics were summarized. Kaplan-Meier method was used for survival analysis.@*RESULTS@#There were 18 cases of primary plasma cell leukemia (pPCL) and 9 cases of secondary plasma cell leukemia (sPCL). The male to female ratio was 1.7∶1. The median age was 62 years old. The first manifestations were bone pain, fatigue, fever, splenomegaly and bleeding, and a large number of plasma cell infiltration was observed in the morphological examination of peripheral blood and bone marrow cells. 13 cases were detected by immunotyping and all of them expressed CD38/CD138. 8 cases underwent karyotype analysis, and 3 cases were normal, clonal abnormalities occurred in 5 cases. FISH detection was performed in 12 cases, of which 8 cases were abnormal. In 17 cases of bortezomib based chemotherapy, the ovevall response rate was 52.9%, which was higher than that in the non-bortezomib group, but there was no significant difference between the two groups (P =0.242). The overall median survival time of 27 patients was 6.4 months, the median progression-free survival time was 3.5 months, and the median survival time of patients with pPCL and sPCL was 8.2 months and 2.4 months, respectively, the difference between the two groups was statistically significant (P =0.031).@*CONCLUSION@#PCL is highly invasive and has diverse clinical manifestations, and is not sensitive to traditional chemotherapy. The median survival time of patients with pPCL is relatively longer than that of patients with sPCL. The chemotherapy regimen based on bortezomib improves the treatment effectiveness and prolongs the survival time of PCL patients.


Subject(s)
Male , Female , Humans , Leukemia, Plasma Cell/diagnosis , Retrospective Studies , Bortezomib/therapeutic use , Prognosis , Survival Analysis
6.
Journal of Experimental Hematology ; (6): 141-147, 2023.
Article in Chinese | WPRIM | ID: wpr-971116

ABSTRACT

OBJECTIVE@#To investigate the efficacy and safety of daratumumab in treatment of multiple myeloma (MM) patients with renal impairment (RI).@*METHODS@#The clinical data of 15 MM patients with RI who received daratumumab-based regimen from January 2021 to March 2022 in three centers were retrospectively analyzed. Patients were treated with daratumumab or daratumumab combined with dexamethasone or daratumumab combined with bortezomib and dexamethasone and the curative effect and survival were analyzed.@*RESULTS@#The median age of 15 patients was 64 (ranged 54-82) years old. Six patients were IgG-MM, 2 were IgA-MM,1 was IgD-MM and 6 were light chain MM. Median estinated glomerular filtration rate (eGFR) was 22.48 ml/(min·1.73 M2). Overall response rate of 11 patients with MM was 91% (≥MR), including 1 case of stringent complete response (sCR), 2 cases of very good partial response (VGPR), 3 cases of partial response (PR) and 4 cases of minor response (MR). The rate of renal response was 60%(9/15), including 4 cases of complete response (CR), 1 case of PR and 4 cases of MR. A median time of optimal renal response was 21 (ranged 7-56) days. With a median follow-up of 3 months, the median progression-free survival and overall survival of all patients were not reached. After treatment with daratumumab-based regimen, grade 1-2 neutropenia was the most common hematological adverse reaction. Non-hematological adverse reactions were mainly infusion-related adverse reactions and infections.@*CONCLUSION@#Daratumumab-based regimens have good short-term efficacy and safety in the treatment of multiple myeloma patients with renal impairment.


Subject(s)
Humans , Middle Aged , Aged , Aged, 80 and over , Multiple Myeloma/drug therapy , Retrospective Studies , Dexamethasone/therapeutic use , Antibodies, Monoclonal/therapeutic use , Bortezomib/therapeutic use , Renal Insufficiency/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
7.
Chinese Journal of Internal Medicine ; (12): 819-825, 2023.
Article in Chinese | WPRIM | ID: wpr-985992

ABSTRACT

Objective: To explore the stem cell collection rate and efficacy and safety of patients aged 70 and below with newly diagnosed multiple myeloma (MM) treated with the VRD (bortezomib, lenalidomide and dexamethasone) regimen followed by autologous stem cell transplantation (ASCT). Methods: Retrospective case series study. The clinical data of 123 patients with newly diagnosed MM from August 1, 2018, to June 30, 2020, at the First Affiliated Hospital of Soochow University and Suzhou Hopes Hematology Hospital, who were eligible for VRD regimen sequential ASCT, were collected. The clinical characteristics, efficacy after induction therapy, mobilization regimen of autologous stem cells, autologous stem cell collection rate, and side effects and efficacy of ASCT were retrospectively analyzed. Results: Of the 123 patients, 67 were males. The median patient age was 56 (range: 31-70) years. Patients with IgG, IgA, IgD, and light-chain types accounted for 47.2% (58/123), 23.6% (29/123), 3.2% (4/123), and 26.0% (32/123) of patients, respectively. In addition, 25.2% (31/123) of patients had renal insufficiency (creatinine clearance rate<40 ml/min). Patients with Revised-International Staging System (R-ISS) Ⅲ accounted for 18.2% (22/121) of patients. After induction therapy, the rates of partial response and above, very-good partial response (VGPR) and above, and complete response (CR)+stringent CR were 82.1% (101/123), 75.6% (93/123), and 45.5% (56/123), respectively. Overall, 90.3% (84/93) of patients were mobilized with cyclophosphamide+granulocyte colony-stimulating factor (G-CSF) and 8 patients with G-CSF or G-CSF+plerixafor due to creatinine clearance rate<30 ml/min and one of them was mobilized with DECP (cisplatin, etoposide, cyclophosphamide and dexamethasone)+G-CSF for progressive disease. The rate of autologous stem cell collection (CD34+cells≥2×106/kg) after four courses of VRD regimen was 89.1% (82/92), and the rate of collection (CD34+cells≥5×106/kg) was 56.5% (52/92). Seventy-seven patients treated with the VRD regimen sequential ASCT. All patients had grade 4 neutropenia and thrombocytopenia. Among the nonhematologic adverse events during ASCT, the highest incidence was observed for gastrointestinal reactions (76.6%, 59/77), followed by oral mucositis (46.8%, 36/77), elevated aminotransferases (44.2%, 34/77), fever (37.7%, 29/77), infection (16.9%, 13/77) and heart-related adverse events (11.7%, 9/77). Among the adverse events, grade 3 adverse events included nausea (6.5%, 5/77), oral mucositis (5.2%, 4/77), vomiting (3.9%, 3/77), infection (2.6%, 2/77), elevated blood pressure after infusion (2.6%, 2/77), elevated alanine transaminase (1.3%, 1/77), and perianal mucositis (1.3%, 1/77); there were no grade 4 or above nonhematologic adverse events. The proportion of patients who achieved VGPR and above after VRD sequential ASCT was 100% (75/75), and the proportion of patients who were minimal residual disease-negative (<10-4 level) was 82.7% (62/75). Conclusion: In patients aged 70 and below with newly diagnosed MM treated with VRD induction therapy, the collection rate of autologous stem cells was good, and good efficacy and tolerability were noted after follow-up ASCT.


Subject(s)
Male , Humans , Female , Multiple Myeloma/diagnosis , Hematopoietic Stem Cell Transplantation/adverse effects , Retrospective Studies , Creatinine , Hematopoietic Stem Cell Mobilization , Transplantation, Autologous , Dexamethasone/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Heterocyclic Compounds/therapeutic use , Bortezomib/therapeutic use , Cyclophosphamide/therapeutic use , Stomatitis/etiology
8.
Chinese Journal of Hematology ; (12): 413-417, 2023.
Article in Chinese | WPRIM | ID: wpr-984638

ABSTRACT

Objective: To observe the efficacy and adverse reactions of a combination therapy regimen based on bortezomib and glucocorticoids in recurrent/refractory immune thrombocytopenic purpura (iTTP) . Methods: Six patients with recurrent/refractory TTP were included and treated with a glucocorticoid and two courses of bortezomib-based regimen. The clinical remission status of patients, changes in ADAMTS13 activity/ADAMTS13 inhibitor, and the occurrence of treatment-related adverse reactions were observed. Results: Of the 6 patients, 2 were males and 4 were females, with a median age of 21.5 (18-68) years. Refractory TTP was found in 1 case and recurrent TTP in 5 cases. Glucocorticoids were administered with reference to prednisone at 1 mg·kg(-1)·d(-1), and gradually reduced in dosage after achieving clinical remission. Bortezomib is subcutaneously administered at 1.3 mg/m(2) on days 1, 4, 8, and 11 with a 28-day treatment course consisting of 2 courses. Six patients achieved clinical remission after receiving bortezomib as the main treatment. ADMATS13 activity returned to normal in all patients with TTP after treatment, and the ADAMTS13 inhibitor turned negative. Thrombocytopenia is the most common adverse reaction after treatment, with other adverse reactions, including peripheral neuritis and abdominal pain, but ultimately all patients returned to normal. In a median follow-up of 26 (9-41) months, 5 patients maintained sustained remission, and 1 patient relapsed after 16 months of bortezomib treatment. Conclusion: Combination therapy of bortezomib and glucocorticoids has a satisfactory therapeutic effect and controllable adverse reactions for recurrent/refractory iTTP.


Subject(s)
Male , Female , Humans , Young Adult , Adult , Middle Aged , Aged , Bortezomib/therapeutic use , Glucocorticoids/therapeutic use , Rituximab/therapeutic use , Purpura, Thrombotic Thrombocytopenic/drug therapy , Purpura, Thrombocytopenic, Idiopathic/drug therapy , ADAMTS13 Protein/therapeutic use
9.
Chinese Journal of Hematology ; (12): 141-147, 2023.
Article in Chinese | WPRIM | ID: wpr-969690

ABSTRACT

Objective: To investigate the causative factors of renal function in newly diagnosed multiple myeloma (MM) patients with renal inadequacy. Methods: 181 MM patients with renal impairment from August 2007 to October 2021 at Peking Union Medical College Hospital were recruited, whose baseline chronic kidney disease (CKD) stage was 3-5. Statistical analysis was performed based on laboratory tests, treatment regimens, hematological responses, and survival among various renal function efficacy groups. A logistic regression model was employed in multivariate analysis. Results: A total of 181 patients were recruited, and 277 patients with CKD stages 1-2 were chosen as controls. The majority choose the BCD and VRD regimens. The progression-free survival (PFS) (14.0 months vs 24.8 months, P<0.001) and overall survival (OS) (49.2 months vs 79.7 months, P<0.001) of patients with renal impairment was considerably shorter. Hypercalcemia (P=0.013, OR=5.654) , 1q21 amplification (P=0.018, OR=2.876) , and hematological response over a partial response (P=0.001, OR=4.999) were independent predictive factors for renal function response. After treatment, those with improvement in renal function had a longer PFS than those without (15.6 months vs 10.2 months, P=0.074) , but there was no disparity in OS (56.5 months vs 47.3 months, P=0.665) . Conclusion: Hypercalcemia, 1q21 amplification, and hematologic response were independent predictors of the response of renal function in NDMM patients with renal impairment. MM patients with CKD 3-5 at baseline still have worse survival. Improvement in renal function after treatment is attributed to the improvement in PFS.


Subject(s)
Humans , Multiple Myeloma/drug therapy , Bortezomib/therapeutic use , Hypercalcemia , Prognosis , Chromosome Aberrations , Kidney/physiology , Renal Insufficiency, Chronic , Retrospective Studies , Antineoplastic Combined Chemotherapy Protocols
10.
Rev. med. Chile ; 150(6): 832-835, jun. 2022. ilus
Article in Spanish | LILACS | ID: biblio-1424127

ABSTRACT

Multiple Myeloma (MM) is characterized by a clonal expansion of plasma cells in the bone marrow. These cells typically produce a monoclonal immunoglobulin, and its symptoms arise either from plasma cell infiltration in several organs, or secondary to the presence of a monoclonal protein peak. Symptoms can be summarized by the acronym CRAB (hypercalcemia, renal failure, anemia and bone lesions). Sometimes, in the setting of a protein secreting monoclonal gammopathy, formation of cryoglobulins develops. Cryoglobulins are plasma proteins that precipitate at low temperatures, forming a cold - induced precipitate at small vessels, causing a wide range of clinical manifestations. We report a female consulting for ulcers lasting 2 months in the left foot associated with purpuric lesions in both lower limbs. Protein electrophoresis showed a monoclonal peak in the gamma region. Bone marrow aspirate showed 27% of plasma cells with kappa chain restriction by cytometry. The presence of cryoglobulins was confirmed. The patient was treated with dexamethasone and bortezomib, with a progressive healing of lower limb lesions and disappearance of cryoglobulins. She was discharged in good conditions.


Subject(s)
Humans , Female , Vasculitis/complications , Cryoglobulinemia/complications , Cryoglobulinemia/diagnosis , Multiple Myeloma/complications , Multiple Myeloma/diagnosis , Cryogels , Bortezomib/therapeutic use
11.
Rev. méd. Chile ; 150(3): 331-338, mar. 2022. tab, graf
Article in Spanish | LILACS | ID: biblio-1409806

ABSTRACT

BACKGROUND: The incorporation of novel drugs, such as proteasome inhibitors and immunomodulators, improved considerably the survival of patients with multiple myeloma. Aim: To evaluate the effect on survival of proteasome inhibitors and immunomodulators in patients with multiple myeloma in two national hospitals. MATERIAL AND METHODS: Review of clinical records from two hospitals of Santiago. Epidemiological, clinical, laboratory and therapeutic data was obtained from 144 patients with multiple myeloma diagnosed between 2002 and 2016. Results: Information was retrieved from 78 patients at one center and from 66 at the other center. The mean age at diagnosis was 58 and 62 years, the proportion of males was 53% and 52%, and presentation at stage III was 34% and 46%, respectively. The use of novel drugs, mainly bortezomib, was 90% in one of the centers and 3% in the other one. The use of autologous stem-cell transplantation was 47% and 3% respectively. The median overall survival of patients from the centers with and without access to novel drugs was 117 and 71 months respectively (p < 0.05). The five-year overall survival was 93 and 43% respectively (p < 0.05). CONCLUSIONS: The use of novel drugs, especially bortezomib, and autologous stem-cell transplantation significantly improved the survival of multiple myeloma patients treated in national hospitals. It is necessary to include them as a first line treatment.


Subject(s)
Humans , Male , Hematopoietic Stem Cell Transplantation , Multiple Myeloma/diagnosis , Transplantation, Autologous , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chile/epidemiology , Proteasome Inhibitors/therapeutic use , Bortezomib/therapeutic use
12.
São Paulo med. j ; 140(2): 222-228, Jan.-Feb. 2022. tab, graf
Article in English | LILACS | ID: biblio-1366039

ABSTRACT

Abstract BACKGROUND: In this era of target therapies, novel data on the correlation between response endpoints and survival outcomes in multiple myeloma have arisen. OBJECTIVE: To determine the impact of quality of response on clinical outcomes, using first-line treatment, and identify risk factors influencing progression-free survival (PFS) and overall survival (OS) among myeloma patients. DESIGN AND SETTING: Retrospective analysis on myeloma patients who were treated at the Clinic of Hematology and Clinical Immunology, University Clinical Centre, Niš, Serbia, over a four-year period. METHODS: A total of 108 newly diagnosed patients who received first-line therapy consisting of conventional chemotherapy or novel agent-based regimens were included in this analysis. RESULTS: The quality of response to first-line therapy for the whole cohort was classified as follows: complete response (CR) in 19%; very good partial response (VGPR) in 23%; partial response (PR) in 38%; and less than PR for the remaining patients. After a median follow-up of 25.4 months, the three-year PFS and OS for the entire study population were 47% and 70%, respectively. Achievement of CR was the main factor associated with significantly prolonged PFS and OS, in comparison with patients who reached VGPR and PR. Likewise, addition of the new drugs bortezomib and thalidomide to standard chemotherapy led to considerably extended PFS and OS, compared with conventional therapy alone. CONCLUSIONS: This analysis demonstrated that the quality of response after application of first-line treatment using novel agent-based regimens among multiple myeloma patients was a prognostic factor for PFS and OS, which are the most clinically relevant outcomes.


Subject(s)
Multiple Myeloma/drug therapy , Remission Induction , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Retrospective Studies , Treatment Outcome , Serbia , Bortezomib/therapeutic use
13.
Chinese Journal of Hematology ; (12): 414-419, 2022.
Article in Chinese | WPRIM | ID: wpr-929629

ABSTRACT

Objective: To establish three types of xenotransplantation models using human myeloma cell lines ARP1, MM.1S, and NCI-H929 and to compare the proliferation, tumor load, and biological characteristics of the three types of cells after transplantation. Methods: Suspensions of human myeloma cell lines ARP1, MM.1S, and NCI-H929 were implanted into NOD/SCID mice by subcutaneous injection or tail vein injection. The survival of the mice was observed weekly, and the tumor load was measured. Flow cytometry was used to detect the proportion of CD138(+) cells in tumor tissue or the mouse bone marrow. CD138(+) cells and light chains were detected by immunofluorescence. Light chains in bone marow and peipheral blood were measured by ELISA, and bone disease was assessed by micro-CT. Results: Mice injected with ARP1, MM.1S, and NCI-H929 cells all formed tumors subcutaneously in about 2 weeks. Immunofluorescence detection supported plasma cell tumors. Kappa light chains were detected in the peripheral blood of ARP1 mice on day 20 after tail vein transplantation (8.2±1.0 ng/ml) . After 6 weeks of tail vein transplantation, mice in the ARP1 group showed signs of weight loss, mental depression, and dragging legs, and human CD138(+)CD38(+) cells were detected in the bone marrow (BM) . Furthermore, bortezomib (BTZ) treatment given once the tumor was established significantly reduced the tumor burden[ (5.7±0.2) % vs (21.3±2.1) %, P<0.01]. Human CD138(+)CD38(+) cells were not detected in the BM of the MM.1S or NCI-H929 groups. Conclusion: The results of this study suggest that the mouse models constructed by the three cell lines (ARP1, MM.1S, and NCI-H929) can be used as models for the pathogenesis and clinical research of MM.


Subject(s)
Animals , Humans , Mice , Bortezomib/therapeutic use , Cell Line, Tumor , Disease Models, Animal , Mice, Inbred NOD , Mice, SCID , Multiple Myeloma/drug therapy
14.
Journal of Experimental Hematology ; (6): 481-486, 2022.
Article in Chinese | WPRIM | ID: wpr-928740

ABSTRACT

OBJECTIVE@#To investigate the prognostic value of hemopoietic scoring system composed of hemoglobin (HB), platelet count (PLT) and mean corpuscular volume (MCV) in MM patients and its correlation with curative effect.@*METHODS@#The clinical data of 172 newly diagnosed MM patients treated by bortezomib as the first-line regimen in our hospital from May 2014 to December 2019 were collected, three variables (HB≤100 g/L, PLT≤150×109/L, MCV≥96 fl) were introduced, each variable was distributed 1 score, the patients were divided into four groups (0, 1, 2 and 3 points in group 1, 2, 3 and 4, respectively), and the clinical characteristics and prognosis of the patients in the four groups were analyzed. The initial efficacy evaluation after 3-4 courses of treatment was carried out, and the curative effect of the patients in the different hematopoiesis score groups were compared.@*RESULTS@#The median OS time of the patients in group 1, 2, 3 and 4 was 27.0, 22.5, 20.7 and 18.1 months, while the median PFS time were 23.0, 19.0, 18.0 and 14.0 months, respectively. The OS and PFS of the patients in low score group were significantly better than those in high score group (P=0.045, P=0.048). There was no significant difference in the curative effect of the patients treated by bortezomib after 3-4 courses (P>0.05).@*CONCLUSION@#Hematopoiesis score can preliminarily predict the overall survival of newly diagnosed MM patients, but there is no significant difference between different scoring groups in the initial curative effect.


Subject(s)
Humans , Bortezomib/therapeutic use , Erythrocyte Indices , Hemoglobins/therapeutic use , Multiple Myeloma/diagnosis , Prognosis , Retrospective Studies
15.
Journal of Experimental Hematology ; (6): 145-151, 2021.
Article in Chinese | WPRIM | ID: wpr-880045

ABSTRACT

OBJECTIVE@#To explore the risk factors, prognosis and curative effect of elderly patients with MM renal damage.@*METHODS@#118 patients with primary elderly MM treated in our hospital from January 2011 to December 2018, were enrolled analyzed retrospectively. The clinical characteristics and prognosis of renal function impairment group (RI group) and normal renal function group (non-RI group) were compared. The difference of renal efficacy and survival benefit between the patients treated with bortezomib, thalidomide (combination group) and chemotherapy regimen containing only one of them (single drug group) in RI group was compared.@*RESULTS@#Univariate analysis showed that DS stage, pulmonary infection, uric acid, β @*CONCLUSION@#The prognosis of elderly MM patients with impaired renal function is poor. The prognosis of these patients can be improved by selecting chemotherapy regimen containing bortezomib and thalidomide at the same time, and monitoring, controlling all kinds of risk factors actively.


Subject(s)
Aged , Humans , Antineoplastic Combined Chemotherapy Protocols , Bortezomib/therapeutic use , Multiple Myeloma/drug therapy , Prognosis , Retrospective Studies , Treatment Outcome
16.
Journal of Experimental Hematology ; (6): 137-144, 2021.
Article in Chinese | WPRIM | ID: wpr-880044

ABSTRACT

OBJECTIVE@#To investigate the short-term efficacy and safety of generic bortezomib in the treatment of Chinese patients with multiple myeloma (MM).@*METHODS@#Clinical data of 62 MM patients (median age of 62 years) who had accepted at least 2 cycles of chemotherapy based on generic bortezomib in our center from December 2017 to July 2019 were retrospectively analyzed, including 47 newly diagnosed patients and 15 with disease recurrence or progression.@*RESULTS@#Anemia, renal dysfunction, hypoproteinemia and high level of β @*CONCLUSION@#The disease severity can be rapidly alleviated after generic bortezomib-based chemotherapy, and a favorable short-term efficacy and survival have been observed with a generally acceptable toxicity profile. However, the long-term outcomes will be examined through further follow-up.


Subject(s)
Humans , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bortezomib/therapeutic use , Dexamethasone/therapeutic use , Disease-Free Survival , Multiple Myeloma/drug therapy , Neoplasm Recurrence, Local , Retrospective Studies , Transplantation, Autologous , Treatment Outcome
17.
Journal of Experimental Hematology ; (6): 131-136, 2021.
Article in Chinese | WPRIM | ID: wpr-880043

ABSTRACT

OBJECTIVE@#To investigate the efficacy, survival and adverse effects of non-transplanted multiple myeloma (MM) patients treated with bortezomib maintenance.@*METHODS@#A total of 25 newly diagnosed/relapsed non-transplanted MM patients treated in West District of Beijing Chaoyang Hospital from June 2004 to November 2015 were analyzed retrospectively. All patients received PD regimen (bortezomib and dexamethasone), including bortezomib at a dose of 1.3 mg/m@*RESULTS@#Till November 1, 2017, 5 patients achieved stringent complete response (sCR), 8 patients achieved complete response (CR), 7 patients achieved very good partial response (VGPR), 4 patients achieved partial reponse (PR), while 1 patient achieved stable disease (SD). After maintenance therapy, 21 patients maintained the efficacy above PR, of which 1 patient was improved from CR to sCR; 4 patients adjusted chemotherapy after disease progressed. Median maintenance therapy was 9 cycles (range from 6 to 31), and the median maintenance time was 27 months (range from 18 to 97). Median follow-up time was 73 months (range from 25 to 171). Median progress-free survival (PFS) time was 30 months (range from 9 to 105) and overall survival (OS) time was 57 months (range from 27 to 160). Till November 1, 2019, 3-year survival rate was 84% (21/25), and 5-year survival rate was 72% (13/18). The most common adverse events were transient leukopenia, thrombocytopenia and peripheral neuropathy, which the patients could tolerate after the prevention and treatment.@*CONCLUSION@#Bortezomib-based maintenance therapy for non-transplanted MM patients can be an option in consideration of its safety and efficacy.


Subject(s)
Humans , Antineoplastic Combined Chemotherapy Protocols , Bortezomib/therapeutic use , Dexamethasone/therapeutic use , Disease-Free Survival , Multiple Myeloma/drug therapy , Retrospective Studies , Treatment Outcome
19.
Rev. cuba. hematol. inmunol. hemoter ; 35(3): e1067, jul.-set. 2019.
Article in Spanish | CUMED, LILACS | ID: biblio-1093277

ABSTRACT

Introducción: El mieloma múltiple (MM) es una enfermedad que va precedida por una fase previa conocida como gammapatía monoclonal de significado incierto (GMSI); en esta última existen varias anormalidades citogenéticas, que permiten la progresión a MM, entre estas encontramos reordenamientos primarios del gen de la cadena pesada de la inmunoglobina (IGH), además de células hiperdiploides. Desarrollo: Las alteraciones cromosómicas en el MM se pueden clasificar en dos grupos principales: las que involucran las translocaciones del locus IGH ubicado en el cromosoma 14q32 y cuyos principales reordenamientos se dan entre las regiones cromosómicas 11q13, 16q23, 4p16.3, 6p21 y, un segundo grupo caracterizado por los desequilibrios genómicos. Los pacientes con translocaciones de la IGH, muestran un pronóstico diferente en dependencia del tipo de reordenamiento cromosómico. La t(4;14)(p16;q32) y t(14;16)(q32;q23) se asocian a un mal pronóstico, mientras que los pacientes con t(11;14) (q13;q32) tiene un buen pronóstico de la enfermedad en ausencia de otras anormalidades genéticas. En el grupo con desequilibrio genómico se encuentran deleciones, amplificaciones, y células con números anormales de cromosomas (hiperdiploidas y no hiperdiploides); casi siempre asociadas a mal pronóstico ya que muchas de estas alteraciones involucran perdida de material genómico relacionado con el control de ciclo celular y progresión de la enfermedad, como son las deleciones de los cromosomas 1,13 y 17. Los pacientes con trisomías de los cromosomas impares 1, 3, 5, 7, 9, 11, 15, 19,21 suelen tener un mejor pronóstico y una tasa mayor de sobrevivencia(AU)


Introduction: Multiple myeloma (MM) is a disease that is preceded by a previous phase known as monoclonal gammopathy of uncertain significance (MGUS); in this latter there are several cytogenetic abnormalities, which allow the progression to MM, among these we find primary rearrangements of the heavy chain gene of the immunoglobin (IGH), in addition to hyperdiploid cells. Development: Chromosomal alterations in MM can be classified into two main groups, those involving the translocations of the IGH locus located on chromosome 14q32 and whose main rearrangements occur between the chromosomal regions 11q13, 16q23, 4p16.3, 6p21, and a second group which is characterized by genomic imbalances. Patients with translocations of the IGH, show a different prognosis depending on the type of chromosomal rearrangement, the t(4; 14)(p16; q32) and t(14; 16)(q32; q23) are associated with a poor prognosis while patients with t(11; 14)(q13; q32) have a good prognosis of the disease in the absence of other genetic abnormalities. Within the genomic imbalances we find deletions, amplifications, and cells with abnormal numbers of chromosomes (hyperdiploids and not hyperdiploid), these almost always associated with poor prognosis since many of these alterations involve loss of genomic material related to cell cycle control and progression of the disease, such as deletions of chromosomes 1,13 and 17. Patients with trisomies of odd chromosomes 1, 3, 5, 7, 9, 11, 15, 19,21 usually have a better prognosis and a higher survival rate(AU)


Subject(s)
Humans , Male , Female , Prognosis , Multiple Myeloma/genetics , Multiple Myeloma/epidemiology , Paraproteinemias/genetics , Chromosome Deletion , Disease Progression , Cytogenetic Analysis/methods , Bortezomib/therapeutic use
20.
Chinese Journal of Hematology ; (12): 584-588, 2019.
Article in Chinese | WPRIM | ID: wpr-1012191

ABSTRACT

Objective: To evaluate the prognostic value of kinetic changes in minimal residual disease (MRD) status, as well as its relationship with risk stratification, therapeutic response and treatment in patients with newly-diagnosed multiple myeloma (MM) . Methods: A total of 135 patients with newly-diagnosed MM were screened, and 105 patients who achieved VGPR or more as the best responses were included into this study. The MRD status was determined by multiparameter flow cytometry (MFC) at multiple intervals after two cycles of treatment until clinical relapse, death, or last follow-up. The statistical methods included Kaplan-Meier analysis, Cox regression, etc. Results: ①In all 135 patients, 57.8% (78/135) patients achieved MRD negativity (MRD(-)) after treatment. In 105 patients who achieved VGPR and thus included in this study, the MRD(-) rate was 72.4% (76/105) , with a median interval of 3 months from starting treatment to achievement of MRD(-) status. ②The 2-year PFS rate of patients with MRD(-) status was significantly higher than that of MRD(+) status (62.2% vs 41.3%, P=0.001) , while MRD persistence (MRD(+)) was an independent factor for poor prognosis (multivariate analysis for PFS: P=0.044, HR=3.039, 95%CI 1.029-8.974) . ③Loss of MRD(-) status (i.e., MRD reappearance) showed inferior outcomes compared with MRD sustained negative ones, the PFS was 18 months versus not reach (P<0.001) and the OS was not reach for both (P=0.002) . ④The 2-year PFS and OS rates of patients with duration of MRD(-)status≥12 months were significantly higher than those of the control group (PFS: 77.7% vs 36.7%, P<0.001; OS: 96.4% vs 57.9%, P<0.001 respectively) . Duration of MRD(-) status was associated with a marked reduction in risk of relapse or death (univariate analysis for PFS: P<0.001, HR=0.865, 95%CI 0.815-0.918; for OS: P=0.001, HR=0.850, 95%CI 0.741-0.915 respectively) . ⑤Moreover, even in patients carrying high-risk cytogenetic abnormalities (CA) or ineligible for ASCT, MRD negativity remained its prognostic value to predict PFS (high-risk CA medianPFS: not reach vs 19 months, P=0.006; ineligible for ASCT medianPFS: not reach vs 25 months, P=0.052 respectively) . ⑥Last, treatment with the bortezomib-based regimens contributed to prolonged MRD(-) duration (median MRD(-) duratio: 25 months vs 10 months, P=0.034) . Conclusion: Our findings supported MRD(+) status as an independent poor prognostic factor in MM patients, which implicated that duration of MRD(-) status also played a significant role in evaluation of prognosis, while loss of MRD(-)status might serve as an early biomarker for relapse. Therefore, monitoring of MRD kinetics might more precisely predict prognosis, as well as guide treatment decision, especially for when to start retreatment in relapsed patients.


Subject(s)
Humans , Bortezomib/therapeutic use , Multiple Myeloma/therapy , Neoplasm Recurrence, Local , Neoplasm, Residual/diagnosis , Prognosis , Risk Assessment , Treatment Outcome
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