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Objective:To verify the predictive value of the Second Revision of the International Staging System (R2-ISS) in newly diagnosed patients with multiple myeloma (MM) who underwent first-line autologous hematopoietic stem cell transplantation (ASCT) in a new drug era in China.Methods:This multicenter retrospective cohort study enrolled patients with newly diagnosed MM from three centers in China (Beijing Chao-Yang Hospital, Capital Medical University; the First Affiliated Hospital, Sun Yat-Sen University, and the Second Affiliated Hospital of Naval Medical University) from June 2008 to June 2018. A total of 401 newly diagnosed patients with MM who were candidates for ASCT were enrolled in this cohort, all received proteasome inhibitor and/or immunomodulator-based induction chemotherapy followed by ASCT. Baseline and follow-up data were collected. The patients were regrouped using R2-ISS. Progression-free survival (PFS) and overall survival (OS) were analyzed. The Kaplan-Meier method was used to analyze the survival curve and two survival curves were compared using the log-rank test. Cox regression analysis were performed to analyze the relationship between risk factors and survival.Results:The median age of the patients was 53 years (range 25-69 years) and 59.5% (240 cases) were men. Newly diagnosed patients with renal impairment accounted for 11.5% (46 cases). According to Revised-International Staging System (R-ISS), 74 patients (18.5 %) were diagnosed with stage Ⅰ, 259 patients (64.6%) with stage Ⅱ, and 68 patients (17.0%) with stage Ⅲ. According to the R2-ISS, the distribution of patients in each group was as follows: 50 patients (12.5%) in stage Ⅰ, 95 patients (23.7%) in stage Ⅱ, 206 patients (51.4%) in stage Ⅲ, and 50 patients (12.5%) in stage Ⅳ. The median follow-up time was 35.9 months (range, 6-119 months). According to the R2-ISS stage, the median PFS in each group was: 75.3 months for stage Ⅰ; 62.0 months for stage Ⅱ, 39.2 months for stage Ⅲ, and 30.3 months for stage Ⅳ; and the median OS was not reached, 86.6 months, 71.6 months, and 38.5 months, respectively. There were statistically significant differences in PFS and OS between different groups (both P<0.001). Multivariate Cox regression analysis showed that stages Ⅲ and Ⅳ of the R2-ISS were independent prognostic factors for PFS ( HR=2.37, 95% CI 1.30-4.30; HR=4.50, 95% CI 2.35-9.01) and OS ( HR=4.20, 95% CI 1.50-11.80; HR=9.53, 95% CI 3.21-28.29). Conclusions:The R2-ISS has significant predictive value for PFS and OS for transplant-eligible patients with MM in the new drug era. However, the universality of the R2-ISS still needs to be further verified in different populations.
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Objective:To investigate the clinical features and prognosis of multiple myeloma(MM)patients who resisted to the combination of bortezomib,lenalidomide and dexamethasone(VRD). Methods:The clinical features and prognosis of 150 patients with newly diagnosed MM in Beijing Chaoyang Hospital who were treated with VRD from January 2015 to January 2020 were retrospectively analyzed by SPSS software. Results:Among a total of 150 MM patients,21 patients resisted to VRD,including 14 patients with primary refractory to VRD and 7 patients with early relapse.In the VRD-resistant group(n=21),the median age of patients was 58 years(37-70 years),and female patients were more common(61.9%);Durie-Salmon stage:17 patients were DS stage Ⅲ,4 patients were DS stage Ⅱ;44.4%of those patients were cytogenetic high risk.CD20 positive rate was higher in the VRD-resistant group(P=0.014).The overall survival(OS)of MM patients in the VRD-resistant group was significantly lower than that in the VRD-nonresistant group(34 months vs not achieved,P<0.001).In the VRD-resistant group,the median OS of MM patients receiving autologous hematopoietic stem cell transplantation was significantly longer than that of non-transplant patients(34 months vs 16 months,P=0.038).Drug resistance and non-autologous transplantation are independent adverse prognostic factors for newly diagnosed MM patients receiving VRD induction chemotherapy.COX multivariate analysis showed that age>65,cytogenetic high risk and non-autologous stem cell transplantation may be adverse prognostic factors for VRD-resistant MM patients. Conclusion:Positive CD20 was more common in MM patients with VRD resistence,which may indicate more aggressive biological characteristics in VRD-resistent MM patients.The VRD-resistent MM patients had poor prognosis,they can obtain disease remission from salvage chemotherapy including daratumumab,and the survival of them also can be improved after autologous stem cell transplantation.
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Objective:To evaluate the prognostic value of CD56 expression in newly diagnosed MM (NDMM).Methods:A total of 332 NDMM patients were enrolled in Beijing Chaoyang Hospital, Capital Medical University from January 1, 2011 to January 1, 2021, with a median age of 60 years and a male to female ratio of 1.2∶1. CD56 expression on myeloma cells was detected by flow cytometry before induction therapy. Overall survival (OS) and progression-free survival (PFS) data were collected. In order to reduce the confounding factors, the propensity score matching technique was used to match CD56 positive versus negative patients at a ratio of 1∶1.Results:Among 332 patients, CD56 positivity rate was 65.1% (216/332). Patients with CD56 expression had significantly longer median OS (58.4 vs. 43.1 months, P=0.024) and PFS (28.7 vs. 24.1 months, P=0.013) than those with negative CD56. Univariate Cox proportional hazards regression analyses showed that CD56 expression was positively correlated with OS ( HR=0.644, 95 %CI 0.438-0.947, P=0.025) and a favorable prognostic factor for PFS ( HR=0.646, 95 %CI 0.457-0.913, P=0.013). The favorable effect of CD56 expression on PFS was confirmed in multivariate analysis ( HR=0.705, 95 %CI 0.497-0.998, P=0.049), but OS was not affected ( P>0.05).In the propensity score matching analysis, 194 patients with 97 in each group were identified. CD56 positivity consistently predicted longer PFS (34.2 vs.25.1 months, P=0.047), but not OS (63.4 vs.43.1 months, P=0.056). Conclusion:These results demonstrate that CD56 expression is a favorable prognostic factor for PFS of newly diagnosed MM patients.
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Objective@#To compare the sensitivity of 8-color panels and next generation flow cytometry (NGF) for detecting minimal residual disease of multiple myeloma patients.@*Methods@#8-color-membrane antigens (8C-Mem) panel was built including CD45, CD38, CD138, CD19, CD56, CD81, CD27 and CD117 to identify the plasma cells, while 8-color-cytoplasmic antigens (8C-Cyto) panel was built including CD45, CD38, CD138, CD19, CD56, CD81, cKappa (cK) and cLambda (cλ) , and 8-color-two-tubes (8C-2tubes) panel were built including 8C-Mem and 8C-Cyto panels, the data of three groups was analyzed by Diva software. NGF uses Infinicyt software to fuse 8C-2tubes data to further analyze the expression of plasma antigens. Bone marrow aspiration obtained from 20 controls and 76 multiple myeloma patients who achieved complete remission were measured and analyzed.@*Results@#Positive MRD samples were discriminated in 88.2% of the specimen evaluated through either abnormal plasma cells (aPCs) or clonal plasma cells (cPCs) by NGF antigens panel, Among of them, consistency was 94.7%. The median percentage of cPCs was 0.3530%, The lowest sensitivity of NGF was 0.0003%. In 8-color panels, the positive MRD rates of 8C-Mem, 8C-Cyto and 8C-2tubes panels were 84.2%, 85.5% and 86.8%, respectively, which lower than that of NGF (P<0.001) . The positive MRD rate of 8C-Mem and 8C-Cyto panels were lower than that of 8C-2tubes panel (P<0.001) , and the positive MRD rate of 8C-Mem panel was lower than that of 8C-Cyto panel (P<0.001) . Sensitivity and specificity of NGF was higher than that of 8-color panels. 8C-2tubes panel has the best sensitivity, accuracy, negative predicted value, positive predicted value and specificity than other 8-color panels. However, huge data and low efficiency for analysis is the disadvantage. 8C-Cyto panel was the second choice, and 8C-Mem panel was the last.@*Conclusions@#Membrane and cytoplasmic light chain is a better method for multiple myeloma-MRD detection and NGF panel is an ideal approach. 8C-Cyto panel is recommended in 8-MFC groups.
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Bruton tyrosine kinase (BTK) is a non-receptor tyrosine kinase which belongs to the Tec kinase family and plays an important role in B cell receptor signaling.Nowadays,BTK has been a nove] target for treating some B cell malignancies.Recently,some studies have confirmed that BTK inhibitor,PCI-32765 (ibrutinib),can effectively treat chronic lymphocytic leukemia,mantle cell lymphoma and so on.This review will discuss the preclinical and clinical development of this BTK inhibitor in B cell malignancies.
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The 48th annual meeting of the American Society of Clinical Oncology (ASCO) was held in Chicago from June 1-5 2012 and the risk-adapted therapy of multiple myeloma (MM) was discussed.MM is a heterogeneous disease and all patients should be accepted risk-adapted therapy. According to cytogenetic abnormalities, MM patients are divided into three groups,standard risk, intermediate risk and high risk.Patients with standard risk may received 4 cycles Rd regimes (lenalidomide plus low dose dexamethasone) or VCD regimes (bortezomib,cyclophosphamide,dexamethasone) for induction therap.Patients with intermediate risk may received 4 cycles VCD regimes for induction therapy.Patients with high risk may received 4 cycles VRD regimes (bortezomib,lenalidomide,dexamethasone) for induction therapy.After induction treatment,patients can received autologous hematopoietic cell transplantation or consolidation/maintenance therapy. The determination of which patients are eligible for autologous hematopoietic cell transplantation according age,comorbidities and performance status.
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Hematopoietic cell transplantation is frontline treatment of multiple myeloma (MM).Autologous hematopoietic stem cell transplantation (auto-HSCT) could improve remission rate,prolong survival time,the tandem auto-HSCT is able to make patients get further benefits for patients not achieving at least very good partial remission after the first auto-HSCT.Allologous hematopoietic stem cell transplantation (alloHSCT) is potentially able to cure multiple myeloma,but patients achieve less benefit because of high transplant-related mortality (TRM).The TRM is low after reduced-intensity conditioning allo-HSCT,but which exhibit no survival benefit.Moreover,patients achieve no survival benefit after tandem auto-HSCT and allologous reduced-intensity conditioning transplantation.This paper reviewes recent studies about HSCT in MM.
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Multiple myeloma is a malignancy of plasma cells and renal function impairment is one of common complications of multiple myeloma.Light-chain deposition in renal tubules which induces renal tubular disease is the major pathogenesis of renal impairment.The renal function impairment should be estimated based on glomerular filtration rate in multiple myeloma patients. Bortezomib with high-dose dexamethasone is effective to myeloma patients with renal impairment and improves renal function.Treatment experience of thalidomide is limited,but it can be used at the standard dosage to patients with renal failure.Lenalidomide is effective and can reverse renal impairment of several myeloma patients when this agent is used at reduced doses according to renal function.
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Many complex symptoms are observed in multiple myeloma and the most common symptom is bone damage, decreased renal function, increased infection susceptibility, anemia and peripheral neuropathy. Moreover some patients have other accompanying disease, such plasmacytoma and amyloidosis.Symptoms in multiple myeloma are the important basis for initiating anti-myeloma therapy. This paper is to review the pathophysiology of the complication of multiple myeloma and its treatment.
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@#Objective To screen the optimum conditions carrying murine melanoma B16 cells in spaceflights without cares.MethodsMurine melanoma cells were cultured on micocarriers and grouped depending on cells concentration, serum concentration, microcarrier number and temperature.After 33 days, B16 cells were stained by Giemsa, observed with phase-contrast microscope and counted for surviving percentage.ResultsThe optimum conditions,in which the surviving percentages were 8% and 10%, were obtained in the experiments.B16 cells were carried in the 20th recoverable satellite orbiting 18 days under the optimum conditions. After recovering, 110 strain monocloned cells were survived and the surviving percentage was 1.1%.ConclusionThe optimum conditions carrying murine melanoma B16 cells in spaceflights without cares seems to be obtained,and it did improve the surviving time and percentage of cells in spaceflights without cares.
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@#ObjectiveTo search for a new method of anti-tumor immunity,using mutated tumor cells by spaceflight.MethodsTumor cells were carried in the Shenzhou 4 and the recoverable satellite No.18.After 7 days and 18 days spaceflight respectively,the effects of spaceflight were investigated primarily.Results2382 and 1 strains of mutated tumor cells from the airship No.4 and the recoverable satellite No.18 had been obtained respectively. Comparing with the control group, the growth rate of mutated cells decreased, moreover, the secretion of cytokines also changed.ConclusionSpaceflight may affect physiological characteristics of tumor cells, and that, there was a negative correlation between the ratio of surviving cells and carrying time.