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Objective@#To study the efficacy, safety and long-term outcomes of integrated strategy of bortezomib-based induction regimens followed by autologous hematopoietic stem cell (ASCT) and maintenance therapy in Chinese multiple myeloma (MM) patients.@*Methods@#200 MM patients receiving integrated strategy of bortezomib--based induction regimens followed by ASCT and maintenance therapy were retrospectively and prospectively analyzed from December 1. 2006 to April 30. 2018.@*Results@#The complete remission rates (CR) and better than very good partial remission rates (VGPR) after induction therapy, transplantation and maintenance therapy were respectively 31% and 75.5%, 51.8% and 87.7%,73.6% and 93.4%. There was no difference between 4 cycles and more than 5 cycles induction chemotherapy. The negative rate of MRD detection by flow cytometry was 17.6% and 38.2% respectively after induction and 3 months after transplantation. The negative rate of MRD gradually increased during the maintenance therapy. The success rate of high dose CTX combined with G-CSF mobilization was 95.5% and transplantation related mortality (TRM) was zero. The median time to progress (TTP) was 75.3 months and the median overall survival (OS) was 99.5 months. TTP of patients obtaining CR and negative MRD after induction were longer that those of no CR and positive MRD. TTP and OS of patients receiving triple-drug induction and ASCT in early stage were longer than those of double-drug induction and ASCT in late stage. LDH≥240 U/L, high risk cytogenetics, ISS II+III stage and HBsAg positive were prognostic factors at diagnosis. However, only MRD and high risk cytogenetics were independent prognostic factors after transplantation and maintenance therapy. The clinical characteristics of patients of TTP ≥6 years were listed below: light-chain type M protein, ISS I stage, normal level of hemoglobin and platelet, normal LDH, HBsAg negative, chromosome 17p-negative, good response and sustained good response.@*Conclusions@#Integrated strategy of bortezomib-based induction regimens followed by ASCT and maintenance therapy can significantly improve the short-term and long-term efficacy. The prognostic factors of TTP in different disease stages were different. Response to treatment, especially MRD, played a more important role in prognostic factors.
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Objective To explore the clinical features of infection in multiple myeloma (MM)undergoing autologous hematopoietic stem cell transplantation (ASCT). Methods Thirty-seven patients with MM undergoing ASCT were retrospectively analyzed for type and time of infection, pathogen, and outcome. Results Fifty-nine cases of infectious complications occurred in 33 patients (89. 2% ) after ASCT, with 34 cases (57.6%) of bacterial infections in 30 patients, 15 cases (25.4%) of fungal infections in 12 patients, 4 cases (6. 8% ) of cytomegalovirus (CMV) infection, 3 cases (5. 1% ) of herpes zoster virus infection and 3 cases (5. 1% ) of HBV reactivation. The proportion of bacterial infection, fungal infection and virus infection were 62. 8%, 28.6% and 8. 6% respectively in the early stage after ASCT, and 50. 0%, 20. 8% and 29. 3% respectively in the median stage. Response to first-line antibiotic therapy was seen in 38 cases (64. 4% ). Infection-related mortality was 8. 1% (3 cases). Conclusions The incidence of infection in MM patients undergoing ASCT is high and they are susceptible to all pathogens. It is important to choose the right antifungal agents as quickly as possible to reduce infection-related mortality.
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<p><b>OBJECTIVE</b>To evaluate the mechanism and influence of thalidomide on interleukin-6 (IL-6), IL-6 receptor (IL-6R) and its transmitting chain in multiple myeloma patients.</p><p><b>METHODS</b>Serum level of IL-6, expression of IL-6R on myeloma cells and IL-6R beta mRNA in multiple myeloma patients were measured by enzyme linked immunosorbent assay (Elisa), flow cytometry and reverse transcription polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>Serum level of IL-6 in multiple myeloma patients was 564.8 +/- 319.4 ng/L, with a positive rate on the myeloma cells of 33.6% before oral 200 mg/d thalidomide. They were 560.3 +/- 414.8 ng/L and 31.8% on D14 after oral 200 mg/d thalidomide, which were not significantly different as compared with those before (P > 0.05). On D14, 28, 42, 56 and 84 after oral 400 mg/d thalidomide, the serum level of IL-6 in multiple myeloma patients were 516.7 +/- 131.9 ng/L, 426.7 +/- 180.4 ng/L, 387.9 +/- 187.4 ng/L, 350.1 +/- 85.5 ng/L and 212.3 +/- 92.5 mg/L, with positive rates on the myeloma cells of 28.5%, 24.3%, 21.3%, 12.6% and 10.1%, which were all lower than those before oral 200 mg/d thalidomide (P < 0.05 or P < 0.01). Ratios before and on D14 after oral 200 mg/d thalidomide were 7.8 and 6.9, with no statistical significance (P > 0.05). Ratios on D14, 28 after oral 400 mg/d thalidomide were 5.3 and 2.7, which were lower than those before oral 200 mg/d thalidomide (P < 0.01).</p><p><b>CONCLUSION</b>Reduction of serum level of IL-6 in multiple myeloma patients and decrease in IL-6R expression on the myeloma cells and IL-6R beta mRNA occur on D14 after oral 400 mg/d thalidomide. These changes become more obvious with time. The antitumor mechanism of thalidomide may be related to reduction of IL-6 serum level in multiple myeloma patients and decrease in IL-6R expression on the myeloma cells and IL-6R beta mRNA.</p>
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Angiogenesis Inhibitors , Pharmacokinetics , Pharmacology , Interleukin-6 , Blood , Genetics , Multiple Myeloma , Blood , Metabolism , RNA, Messenger , Metabolism , Receptors, Interleukin-6 , Metabolism , Thalidomide , Pharmacokinetics , PharmacologyABSTRACT
AIM: Through detecting bone marrow angiogenic mediators and inhibitors in aplastic anemia(AA) patients,the value of angionesis in AA pathogenesis was elucidated.METHODS: The patients were divided into severe AA group(SAA,8 patients),non severe AA group(NSAA,10 patients),and normal control group(7 persons),5 patients were observed before treating(group beginning) and getting improvement(group improving).The angiogenic mediators vascular endothelial growth factor(VEGF) and bFGF were detected by ELISA,angiogenic inhibitors IFN? and TSP were detected by ELISA and flow cytometry,respectively.RESULTS: The levels of VEGF were lower in SAA group and NSAA group than those in control group significantly(P
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AIM: To observe the cytotoxicity on myeloma cells mediated by anti-CD20 monoclonal antibody-mabthera, after heightening level of CD20 expression on myeloma cells membrane by ?-interferon. METHODS: 10 untreated(UT) and 10 relapsed or refractory(RR) MM patients'myeloma cells were cultured with human recombinant ?-interferon (hr?-IFN) at concentrations of (0-800)?10~3 U/L to heighten level of CD20 expression, then complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) on myeloma cells mediated by mabthera were studied through MTT methods. RESULTS: When CD20 expression of UT MM and RR MM patients' myeloma cells increased after treated by hr?-IFN, 12 mg/L and 16 mg/L mabthera mediated ADCC and CDC (against) myeloma cells in group UT patients and group RR patients, respectively. CONCLUSION: After heightened level of CD20 expression on myeloma cells membrane by hr?-IFN, mabthera mediated ADCC and CDC against myeloma cells in vitro.
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AIM: To study the effect of Bene Jones protein (BJP) from multiple myeloma(MM) patient and TGF-? 1 on cultured renal proximal tubular cell(PTC) proliferation. METHODS:[ 3H] TdR incorporation was used to study the effect of ?BJP and TGF-? 1 on cultured rat NRK.52E PTC proliferation,the expression of TGF-? 1 in the supernatant of PTC cultured with BJP was assessed with ELISA. RESULTS:① [ 3H] TdR incorporation of PTC was inhibited by BJP in a dose-dependent manner,when co-cultured with 100-800 ?mol/L BJP and 2.0 ?g/L TGF-? 1, the [ 3H] TdR incorporation was lower than that of BJP alone, especially when BJP≥400 ?mol/L; ②The expression of TGF-? 1 in the supernatant of PTC cultured with BJP was increased ,especially when BJP≥400 ?mol/L( P