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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.
Subject(s)
Humans , Antineoplastic Combined Chemotherapy Protocols , Bortezomib/therapeutic use , Follow-Up Studies , Hematopoietic Stem Cell Transplantation , Induction Chemotherapy , Multiple Myeloma/therapy , Retrospective Studies , Stem Cell Transplantation , Transplantation, Autologous , Treatment OutcomeABSTRACT
Defective dendritic cell (DC) functions have been implicated in ITP. The purpose of this study was to investigate the distribution and activation of dendritic cells in immune thrombocytopenia (ITP) patients. ITP patients were divided into 3 groups: the newly diagnosed, refractory and effective treatment group. The distributions of plasmacytoid dendritic cells (pDC) and myeloid dendritic cells (mDC) in peripheral blood, bone marrow and spleen were detected with flow cytometry. The expression level of CD80 and CD86 on surface of pDC and mDC was also detected with flow cytometry. The results indicated that the percentage of mDC was higher than that of pDC in all sites of all groups. The percentage of mDC and pDC in all site of refractory group was higher than that in newly diagnosed and effective groups, but the percentage of mDC in spleen of refractory group was obviously higher than that in other sites. The percentage of pDC was no significant different in all groups. The expression level of CD86 in all groups was higher than that of CD80, the expression level of CD80 was lower in mDC and pDC of all groups, but there was no obvious difference in all sites. The CD86 expression in all site of refractory group was higher than that in newly diagnosed and effective treatment groups, while the CD86 expression of mDC in spleen of newly diagnosed group obviously higher than that in other sites. It is concluded that the distribution abnormality of mDC and pDC exists in ITP patients, the mDC are more accumulated in spleen, and differentiation of mDC to maturity is more obvious in spleen, spleen-derived mDC significantly express CD86, spleen-derived mDC may play an important role in the pathogenesis of ITP.
Subject(s)
Adult , Female , Humans , Male , B7-1 Antigen , Metabolism , B7-2 Antigen , Metabolism , Dendritic Cells , Cell Biology , Allergy and Immunology , Purpura, Thrombocytopenic, Idiopathic , Allergy and Immunology , Spleen , Cell BiologyABSTRACT
This study was purposed to investigate the B cell-activating factor belonging to the TNF family (BAFF) and a proliferation-inducing ligand (APRIL) levels in bone marrow, and the BAFF receptor expression level on B cells in multiple myeloma (MM) patients, in order to explore the characteristics of B cells in bone marrow of MM patients. MM patients were studied before treatment (newly diagnosed group, 19 patients) and after treatment with improvement (stable group, 17 patients), 10 non-hematologic patients were selected as control (control group). The BAFF receptors (BAFF-R) and transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) on B cell (CD19(+)), naive B cell (CD19(+)IgD(+)) and memory B cell (CD19(+)CD27(+)) of bone marrow in all groups were detected by flow cytometry. The BAFF, APRIL level in bone marrow supernatant were tested with ELISA. The results showed that the BAFF-R expression level on CD19(+) cells in newly diagnosed group were higher than that in stable group and control group; there was no significant difference between the BAFF-R expression level on CD19(+)IgD(+) cells in newly diagnosed group and stable group, but BAFF-R expression level on CD19(+)IgD(+) cells in newly diagnosed group was higher than that in control group; the BAFF-R expression level on CD19(+)CD27(+) cells in newly group was higher than that in stable group and control group; there was no significant difference between the BAFF-R expression level on CD19(+) cells, CD19(+)IgD(+) cells or CD19(+)CD27(+) cells in stable group and control group. There was no significant difference among the TACI expression level on CD19(+) cells, CD19(+)IgD(+) cells or CD19(+)CD27(+) cells in newly diagnosed group, stable group and control group. The bone marrow supernatant BAFF level in newly diagnosed group was higher than that in stable group and control group, but there was no significant difference between stable group and control group. There was no significant difference among the bone marrow TACI levels in newly diagnosed group, stable group and control group. It is concluded that both the bone marrow BAFF level and the BAFF-R expression level on CD19(+) cell, CD19(+)IgD(+) cells and CD19(+)CD27(+) cells in MM patients increase, which may help to stimulate B cells, thereby may relate with to MM pathogenesis.
Subject(s)
Humans , Middle Aged , B-Cell Activating Factor , Metabolism , B-Cell Activation Factor Receptor , Metabolism , Bone Marrow , Metabolism , Multiple Myeloma , Metabolism , PathologyABSTRACT
Objective To investigate the dynamic change and associated risk factors of HIV sero-conversion rate in Beijing.Methods 809 sero-negative men who have sex with men (MSM) were recruited in the cohort from August to December in 2009.HIV sero-antibody,medicinal examination and behavior questionnaire interview were carried out every six months.Results 962 MSM with overall baseline prevalence of HIV infection as 6.34% (61/962) together with 809 seronegative MSM,were enrolled in the cohort.Of the 809 sero-negative participants,95.1% (769/809),85.5% ( 692/809 ) and 71.0% ( 574/809 ) of them were retained in the 6-month,12-month and 18- month follow-up visits,with 19,29 and 17 of them became HIV sero-conversion at 6-month,12-month,and 18-month follow-up visits and the HIV incidence rates appeared to be 5.47,12.37 and 6.86 per 100 person-years respectively.The HIV incidence was 7.59 per 100 person-years in the 18 months follow-up visit.Factors including:younger than 25-years old (HR =2.32,95%CI:1.39-3.87),having more than 8 MSM partners (HR=2.50,95%CI:1.49-4.20),less than RMB 2000 Yuan every month income (HR=1.76,95%CI:1.06-2.95 ),having more than 4 homosexual partners in the last six months (HR=3.50,95% CI:2.11 -5.81 ),showing phimosis and redundant prepuce (HR=2.47,95% CI:1.50-4.07 ) as well as positive syphilis test (HR=2.62,95%CI:1.53-4.49) etc.,were significantly associated with HIV incidence.Conclusion High HIV incidence was shown among MSM in Beijing and had spread fast in this population,calling for more favorable prevention measures to be taken.
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This study was aimed to analyze the correlation of CD19 positive cell counts in bone marrow of multiple myeloma(MM) patients with therapeutic efficacy and investigate the characteristics of CD19 cell change in MM bone marrow. The CD19(+) and CD38(++)CD45(-), CD38(++)CD45(-)CD56(+) cells in bone marrow of 63 MM patients were detected by flow cytometry. The difference of CD19(+), CD38(++)CD45(-), CD38(++)CD45(-)CD56(+) cell counts at different stages and types, as well as their relation with results of 4 course of VADM or VD chemotherapy were analyzed. The results showed that in 63 MM patients, CD19(+) cell ratio at stage II were higher than those at stage III; CD38(++)CD45(-)CD56(+) cell ratio at stage II were lower than those at stage III; CD19(+) cell ratio in type IgA were higher than those in type IgD; the CD38(++)CD45(-), CD38(++)CD45(-)CD56(+) cell counts in type IgA were obviously lower than those in type IgG, IgD and light chain which showed a negative correlation between cell counts of CD19(+) against CD38(++)CD45(-), CD38(++)CD45(-)CD56(+). CD19(+) cell counts in effective treatment group of all 43 patients and the effective treatment group with VD were both higher than those in the ineffective treatment group; CD38(++)CD45(-) cell counts in effective treatment group with VD was obviously lower than those in ineffective treatment group, and CD38(++)CD45(-), CD38(++)CD45(-)CD56(+) in effective treatment group of all 43 patients were lower than those in ineffective treatment group. It is concluded that CD19(+) cell counts in bone marrow may be related to disease status and development stage of MM, which may be useful to predict treatment efficacy and prognosis.
Subject(s)
Humans , Middle Aged , Antigens, CD19 , Metabolism , Bone Marrow Cells , Cell Biology , Metabolism , Multiple Myeloma , Diagnosis , Therapeutics , Treatment OutcomeABSTRACT
<p><b>OBJECTIVE</b>To study the incidence and risk factors of HIV and syphilis seroconversion among men who have sex with men (MSM) in Beijing.</p><p><b>METHODS</b>A total of 550 MSM were recruited on the basis of community and followed up after 6 and 12 months in Beijing. Each subject was investigated by only one investigator at one time to collect information on demographics and behaviors. Blood samples were collected to test HIV and syphilis seroconversion. ELISA was used for screening test, west blotting (WB) and Particle agglutination were used for confirmatory test.</p><p><b>RESULTS</b>A total of 550 MSM investigated, among which 4.5% (25/550) were HIV-positive and 29.3% (161/550) were syphilis-positive. For 525 HIV-negative MSM, 87.0% (457/525) retained during the 12-month investigation. Seroincidence for HIV and syphilis were 3.37/100 person-years (95%CI = 1.66 - 5.08) and 9.32/100 person-years (95%CI = 5.87 - 12.77) respectively. HIV seroconversions for those who performed and did not perform rectal douching after homosexual anal intercourse in the past 3 months were 7.11/100 and 0.76/100 person-years respectively. Multivariate Cox regression analysis revealed that rectal douching after homosexual anal intercourse in the past 3 months (HR = 9.23, 95%CI = 2.08 - 40.88) was significantly associated with HIV seroconversion. Syphilis seroconversions for those who met male sex partners in parks, public washrooms or bathhouses in the past 3 months were 41.77/100 and 7.97/100 person-years respectively. Syphilis seroconversions for those who performed and did not perform rectal douching after homosexual anal intercourse in the past 3 months were 16.17/100 and 4.92/100 person-years respectively. In the past 3 months, meeting male sex partners in parks, public washrooms or bathhouses (HR = 4.67, 95%CI = 1.77 - 12.34) and performing rectal douching after homosexual anal intercourse (HR = 3.09, 95%CI = 1.40 - 6.83) were significantly associated with syphilis seroconversion.</p><p><b>CONCLUSION</b>The seroconversions of HIV and syphilis during the follow-up visits in this MSM cohort study in Beijing were very serious, and that the associated factors for seroconversions were rectal douching after homosexual anal intercourse and meeting male sex partners in parks, public washrooms or bathhouses.</p>
Subject(s)
Adolescent , Adult , Humans , Male , Young Adult , Antibodies, Bacterial , Blood , China , Epidemiology , HIV , Allergy and Immunology , HIV Antibodies , Blood , HIV Infections , Blood , Epidemiology , HIV Seropositivity , Blood , Epidemiology , Homosexuality, Male , Incidence , Risk Factors , Sexual Behavior , Syphilis , Blood , Epidemiology , Treponema pallidum , Allergy and ImmunologyABSTRACT
Objective To study the prevalence and risk factors of human immunodeficiency virus (HIV) among men who have sex with men (MSM) in Beijing. Methods A sample of 550 MSM was recruited between March and June in 2008 in Beijing. Interviewer-administered interviews were conducted to collect information on demographics and behaviors. Blood samples were collected to test for HIV,syphilis,HBsAg and HCV infections. Chi-square test and logistic regression model were used to identify risk factors associated with HIV infection. Results Of the 550 eligible MSM surveyed,HIV prevalence appeared to be 4.5% (25/550). Data from multivariate logistic regression analysis demonstrated that factors as reporting unprotected anal intercourse with causal male sexual partners in the last month (X~2=11.381,P=0.001),rectal douching after homosexual anal intercourse in the past three months (X~2=5.326,P=0.021),feeling sad in the last month (X~2=8.809,P=0.003) were significantly associated with HIV infection. Conclusion Health education on safer sex behavior and mental health care should be taken to hinder the speed of HIV transmission among MSM.
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<p><b>BACKGROUND AND OBJECTIVE</b>Vascular endothelial growth factor (VEGF) is the most important angiogenic factor of multiple myeloma (MM). This study was to investigate the effect of transfection of human soluble vascular endothelial growth factor receptor-1 (sFlt-1) gene on the proliferation of human MM cell line RPMI8226.</p><p><b>METHODS</b>The recombinant plasmid pcDNA3-sFlt-1 was constructed and transfected into RPMI8226 cells. The expression of sFlt-1 was identified by reverse transcription-polymerase chain reaction (RT-PCR) and ELISA. The effects of sFlt-1 protein on the proliferation and VEGF expression of RPMI8226 cells were investigated by MTT assay and ELISA, respectively.</p><p><b>RESULTS</b>The recombinant plasmid pcDNA3-sFlt-1 was successfully transfected into RPMI8226 cells. sFlt-1 protein expression was identified by ELISA, which inhibited the proliferation of RPMI8226 cells and reduced VEGF concentration in the culture supernatant.</p><p><b>CONCLUSION</b>RPMI8226 cells can express sFlt-1 protein with high biological activity when transfected with the sFlt-1 gene, which inhibits the proliferation of RPMI8226 cells.</p>
Subject(s)
Humans , Cell Line, Tumor , Cell Proliferation , Enzyme-Linked Immunosorbent Assay , Gene Expression Regulation, Neoplastic , Multiple Myeloma , Genetics , Metabolism , Pathology , Plasmids , Recombinant Proteins , Genetics , Metabolism , Reverse Transcriptase Polymerase Chain Reaction , Transfection , Vascular Endothelial Growth Factor A , Metabolism , Vascular Endothelial Growth Factor Receptor-1 , Genetics , Metabolism , PhysiologyABSTRACT
<p><b>OBJECTIVE</b>To explore the characteristics of B cell-activating factor (BAFF) secreted by peripheral blood monocyte-derived dendritic cell (MoDC) in chronic idiopathic thrombocytopenic purpura (cITP) and the function of MoDC on B cell proliferation.</p><p><b>METHODS</b>Ten cITP patients were studied dynamically before and after treatment. The BAFF levels in serum and the supernatant of LPS stimulated MoDC were tested with ELISA. The BAFF gene expression in LPS stimulated MoDC was tested with RQ-PCR, the B cell proliferation co-cultured with the supernatant of LPS stimulated MoDC for 5 days was tested with flow cytometry for CFSE and (3)H thymidine incorporation.</p><p><b>RESULTS</b>The BAFF level in serum (serum BAFF) \[(2461 ± 483) ng/L\], and supernatant of LPS stimulated MoDC (supernatant BAFF) \[(1113 ± 113) ng/L\] and BAFF mRNA in LPS stimulated MoDC (BAFF mRNA) (1.70 ± 0.23) before treatment were higher than that after treatment \[(621 ± 53) ng/L, (490 ± 49) ng/L and 0.37 ± 0.12\] and normal group \[(742 ± 77) ng/L, (582 ± 63) ng/L and 0.52 ± 0.08\]. There was a positive correlation among serum BAFF, supernatant BAFF and BAFF mRNA, and a negative correlation among serum BAFF, supernatant BAFF and BAFF mRNA and blood platelet count (BPC) in all ITP patients. The supernatant of LPS-stimulated MoDC from untreated patients enhanced B cell proliferation as compared with the supernatant of LPS-stimulated MoDC from treated patients and normal group.</p><p><b>CONCLUSION</b>BAFF might contribute to disease development in cITP. MoDC may directly increase B cell proliferation by secreting BAFF without T cell help, playing an important role in the antibody production in cITP.</p>