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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 compare the efficacy, response and survival between high-dose melphalan (HDM) and cyclophosphamide+ etoposide+ busulfan (CVB) as the conditioning regimen in autologous stem cell transplantation (ASCT) for newly diagnosed multiple myeloma (NDMM) .@*Methods@#Retrospectively enrolled 123 consecutive NDMM patients who had received PAD induction with subsequent ASCT from Jan 2011 to Aug 2017. The CVB group and HDM group had 82 and 41 patients respectively.@*Results@#①No differences existed between these 2 groups in non-hematological side effects. ②Patients of CVB group had faster neutrophil and platelet engraftment time, with the median neutrophil engraftment time of 10 (9-35) day vs 11 (9-12) day for patients of HDM group (z=-3.433, P=0.001) , and with median platelet engraftment time of 11 (7-55) day vs 13 (10-35) day for patients of HDM group (z=-3.506, P<0.001) . CVB group entered neutropenia and severe thrombocytopenia more earlier than the HDM group, resulting similar neutropenia duration and severe thrombocytopenia duration between the CVB group and HDM group. However, patients of CVB group had significantly longer fever persistent time and antibiotic administration time. ③The response rate was significantly lower in patients of CVB group vs. patients of HDM group (9/46 vs 14/28, P=0.021) . Further, the minimal residual disease (MRD) negative rate at 3rd month post-transplantation seemed to be lower in CVB group than that in HDM group (31.7%vs 48.8%, P=0.065) . ④Both the univariate and multivariate analysis showed that HDM and CVB groups had similar duration to progression (TTP) (P=0.619) and overall survival (OS) (P=0.295) .@*Conclusion@#HDM conditioning regimen is superior to CVB regimen in hematological side effects, tumor burden reduction and administration convenience. However, these two regimen had similar TTP and OS in MM patients receiving ASCT.
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Objective To investigate the efficacy and safety of bortezomib-based induction regimen followed by autologous hematopoietic stem cell transplantation (ASCT) in pationts with multiple myeloma (MM). Methods A retrospective analysis was performed upon clinical data of 62 MM patients who received bortezomib-based induction regimen followed by ASCT from June 2006 to June 2011.All patients were followed up to September 30,2011.Results Overall response rate [ complete remission (CR) + near complete remission (nCR) + partial remission (PR) ],≥ nCR rate (CR/nCR) and CR rate of postinduction with bortezomib-based regimen were 88.7％,66.1％ and 24.2％,respectively.After ASCT,CR rate and CR/nCR rate were increased to 50.0％ and 82.3％,respectively,with significant differences (P =0.003 and P =0.032).The median time of neutrophil and platelet engraftment was 12.0 (9-43) days and 13.5 (0-120) days,respectively. Significances were found in neutrophil and platelet engraftment between MM patients with and without prior exposure to alkylating agents. Furthermore,engraftment of neutrophil and platelet in patients receiving peripheral blood stem cell transplantation were faster than those receiving bone marrow transplantation.No unexpected side effects occurred.The median time of follow-up was 26.5 (7-61) months.The median overall survival (OS) was not reached and the median progression-free survival (PFS) was 30 months.There were significant differences in OS and PFS between patients obtaining CR/nCR and those with ≤ PR before ASCT.Conclusions Bortezomib-based induction regimen can improve the efficacy of ASCT in MM patients.The side effects are tolerant.Higher response quality before ASCT can translate to high rates of OS and PFS following high-dose therapy and stem cell transplantation.
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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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AIM: To observe the expression of β-catenin in patients with chronic myeloid leukemia (CML) at different disease phases, and to analyze the relationship between BCR-ABL and cytogenetic response to imatinib mesylate. METHODS: RT-PCR and Western blotting were used to detect β-catenin mRNA and protein expression in bone marrow mononuclear cells (BMMNCs) from 99 patients with CML. The association with BCR-ABL and BCR-ABL fusion was determined by FISH in 94 patients after one year treatment with imatinib mesylate, and the relationship between β-catenin and cytogenetic response to imatinib mesylate was analyzed. RESULTS: The expression of β-catenin was increased significantly in patients with blast crisis and accelerated phase (P<0.01), while the expression of β-catenin between normal person and chronic phase of CML patients was not statistically different (P>0.05). No significant relation between β-catenin and BCR-ABL expression (r=0.314, P>0.05) was observed. The expression of β-catenin was increased significantly in the patients who did not reach main cytogenetic remission (P<0.01). CONCLUSION: The patients in progression phases of CML over-express β-catenin. The expression of β-catenin is not significantly related to BCR-ABL expression, but related to the therapeutic response of imatinib. Beta-catenin may be involved in the mechanism of CML progression and could be used as a new therapeutic target.
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Objective To investigate the effect of bortezomib on the proliferation and apoptosis in leukemia cell line NB_4-R2 in vitro and provide some new evidences for the treatment of acute promyelocytic leukemia APL with ATRA-resistant using bortezomib. Methods NB_4-R2 cells were incubated with bortezomib at different does for 48 h. The proliferation capacity was measured by MTT assay, the morphology of cell apoptosis observed with Hoechst33342 staining by fluorescence microscopy and the percentage of apoptosis calculated by flow cytometry. The expression of apoptosis protein of cleaved (poly ADP-ribose polymerase, PARP) and Caspase-3 were determined by Western blotting. Results The proliferation of NB_4-R2 cells were obviously inhibited by bortezomib in vivo and the role of inhibition was a does-dependant manner within the scope of the bortezomib concentration from 1-5 μg /L.The incidence of inhibition was up to 74.9 % at the bortezomib concentration of 5 μg/L. Within this scope of the bortezomib concentration mentioned above, the role of inhibition of proliferation of NB_4-R2 cells mainly showed an increase of the late apoptosis, and the percentage of apoptosis was up to 78.9 %. In the meaning time, the expressions of the apoptotic protein of cleaved PARP and Caspase-3 were up-regulated in NB_4-R2 cells after treated with bortezomib by Western blotting assay. Conclusion Bortezomib can inhibit the proliferation of NB_4-R2 cells in vivo by inducing cell apoptosis.
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Objective To explore the influencing factors and possible mechanism of osteonecrosis of the femoral head(ONFH)in patients with leukemia after allogeneic hematopoietic stem cell transplantation (Allo-HSCT).Methods One hundred and two patients with leukemia who received Allo-HSCT between January 2003 and October 2007 were evaluated for ONFH and graft-versus-host disease(GvHD)within 2years after transplantation,and the dosage of methylprednisolone(MP)in every patient from the first diagnosis of leukemia to 2 years after Allo-HSCT was calculated.For patients who suffered acute GvHD(aGvHD) and chronic GvHD(cGvHD),the serum leveh of soluble ligand of receptor activator of nuclear factor kappa B (sRANKL)which was index for differentiation of osteoclast(OC),tartrate-resistant acid phosphatase-5b(TRAP-5b)and C-terminal telopeptide of collagen Ⅰ(CTP-Ⅰ)which both were indexes for metabolism of OC were detected by enzyme-linked immunosorbent assay in different stages of MP dosage.According to these results.possible factors for ONFH after Allo-HSCT were analyzed.Results Seven in 102 patients after Allo-HSCT had experienced ONFH within 2 years,the incidence was 6.9%(7/102),which was not related to age,gender,types of leukemia and donor.ONFH mainly developed in patients with aGvHD and cGvHD,and the incidence could be achieved to 21.9%(7/32)which Was much higher than that in patients with no GvHD,merely aGvHD or merely cGvHD(P<0.05).In patients with aGvHD and cGvHD,the average dosage of MP in ONFH(+)was(232.7±28.6)mg/kg which was extremely higher than that in ONFH(-)(115.1±16.9)mg/kg(P<0.05).The serum levels of sRANKL,TRAP-5b and CTP-Ⅰ were also higher when ONFH happened than ahead of pretreatment and 28 days after transplantation(-)(P<0.05),and they were closely related to the dosage of MP(correlation coefficient was 0.597,0.664 and 0.682 respectively,P<0.05).Conclusions After Allo-HSCT,ONFH is related to the dosage of MP in treatment of GvHD.MP may be responsible for enhancement of OC differentiation and metabolism in leukemia patients,and ultimately induced the onset of ONFH.
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Objective To compare the clinical efficacy and complications of allogeneic peripheral blood stern cell transplantation (Allo-PBSCT) and immunosuppressive therapy (IST) for severe aplastic anemia(SAA). Methods Twenty-five patients with SAA underwent allogeneic HLA-matched sibling donor PBSCT(n = 12) and IST (n = 13). PBSCT group received conditioning regimen of cyclophosphamido(Cy) in combination with antithymocyte globulin(ATG). IST group received ATG followed by cyclosporine A (CsA).The short-term and long-term effects and complications were investigated. Results The mean time of recovery in the absolute neutrophil count (ANC), platelet and hemoglobin (Hb) in PBSCT group [(13.5±2.3), (23.5±4.1), (82.7±6.1)d, respectively]was shorter than those in IST group [(32.6±3.5), (73.8±6.2), (296.4±12.5)d, respectively]and there were statistical differences between two groups(P<0.05). But the one-year treatment effect between two groups showed no difference (P>0.05). There were no statistical differences in 3-year survival and overall survival rate between two groups (P>0.05). However, statistical difference was observed in overall relapse rate (P<0.05). The common complication in two groups was virus infection including cytomegalovirus (CMV) and varicella zoster virus (VZV), but there was no statistical difference in the incidence of virus infection between them (P>0.05). Conclusions Both allo-PBSCT and IST are effective methods for treating patients with SAA. PBSCT is considered preferentially in clinic, because of its advantages in faster hematopoietic engraftment, lower relapse rate and no increased complication.
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Objective To investigate the influence of the PBSC collection yield by choosing the differ-era venous accesses in the healthy donors. Methods 118 healthy PBSC donors performing PBSC collection between January 2000 and December 2007 in our hospital were divided into four groups according to the differ-ent venous accesses. The PBSC collection yield of four groups,including mononuclear cells (MNC) count and CD34+ cells count were observed. Results In the ulnar V-ulnar V group,MNC (5.31±2.29)×108/kg,CD34+ cells (4.78±2.06)×106/kg;ulnar V- antecubital V group,MNC(5.11±2.34)×108/kg,CD34+cells(4.34±1.99)×106/kg;antecubital V- antecubital V group,MNC (5.61±1.73)±×108/kg,CD34+cells (4.60±1.42)×106/kg;ulnar V- radial V group,MNC(4.60±×1.70)×108/kg,CD34+cells (4.05±1.50)×106/kg.There was no statistical differ-ence of the PBSC collection yield between four groups (P>0.05). Conclusions Different venous accesses don't affect the PBSC collection yield in the PBSC healthy donors.
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Objective To compare effects and toxicities of DVd and VAdM regimen for newly diagnosed multiple myeloma.nethods 17 newly diagnosed active multiple myeloma received DVd treatment,dexamethasone(20 mg/d)on days 1～4 as an intravenous infusion.16 newly diagnosed active multiple myeloma on days 1～4 plus melphalan(12 mg/d)as an intravenous infusion.Results Objective response rates(DVd,76.5%;VAd,81.3%,P=0.737)were similar between the two treatment groups.In the DVd group,the mean time to max response was shorter than the VAdM group[(3.2±1.7)months vs.(4.6±1.0)months,P=0.039].DVd was associated with low Grade 3/4 neutropenia(23.5% vs.68.8%,P=0.015),less use of G-CSF(11.8% vs.62.5%,P=0.004),less use antibiotic(11.8% vs.37.5%,P=0.118),lower incidence of hospitalization for adverse events(37.5% vs.17.6%,P=0.259),but more hand-foot syndrome.Coilcinsion The DVd regimen demonstrated similar efficacy compared with VAdM,while with less toxicity and supportive care,which might be used as a modified VAd regimen for newly diagnosed myeloma.
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0.05).Conclusion Performing leukapheresis and plateletpheresis sequencially with a single Apheresis Kit is a safe,effective,practicable and economic method in the treatment of chronic myeloid leukemia with leukocytosis and thrombocytosis.It can drop the medical expanse markedly.
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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>
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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
0.05),but both groups reached a better result when compared with the auto-HSCT group(P
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Objective To explore the total treatment effect,layered diagnostic treatment effect,the relationship between effect and site of infection and common side effects of commonly used antifungal agents such as itraconazole,Voriconazole,caspofungin and amphotericin B liposome in invasive fungal infection with hematologic malignancies.Methods The clinical data of 117 cases of patients with hematologic malignancies combining with invasive fungal infection hospitalized in our department from Jan,2005 to Aug,2008 were retrospectively analyzed.Results The total effect rates of itraconazole,Voriconazole,caspofungin and amphotericin B liposome were 69.0%(40/58),77.4%(24/31),64.7%(11/17)and 63.6%(7/11)respectivley(P=0.726).In patients with pulmonary infection,the effect rates of the agents were 63.0%(17/27),85.7%(12/14),50.0%(4/8)and 62.5%(5/8)respectively(P=0.283),which itraconazole group was higher than that of the other agents.The effect rates of the 4 groups have similar rates in patients with liver and spleen candidiasis,fungemia and infections with unknown origin.The rates of 6 weeks survival were 86.2%,87.1%,70.6% and 72.7% respectively.The common side effects of itraconazole and Voriconazole were mainly gastrointestinal reaction and mild hypokalemia.There were few patients showed gastrointestinal reaction(12.1%) and hypokalemia(20.7%)in the former.Some individual showed visual abnormity(9.7%)and external vertebral body symptoms(6.4%).caspofungin showed mild toxic and side effects,which was only gastrointestinal reaction(15.4%),while they were common in amphotericin B liposome group,which were Chill and fever(81.8%),hypokalemia(100%),gastrointestinal reaction(18.2%)and liver damage(9.1%).Conclusion The total effect,layered diagnostic effect and 6 weeks survival rates were similar in itraconazole,Voriconazole,caspofungin and amphotericin B liposome in patients with hematologic malignancies combining with invasive fungal infection.
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0.05).We did not find any difference of the expression of fibronectin,laminin and type IV collagen in them.Expression of ICAM and VCAM were(56.4?14.8)% and(55.6?12.2)%,respectively,obviously higher than those in control group(P
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Purpose:To study the efficacy and toxicity of VIDM regimen (vincristine,idarubicin,dexamethasone and melphalan) for refractory or relapsed multiple myeloma(MM).Methods:45 refractory or relapsed MM patients were randomized into two groups: VIDM group(treatment group) had 22 patients treated with VIDM regimen, VAD group(control group) had 23 patients with VAD regimen.Results:The effective rate with VIDM regimen (59.1%) was significantly higher than that of VAD regimen (26.1%) (P
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AIM: To re-identify the special motif regulating osteoclast(OC)differentiation in receptor activator of nuclear factor kappa B(RANK)to provide evidences for studying the mechanism of OC differentiation.METHODS: Eight amino acids were mutated(from DIIVVYVS into ELLAAFAA)in the fragment between the 533th and the 540th amino acids in RANK cytoplasmic domain.Eight mutant TNFR1/RANK chimeras,each consists of TNFR1(tumor necrosis factor receptor 1)extracellular domain linked to transmembrane domain and cytoplasmic domain of RANK with one amino acid mutated in cytoplasmic domain was constructed by point mutation method.After the eight mutant chimeras were finished,they were packed with plat E cell line to produce the retrovirus expressing mutant TNFR1/RANK.The bone marrow macrophages(BMMs),isolated from TNFR1/R2 double knockout mice,were infected with retrovirus derived from different mutants and infected BMMs which did not differentiated into OCs were inspected after stimulated by TNF-? and M-CSF.The fragment consisted of different amino acids in TNFR1/RANK chimeras,which couldn't induce OC formation after mutated,may be the special motif regulating OC differentiation.RESULTS: We found that all BMMs transfected by TNFR1/RANK-533,TNFR1/RANK-539 or TNFR1/RANK-540 differentiated into OCs,indicating that none of amino acids D533,V539 or S540 had an effect on OC differentiation.A fewer of BMMs transfected by TNFR1/RANK-534 differentiated into OCs,indicating that I534 had a partial effect on OC formation.Most importantly,BMMs transfected TNFR1/RANK-535,TNFR1/RANK-536,TNFR1/RANK-537 or TNFR1/RANK-538 did not differentiated into OCs,indicating each of amino acids I535,V536,V537 and Y538 played a pivotal role in OC differentiation.CONCLUSION: The amino acid fragment consists of I534,I535,V536,V537 and Y538 may be the special motif regulating OC differentiation in RANK.