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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 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 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 analyze the clinical pathology features of light-chain amyloidosis associated renal disease,and investigate the survival influential factors. Method From January 1998 to March 2009,25 patients with light-chain amyloidosis associated renal disease were reviewed and followed up.Results Of the 25 patients with light-chain amyloidosis associated renal disease,median age was 57(37-69) years old and lamda light-chain predominated (88% ,22/25). Heavy proteinuria and nephrotic syndrome with peripheral edema were typical clinical presentations. Renal biopsy showed that amyloid deposition of light-chain amyloidosis associated renal disease involved the glomeruh mostly, with mesangial area widening. Median survival of all patients was 24.4 months after diagnosis. The estimated 1,2,3 year survival rate was (65 ± 10 )%, (46 ± 12 )% and (15 ± 12 )% respectively. There was significant difference in median survival between the two groups (24.7 months in the group of 14 patients with isolated kidney affected,16.4 months in the group of 11 patients with kidney and other organs involved,P = 0.03). By univariate analysis, kidney associated with other organs amyloidosis and renal dysfunction were relevant to prognosis (P ＜ 0.05) and heart involvement was probably relevant (P = 0.06),whereas sex,age,plasma cell ratio,serum albumin level and hemoglobin level had no relation(P＞ 0.05 ). Multivariate analysis revealed that renal dysfunction at the time of diagnosis was a significant and independent prognostic factor for survival (P ＜0.05). Conclusions Renal dysfunction at the time of diagnosis is the best predictor of survival. The presence of amyloidosis in organs other than the kidney, such as advanced cardiac amyloidosis, predicts a poor survival.
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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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0.05),but both groups reached a better result when compared with the auto-HSCT group(P
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AIM: To determine the expression of membrane-bound B lymphocyte stimulator((BLyS)) and its mRNA in peripheral blood mononuclear cells(PBMCs) from individuals with systemic lupus erythematosus(SLE),and to investigate the effect of dexamethasone on(BLyS) expression.METHODS: PBMCs were obtained from 25 individuals with SLE(mean age of 31.40?14.23) and 20 female healthy volunteers(mean age of 28.20?10.36).They were randomized into dexamethasone((1 ?mol/L)) group and media group.PBMCs were gathered at 0,6,12 and 24 h for(BLyS) mRNA assessment using reverse transcription-PCR(RT-PCR).PBMCs were also collected at 72 h for membrane-bound(BLyS) protein detection using flow cytometry(FACS) and direct immunofluorescence.RESULTS:(1) The expression of(BLyS) mRNA and membrane-bound protein were significantly higher in PBMCs from individuals with SLE than that in PBMCs from healthy controls(0.40?0.18 vs 0.27?0.20,P
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Objective To investigate the telomerase activity and abnormality of p16 gene in liver metastatic tumors of colorectal carcinoma. Methods Telomerase activity was detected by a non isotopic PCR based TRAP assay (Telomeric repeat amplification protocol) and the homozygous deletions of p16 gene was detected by a semiquantitative multiple PCR in tissue samples from 24 liver metastases of colorectal carcinoma. Results Telomerase activity were observed in 19 (79 2%) out of the 24 colorectal carcinoma patients. There was no correlation hetween the telomerase activity, the number of metastasis, differentiation, liver fibrosis and HBsAg status of the patients. Homozygous deletions of p16 gene were found in 9 out of 24 (37 5%) patients, and homozygous deletions of p16 gene was significantly correlated with telomerase activity.Conclusion The abnormality in telomerase activity and homozygous deletions of p16 gene may be important for elucidating in liver metastases of colorectal carcinoma.
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Objective To explore the clinical characteristics of adrenoleukodystrophy (ALD). Methods The clinical date of 14 ALD patients were analyzed retrospectively. Results The 14 ALD patients were boys,the symptoms occurred slowly from 1 to 13 years old. The clinical manifestations of all the ALD patients were mainly mental retardation and disturbances of movement of extremities,9 cases had visual disorders,6 cases had auditory disorders and 13 cases had dysarthria,5 cases had seizure and 6 cases had increased skin pigmentation. The level of plasma very long chain fatty acids (VLCFA) in 5 csaes were increased at some degree.The brain CT from 2 cases and MRI from 12 cases showed butterfly-like focus in periventricle areas in the white matter bilaterally. Lace-like high intensity lesions were observed in 3 cases. Conclusion The clinical features of ALD are progressive dysnoesia,limbs dyskinesia,hypropsia,hearing loss etc,dysfunction of adrenal cortex,the level of plasma VLCFA increased,and with characteristic changes of skull imageological.
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Objective To study the direct effect of parathyroid hormone(PTH) on osteoclasts (OCs) differentiation and bone resorption in vitro and to explore the relationship between PTH and expression of RANKL (ligand of receptor activator of nuclear factor kappa B)gene and OPG (osteoprotegerin) gene in osteoblasts (OBs) in order to provide some theoretic evidence for understanding the pathogenesis of high-transferred renal osteodyslrophy (ROD). Methods PTH was directly used to induce OCs differentiation from whole bone marrow of C3h mouse by using OCs formation assay and then inspected the bone resorption of these OCs in vitro by using pits assay. Multiple RT-PCR assay was used to examine the expression of RANKL-mRNA and OPG-mRNA in different PTH concentrations and different treating times by PTH. Results (1) PTH in vitro could induce OCs formation form whole bone marrow of wild-type C3h mice.In a certain concentration scope, as the concentration of PTH increased, the number of differentiated OCs and the degree of bone destruction of OCs increased. (2) Expression of RANKL-mRNA and OPG-mRNA was in dose-dependent and time-dependent manner within a certain range of concentration and time. Conclusion PTH in vitro mediates OCs differentiation and bone resorption probably through the up-regulated expression of RANKL-mRNA and OPG-mRNA.
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AIM: To investigate the possibility of simultaneously ex vivo generating cytomegalovirus (CMV) pp65 and Epstein - Barr virus (EBV) - specific cytotoxic T lymphocytes (CTL) from human umbilical cord blood (CB). METHODS: Mononuclear cell derived from CB (CBMC) was used to construct EBV - transformed B-lym- phoblastoid cell lines (BLCL). Then BLCL were transduced with a recombinant retrovirus encoding pp65, the immunodominant CMV polypeptide. CBMC from the same CB donor were stimulated with pp65 - expressing BLCL (BLCLpp65) weekly for 5 - 6 weeks. Chromium release assays (CRA) were performed to detect the specific cytotoxicity of the CTL against EBV and CMV. RESULTS: Western blot analysis and immunocytochemistry confirmed that BLCLpp65 could simultaneously express CMVpp65 and EBV antigen. CRA results showed that the generated CTL possessed specific cytotoxic against EBV and CMV, and the cytotoxicity was mediated by CD8+ CTL. CONCLUSION: BLCLpp65 can be used as antigen - presenting cells to stimulate expansion of EBV and CMV specific CTL simultaneously from the predominantly native T cell population in CB.
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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.