OBJECTIVE: To investigate the response of multiple myeloma (MM) cells to arsenic trioxide (As2O3) and their possible mechanisms. METHODS: Two MM-derived cell lines RPMI8226 and U266 cells were used as in vitro models....OBJECTIVE: To investigate the response of multiple myeloma (MM) cells to arsenic trioxide (As2O3) and their possible mechanisms. METHODS: Two MM-derived cell lines RPMI8226 and U266 cells were used as in vitro models. Cell apoptosis was assessed by morphology, flow cytometry, and DNA gel electrophoresis. Mitochondrial transmembrane potentials (delta psi m) were evaluated by measuring cellular Rhodamine 123 staining intensity. Protein expression was analyzed using Western blot. RESULTS: Zero point one to 0.5 mumol/L As2O3 inhibited cell proliferation and 2.0 mumol/L As2O3 induced cell apoptosis, while 1.0 mumol/L As2O3 inhibited proliferation with a weak degree of apoptosis induction in RPMI8226 and U266 cell lines. As2O3-induced apoptosis was accompanied by mitochondrial transmembrane potentials (delta psi m) collapse and caspase-3 activation in the presence of intact membrane. Glutathione depleter buthionine sulfoximine enhanced, while disulfide bond-reducing agent dithiothreitol partially antagonized As2O3-induced delta psi m collapse and apoptosis in MM cells. All-trans retinoic acid (ATRA) could also induce apoptosis in RPMI8226 cells, but it did not show any cooperative effects with As2O3. CONCLUSION: As2O3 exerts apoptosis-inducing and growth-inhibiting effects on MM cells, and mitochondrium is a pivotal and common target of As2O3 for apoptosis induction.展开更多
Background Although previous clinical study revealed that bortezomib combined with dexamethasone had improved the outcomes of relapsed or refractory multiple myeloma （RRMM）, the optimal dose combinations of bortezom...Background Although previous clinical study revealed that bortezomib combined with dexamethasone had improved the outcomes of relapsed or refractory multiple myeloma （RRMM）, the optimal dose combinations of bortezomib and dexamethasone remain unknown. This trial aimed to observe the efficacy and safety of different dose combinations of bortezomib and dexamethasone in the treatment of RRMM patients in China.Methods A total of 168 patients with relapsed multiple myeloma （MM） who were refractory to at lest two prior treatments were enrolled in this multicenter, open-label, non-randomized, prospective clinical trial. Twenty patients received 1.3 mg/m2 of bortezomib twice weekly for 2 weeks of a 3-week cycle for up to 8 cycles and oral or intravenous dexamethasone 20 mg on the day of and after each bortezomib dose （group 1）; 66 patients received less than 1.3 mg/m2（0.7-1.0 mg/m2） of bortezomib and dexamethasone 20 mg on the same schedule （group 2）; 37 patients received 1.3 mg/m2 of bortezomib and dexamethasone 40 mg （group 3） and 45 patients received less than 1.3 mg/m2 （0.7-1.0 mg/m2）of bortezomib and dexamethasone 40 mg （group 4）. The response was evaluated according to the criteria of the European Group for Blood and Marrow Transplantation and confirmed by an independent review committee. Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria, version 3.0. Results The median age of groups 1 to 4 was 61,62, 56, and 60 years, respectively. Most patients were in stages Ⅱ/Ⅲ of MM and the most common subtype was IgG The rate of overall response to bortezomib and dexamethasone of group 1 to 4 was 72.2% （13/18）, 73.8% （48/65）, 78.8% （26/33） and 78.0% （32/41） （P=0.91）, including a complete response rate of 22.2% （4/18）, 20.0% （13/65）, 33.3% （11/33） and 29.3% （12/41） （P=0.67）, respectively. There was no statistical significance in time to progression and overall survival among these 4 groups （P 〉0.05）. T展开更多
Medical imaging is of crucial importance for diagnosis and initial staging as well as for differentiation of multiple myeloma(MM)from other monoclonal plasma cell diseases.Conventional radiography represents the refer...Medical imaging is of crucial importance for diagnosis and initial staging as well as for differentiation of multiple myeloma(MM)from other monoclonal plasma cell diseases.Conventional radiography represents the reference standard for diagnosis of MM due to its wide availability and low costs despite its known limitations such as low sensitivity,limited specificity and its inability to detect extraosseous lesions.Besides conventional radiography,newer cross-sectional imaging modalities such as whole-body low-dose computed tomography(CT),whole-body magnetic resonance imaging(MRI)and18F-fluorodeoxyglucose(FDG)positron emission tomography(PET)/CT are available for the diagnosis of osseous and extraosseous manifestations of MM.Whole-body low-dose CT is used increasingly,replacing conventional radiography at selected centers,due to its higher sensitivity for the detection of osseous lesions and its ability to diagnose extraosseous lesions.The highest sensitivity for both detection of bone marrow disease and extraosseous lesions can be achieved with whole-body MRI and18F-FDG PET/CT.According to current evidence,MRI is the most sensitive method for initial staging while18F-FDG PET/CT allows monitoring of treatment of MM.There is an evolving role for assessment of treatment response using newer MR imagingtechniques.Future studies are needed to further define the exact role of the different imaging modalities for individual risk stratification and therapy monitoring.展开更多
Background Chromosomal abnormalities have been shown to play an important prognostic role in multiple myeloma （MM）. Interphase fluorescence in situ hybridization （i-FISH） has been much more effective to identify c...Background Chromosomal abnormalities have been shown to play an important prognostic role in multiple myeloma （MM）. Interphase fluorescence in situ hybridization （i-FISH） has been much more effective to identify cytogenetic aberrations in MM than conventional cytogenetic technique （CC）. To clearly determine the cytogenetic features of Chinese MM patients and identify their prognostic implications, we designed a multicenter study based on i-FISH including 672 patients from 52 hospitals in China. Methods All 672 patients were systematically screened for the following genomic aberrations： del（13q）, IgH rearrangement, del（p53） and lq21 amplifications. Results The analysis showed that the chromosomal changes were detected in 22.1% patients by CC and in 82.3% patients by i-FISH. The most common abnormalities by CC were chromosome 1 aberrations （48.4%）, -13/13q- （37.6%）, hyperdiploidy （36.6%）, hypodiploidy （30.1%） and IgH rearrangements （23.7%）. The most frequent abnormalities by FISH was del（13q）, which was found in 60.4% patients, whereas IgH rearrangement, lq21 amplification and p53 deletions were detected in 57.6%, 49.0% and 34.7% cases, respectively. By statistical analysis, -13/13q- by CC was associated with low level of platelet （P=0.015）, hyperdiploidy was associated with low level of serum albumin （P=0.028）, and IgH rearrangement by FISH was associated with high level of 132 microglobulin （P=0.019）. Moreover, lq21 amplification and del（p53） by FISH conferred a high incidence of progressive disease （PD） after initial therapy. Metaphase detection of IgH rearrangements and chromosome 1 aberrations concurrently was associated with a short progression free survival （PFS） （P=-0.036）. No significant prognostic implications of other cytogenetic abnormalities were found associated with overall survival and PFS. Conclusions Chinese MM patients had similar cytogenetic abnormalities compared with the previous reported studies. However, the prognostic展开更多
Background Previous studies found a range of prognostic factors but no consensus about the proper staging system for multiple myeloma has been achieved. This study explored the prognostic factors to find a staging sys...Background Previous studies found a range of prognostic factors but no consensus about the proper staging system for multiple myeloma has been achieved. This study explored the prognostic factors to find a staging system for multiple myeloma most suitable for Chinese patients. Methods Between February 1990 to August 2004, 206 patients （138 men and 68 women, mean aged （59±11） years） who were initially diagnosed as multiple myeloma in Changzheng Hospital （Shanghai, China） and had followup records were enrolled in this study. Potential prognostic factors were evaluated by univariate and multivariate analyses. Four staging systems were applied to compare their suitability for the patients. Results The median survival time of the patients was 33 months. The 1-, 3- and 5-year survival rates were 80.18%, 48.08% and 33.7% respectively. Factors identified as adversely affecting survival were older age, severe bone lesions, low haemoglobin, low platelet, low serum calcium, low serum albumin, high proportion of plasma cells in marrow, high serum creatinine, high serum β2 microglobulin and high C-reactive protein. Among these, only C-reactive protein, β2 microglobulin, albumin and age were the independent prognostic factors. There were statistically significant survival differences among the three groups in Durie Salmon staging system and Bataille staging system, but not in British Medical Research Council staging system or International Staging System. Conclusions High β2 microglobulin, high C-reactive protein, low albumin and old age are independent prognostic factors of multiple myeloma. Bataille staging system appears to be optimal for Chinese multiple myeloma patients.展开更多
This review summarizes the therapeutic strategies and the drugs actually in development for the management of myeloma patients. Multiple myeloma is caused by the expansion of monoclonal plasma cells and secretion of M...This review summarizes the therapeutic strategies and the drugs actually in development for the management of myeloma patients. Multiple myeloma is caused by the expansion of monoclonal plasma cells and secretion of M-protein(immunoglobulins, Bence Jones protein and free light chains). Multiple myeloma still remains an incurable disease with a high incidence rate in the elderly, despite the introduction of several new therapeutic agents(bortezomib, lenalidomide and thalidomide) which have changed its natural history. The high heterogeneity of this disease leads to large differences in clinical responses to treatments. Thus, the choice of the best treatment is a difficult issue. However, the introduction of new drugs has made it possible to achieve high response rates and good quality respons-es with long-term disease control. Interactions between tumor cells and their bone marrow microenvironment play a pivotal role in the development, maintenance, and progression of myeloma, inducing also drug resistance. These knowledges have improved treatment options, leading to the approval of new drugs which not only target the malignant cell itself, but also its microenvironment. These agents are in preclinical/early clinical evaluation and they appear to further improve disease control, but their use is still not approved outside of clinical trials.展开更多
BACKGROUND The guiding effect of prognostic stratification in multiple myeloma(MM) for treatment has been increasingly emphasized in recent years. The stratification of risk factors based on the International Staging ...BACKGROUND The guiding effect of prognostic stratification in multiple myeloma(MM) for treatment has been increasingly emphasized in recent years. The stratification of risk factors based on the International Staging System(ISS), Durie-Salmon(DS)staging and related indicators is affected by the renal function of patients,resulting in poor performance. This study assesses the relationship between interleukin-32(IL-32) and related risk factors in 67 patients with MM and their clinical outcomes.AIM To investigate the feasibility of IL-32 in evaluating prognosis in patients with MM and the factors influencing prognosis.METHODS This was a pragmatic, prospective observational study of patients with MM at a single center. According to IL-32 level, patients were divided into two groups.The variables under consideration included age, blood β2-microglobulin,albumin, C-reactive protein, serum calcium, serum creatinine, lactate dehydrogenase, M protein type, ISS stage, DS stage, and IL-32 levels and minimal residual disease(MRD) after induction treatment. The main outcomes were progression-free survival(PFS) and overall survival(OS).RESULTS IL-32 was an important factor affecting PFS and OS in patients with MM.Compared with patients with IL-32 levels ≥ 856.4 pg/m L, patients with IL-32 levels < 856.4 pg/m L had longer PFS(P = 0.0387) and OS(P = 0.0379);Univariate analysis showed that IL-32 level and MRD were significantly associated with OS and PFS(P < 0.05). Multivariate analysis showed that IL-32 levels ≥ 856.4 pg/m L and MRD positive were still independent risk factors for OS and PFS(P < 0.05).CONCLUSION IL-32 is valuable for assessing the prognosis of MM patients. IL-32 level combined with MRD may be a useful routine evaluation index for MM patients after treatment.展开更多
Background： Elderly multiple myeloma （MM） patients often tend to suffer a variety of diseases, so the treatment of choice is very difficult for the elderly myeloma patients. The overall survival （OS） time and sid...Background： Elderly multiple myeloma （MM） patients often tend to suffer a variety of diseases, so the treatment of choice is very difficult for the elderly myeloma patients. The overall survival （OS） time and side effects with elderly patients are unclear in China. The study tried to find out the role of geriatric assessment in the Chinese elderly MM. Methods： We retrospectively analyzed the data of 628 newly diagnosed patients from six hospitals from June 2011 to June 2013. A geriatric assessment had been performed to assess comorbidities, cognitive, and physical status for these patients. The primary endpoint was to evaluate different physical states of elderly patients with OS time and treatment-related side effects. Results： An additive scoring system （range： 0-5）, based on age, Katz＇s Activity of Daily Living （ADL） and Lawton＇s Instrumental Activity of Daily Living （IADL） 〈5 and Charlson Comorbidity Index （CC1） was developed to identify three groups： fit （score = 0）; intermediate-fitness （score = 1 ）; and fi＇ail （score ≥2）. The 3-year OS was 63% in fit patients, 63% in intermediate-fimess patients, and 49% in frail patients ≥3 hematologic adverse events （AEs） were documented in 45 （35.4%） fit, 34 （34%） intermediate-fitness, and 121 （30.2%） frail patients. The risk of a grade ≥3 hematologic AEs was not significantly increase in intermediate-fitness （hazard ratios [HR]： 0.99, 95% confidence interval [CI]： 0.54 1.47, P = 1.000） and in frail patients （tfR： 1.16, 95% CI： 0.70-1.93, P- 0.558） compared with fit ones. Conclusions： MM occurs earlier in life and being advanced when the diagnosis is made in the mainland of China. The overall survival in fi＇ailty with International Staging System （ISS） ll/lll was the worst in all patients.展开更多
Background Chromosome 13q14 deletion （del13q14）, chromosome 1q21 gain （amp1q21） and chromosome 17p13 deletion （del17p13） are the most frequent chromosomal aberrations in multiple myeloma （MM）. They play an imp...Background Chromosome 13q14 deletion （del13q14）, chromosome 1q21 gain （amp1q21） and chromosome 17p13 deletion （del17p13） are the most frequent chromosomal aberrations in multiple myeloma （MM）. They play an important role in prognosis. The aim of this study was to investigate the clinical significance of the chromosomal changes in Chinese MM patients.Methods Interphase fluorescence in situ hybridization （FISH） on bone marrow （BM） cells was performed in 72 enrolled MM patients. Relationships between chromosomal abnormalities and clinical features, response to therapies and prognosis were analyzed.Results As a result of interphase FISH, 77.8% （56/72） patients had chromosome changes. The incidences of each probe were RB1 51.4% （37/72）, D13S319 47.2% （34/72）, 1q21 45.8% （33/72） and p53 22.2% （12/72）. Osteolytic lesion,BM plasma cells index, serum calcium and serum M component were significantly correlated to del13q14. BM plasma cells and hemoglobin were correlated to amp1q21. Serum lactate dehydrogenase （LDH） was correlated with del17p13.Patients with del13q14 treated with bortezomib had a notably higher overall response rate than the patients treated with traditional chemotherapies （93% vs. 65%, P=0.048）. Patients carrying amp1q21 or/and del17p13 did not achieve satisfactory response to bortezomib. The median progression-free survival （PFS） for patients with amp1q21 was 5 months and patients without amp1q21 got 9-month PFS （P=0.001）. The median PFS for patients with del13q14 was 5 months （vs. 8 months, P=0.026）. The median PFS for patients with del17p13 was 3 months （vs. 8 months, P=0.002）.Patients with β2-microglobulin 〉5.5 mg/L also had a worse outcome, whose median PFS was 5 months （vs. 8 months,P=0.016）.Conclusions The prevalence of chromosomal abnormalities of MM patients was similar in Chinese and Caucasian people. Genetic changes were associated with patients＇ responses to therapies and prognosis.展开更多
Background Although neurologic manifestations often complicate the course of patients with multiple myeloma, direct central nervous system invasion is rare. This study explored the neurologic symptoms, signs, clinical...Background Although neurologic manifestations often complicate the course of patients with multiple myeloma, direct central nervous system invasion is rare. This study explored the neurologic symptoms, signs, clinical features, therapy and prognosis of Chinese patients with central nervous system myeloma invasion. Methods The diagnosis, therapy and prognosis were analyzed retrospectively in 11 Chinese multiple myeloma patients with central nervous system infiltration from a total of 625 patients who have been treated at Changzheng Hospital （Shanghai, China） between January 1993 and May 2009. Survival curve was constructed with the use of Kaplan-Meier estimates. Results There were 11 patients with central nervous system involvement from 625 multiple myeloma patients. The occurrence rate was 1.8%. Ten of the 11 patients had other extramedullary diseases. Symptoms included cerebral symptoms, cranial nerve palsies, and spinal cord or spinal nerve roots symptoms. Cerebrospinal fluid was abnormal in 7 patients, usually exhibiting pleocytosis and elevated protein content, plus positive cytologic findings. Specific magnetic resonance imaging findings suggestive of central nervous system invasion were found in 9 patients. After a median follow-up of 19 months, 3 patients were alive. The median overall survival for all patients was 23 months, while the median overall survival for patients after central nervous system invasion was merely 6 months. Conclusions It is exceedingly rare for there to be central nervous system infiltration in multiple myeloma patients. When it occurs, the prognosis is extremely poor despite the use of aggressive local and systemic treatment including stem cell transplantation.展开更多
基金theNationalNaturalScienceFoundationofChina (No 39970 312andNo 39730 2 70 ) NationalOutstandingYoungScientificFoundationofC
文摘OBJECTIVE: To investigate the response of multiple myeloma (MM) cells to arsenic trioxide (As2O3) and their possible mechanisms. METHODS: Two MM-derived cell lines RPMI8226 and U266 cells were used as in vitro models. Cell apoptosis was assessed by morphology, flow cytometry, and DNA gel electrophoresis. Mitochondrial transmembrane potentials (delta psi m) were evaluated by measuring cellular Rhodamine 123 staining intensity. Protein expression was analyzed using Western blot. RESULTS: Zero point one to 0.5 mumol/L As2O3 inhibited cell proliferation and 2.0 mumol/L As2O3 induced cell apoptosis, while 1.0 mumol/L As2O3 inhibited proliferation with a weak degree of apoptosis induction in RPMI8226 and U266 cell lines. As2O3-induced apoptosis was accompanied by mitochondrial transmembrane potentials (delta psi m) collapse and caspase-3 activation in the presence of intact membrane. Glutathione depleter buthionine sulfoximine enhanced, while disulfide bond-reducing agent dithiothreitol partially antagonized As2O3-induced delta psi m collapse and apoptosis in MM cells. All-trans retinoic acid (ATRA) could also induce apoptosis in RPMI8226 cells, but it did not show any cooperative effects with As2O3. CONCLUSION: As2O3 exerts apoptosis-inducing and growth-inhibiting effects on MM cells, and mitochondrium is a pivotal and common target of As2O3 for apoptosis induction.
文摘Background Although previous clinical study revealed that bortezomib combined with dexamethasone had improved the outcomes of relapsed or refractory multiple myeloma （RRMM）, the optimal dose combinations of bortezomib and dexamethasone remain unknown. This trial aimed to observe the efficacy and safety of different dose combinations of bortezomib and dexamethasone in the treatment of RRMM patients in China.Methods A total of 168 patients with relapsed multiple myeloma （MM） who were refractory to at lest two prior treatments were enrolled in this multicenter, open-label, non-randomized, prospective clinical trial. Twenty patients received 1.3 mg/m2 of bortezomib twice weekly for 2 weeks of a 3-week cycle for up to 8 cycles and oral or intravenous dexamethasone 20 mg on the day of and after each bortezomib dose （group 1）; 66 patients received less than 1.3 mg/m2（0.7-1.0 mg/m2） of bortezomib and dexamethasone 20 mg on the same schedule （group 2）; 37 patients received 1.3 mg/m2 of bortezomib and dexamethasone 40 mg （group 3） and 45 patients received less than 1.3 mg/m2 （0.7-1.0 mg/m2）of bortezomib and dexamethasone 40 mg （group 4）. The response was evaluated according to the criteria of the European Group for Blood and Marrow Transplantation and confirmed by an independent review committee. Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria, version 3.0. Results The median age of groups 1 to 4 was 61,62, 56, and 60 years, respectively. Most patients were in stages Ⅱ/Ⅲ of MM and the most common subtype was IgG The rate of overall response to bortezomib and dexamethasone of group 1 to 4 was 72.2% （13/18）, 73.8% （48/65）, 78.8% （26/33） and 78.0% （32/41） （P=0.91）, including a complete response rate of 22.2% （4/18）, 20.0% （13/65）, 33.3% （11/33） and 29.3% （12/41） （P=0.67）, respectively. There was no statistical significance in time to progression and overall survival among these 4 groups （P 〉0.05）. T
文摘Medical imaging is of crucial importance for diagnosis and initial staging as well as for differentiation of multiple myeloma(MM)from other monoclonal plasma cell diseases.Conventional radiography represents the reference standard for diagnosis of MM due to its wide availability and low costs despite its known limitations such as low sensitivity,limited specificity and its inability to detect extraosseous lesions.Besides conventional radiography,newer cross-sectional imaging modalities such as whole-body low-dose computed tomography(CT),whole-body magnetic resonance imaging(MRI)and18F-fluorodeoxyglucose(FDG)positron emission tomography(PET)/CT are available for the diagnosis of osseous and extraosseous manifestations of MM.Whole-body low-dose CT is used increasingly,replacing conventional radiography at selected centers,due to its higher sensitivity for the detection of osseous lesions and its ability to diagnose extraosseous lesions.The highest sensitivity for both detection of bone marrow disease and extraosseous lesions can be achieved with whole-body MRI and18F-FDG PET/CT.According to current evidence,MRI is the most sensitive method for initial staging while18F-FDG PET/CT allows monitoring of treatment of MM.There is an evolving role for assessment of treatment response using newer MR imagingtechniques.Future studies are needed to further define the exact role of the different imaging modalities for individual risk stratification and therapy monitoring.
文摘Background Chromosomal abnormalities have been shown to play an important prognostic role in multiple myeloma （MM）. Interphase fluorescence in situ hybridization （i-FISH） has been much more effective to identify cytogenetic aberrations in MM than conventional cytogenetic technique （CC）. To clearly determine the cytogenetic features of Chinese MM patients and identify their prognostic implications, we designed a multicenter study based on i-FISH including 672 patients from 52 hospitals in China. Methods All 672 patients were systematically screened for the following genomic aberrations： del（13q）, IgH rearrangement, del（p53） and lq21 amplifications. Results The analysis showed that the chromosomal changes were detected in 22.1% patients by CC and in 82.3% patients by i-FISH. The most common abnormalities by CC were chromosome 1 aberrations （48.4%）, -13/13q- （37.6%）, hyperdiploidy （36.6%）, hypodiploidy （30.1%） and IgH rearrangements （23.7%）. The most frequent abnormalities by FISH was del（13q）, which was found in 60.4% patients, whereas IgH rearrangement, lq21 amplification and p53 deletions were detected in 57.6%, 49.0% and 34.7% cases, respectively. By statistical analysis, -13/13q- by CC was associated with low level of platelet （P=0.015）, hyperdiploidy was associated with low level of serum albumin （P=0.028）, and IgH rearrangement by FISH was associated with high level of 132 microglobulin （P=0.019）. Moreover, lq21 amplification and del（p53） by FISH conferred a high incidence of progressive disease （PD） after initial therapy. Metaphase detection of IgH rearrangements and chromosome 1 aberrations concurrently was associated with a short progression free survival （PFS） （P=-0.036）. No significant prognostic implications of other cytogenetic abnormalities were found associated with overall survival and PFS. Conclusions Chinese MM patients had similar cytogenetic abnormalities compared with the previous reported studies. However, the prognostic
文摘Background Previous studies found a range of prognostic factors but no consensus about the proper staging system for multiple myeloma has been achieved. This study explored the prognostic factors to find a staging system for multiple myeloma most suitable for Chinese patients. Methods Between February 1990 to August 2004, 206 patients （138 men and 68 women, mean aged （59±11） years） who were initially diagnosed as multiple myeloma in Changzheng Hospital （Shanghai, China） and had followup records were enrolled in this study. Potential prognostic factors were evaluated by univariate and multivariate analyses. Four staging systems were applied to compare their suitability for the patients. Results The median survival time of the patients was 33 months. The 1-, 3- and 5-year survival rates were 80.18%, 48.08% and 33.7% respectively. Factors identified as adversely affecting survival were older age, severe bone lesions, low haemoglobin, low platelet, low serum calcium, low serum albumin, high proportion of plasma cells in marrow, high serum creatinine, high serum β2 microglobulin and high C-reactive protein. Among these, only C-reactive protein, β2 microglobulin, albumin and age were the independent prognostic factors. There were statistically significant survival differences among the three groups in Durie Salmon staging system and Bataille staging system, but not in British Medical Research Council staging system or International Staging System. Conclusions High β2 microglobulin, high C-reactive protein, low albumin and old age are independent prognostic factors of multiple myeloma. Bataille staging system appears to be optimal for Chinese multiple myeloma patients.
基金Supported by Associazione Italiana per la Ricerca sul Cancro(Italian Association for Cancer Research-AIRC),Investigator Grant and the 5 per thousand Molecular Clinical Oncology Special Program,No.9965Milan,to AV,the European Commission's Seventh Framework programme(EU-FPT7)under grant agreement(OVER-My R)to AV,No.278706+2 种基金EU FPT7(2007-2013)under grant agreement to DR,No.278570grants from MIUR PRIN to RR,No.2009WCNS5C_004grants from MIUR PRIN to AV,No.2010NECHBX
文摘This review summarizes the therapeutic strategies and the drugs actually in development for the management of myeloma patients. Multiple myeloma is caused by the expansion of monoclonal plasma cells and secretion of M-protein(immunoglobulins, Bence Jones protein and free light chains). Multiple myeloma still remains an incurable disease with a high incidence rate in the elderly, despite the introduction of several new therapeutic agents(bortezomib, lenalidomide and thalidomide) which have changed its natural history. The high heterogeneity of this disease leads to large differences in clinical responses to treatments. Thus, the choice of the best treatment is a difficult issue. However, the introduction of new drugs has made it possible to achieve high response rates and good quality respons-es with long-term disease control. Interactions between tumor cells and their bone marrow microenvironment play a pivotal role in the development, maintenance, and progression of myeloma, inducing also drug resistance. These knowledges have improved treatment options, leading to the approval of new drugs which not only target the malignant cell itself, but also its microenvironment. These agents are in preclinical/early clinical evaluation and they appear to further improve disease control, but their use is still not approved outside of clinical trials.
基金Supported by Foundation for Excellent Young Medical Talents from the Quzhou People’s Hospital
文摘BACKGROUND The guiding effect of prognostic stratification in multiple myeloma(MM) for treatment has been increasingly emphasized in recent years. The stratification of risk factors based on the International Staging System(ISS), Durie-Salmon(DS)staging and related indicators is affected by the renal function of patients,resulting in poor performance. This study assesses the relationship between interleukin-32(IL-32) and related risk factors in 67 patients with MM and their clinical outcomes.AIM To investigate the feasibility of IL-32 in evaluating prognosis in patients with MM and the factors influencing prognosis.METHODS This was a pragmatic, prospective observational study of patients with MM at a single center. According to IL-32 level, patients were divided into two groups.The variables under consideration included age, blood β2-microglobulin,albumin, C-reactive protein, serum calcium, serum creatinine, lactate dehydrogenase, M protein type, ISS stage, DS stage, and IL-32 levels and minimal residual disease(MRD) after induction treatment. The main outcomes were progression-free survival(PFS) and overall survival(OS).RESULTS IL-32 was an important factor affecting PFS and OS in patients with MM.Compared with patients with IL-32 levels ≥ 856.4 pg/m L, patients with IL-32 levels < 856.4 pg/m L had longer PFS(P = 0.0387) and OS(P = 0.0379);Univariate analysis showed that IL-32 level and MRD were significantly associated with OS and PFS(P < 0.05). Multivariate analysis showed that IL-32 levels ≥ 856.4 pg/m L and MRD positive were still independent risk factors for OS and PFS(P < 0.05).CONCLUSION IL-32 is valuable for assessing the prognosis of MM patients. IL-32 level combined with MRD may be a useful routine evaluation index for MM patients after treatment.
文摘Background： Elderly multiple myeloma （MM） patients often tend to suffer a variety of diseases, so the treatment of choice is very difficult for the elderly myeloma patients. The overall survival （OS） time and side effects with elderly patients are unclear in China. The study tried to find out the role of geriatric assessment in the Chinese elderly MM. Methods： We retrospectively analyzed the data of 628 newly diagnosed patients from six hospitals from June 2011 to June 2013. A geriatric assessment had been performed to assess comorbidities, cognitive, and physical status for these patients. The primary endpoint was to evaluate different physical states of elderly patients with OS time and treatment-related side effects. Results： An additive scoring system （range： 0-5）, based on age, Katz＇s Activity of Daily Living （ADL） and Lawton＇s Instrumental Activity of Daily Living （IADL） 〈5 and Charlson Comorbidity Index （CC1） was developed to identify three groups： fit （score = 0）; intermediate-fitness （score = 1 ）; and fi＇ail （score ≥2）. The 3-year OS was 63% in fit patients, 63% in intermediate-fimess patients, and 49% in frail patients ≥3 hematologic adverse events （AEs） were documented in 45 （35.4%） fit, 34 （34%） intermediate-fitness, and 121 （30.2%） frail patients. The risk of a grade ≥3 hematologic AEs was not significantly increase in intermediate-fitness （hazard ratios [HR]： 0.99, 95% confidence interval [CI]： 0.54 1.47, P = 1.000） and in frail patients （tfR： 1.16, 95% CI： 0.70-1.93, P- 0.558） compared with fit ones. Conclusions： MM occurs earlier in life and being advanced when the diagnosis is made in the mainland of China. The overall survival in fi＇ailty with International Staging System （ISS） ll/lll was the worst in all patients.
文摘Background Chromosome 13q14 deletion （del13q14）, chromosome 1q21 gain （amp1q21） and chromosome 17p13 deletion （del17p13） are the most frequent chromosomal aberrations in multiple myeloma （MM）. They play an important role in prognosis. The aim of this study was to investigate the clinical significance of the chromosomal changes in Chinese MM patients.Methods Interphase fluorescence in situ hybridization （FISH） on bone marrow （BM） cells was performed in 72 enrolled MM patients. Relationships between chromosomal abnormalities and clinical features, response to therapies and prognosis were analyzed.Results As a result of interphase FISH, 77.8% （56/72） patients had chromosome changes. The incidences of each probe were RB1 51.4% （37/72）, D13S319 47.2% （34/72）, 1q21 45.8% （33/72） and p53 22.2% （12/72）. Osteolytic lesion,BM plasma cells index, serum calcium and serum M component were significantly correlated to del13q14. BM plasma cells and hemoglobin were correlated to amp1q21. Serum lactate dehydrogenase （LDH） was correlated with del17p13.Patients with del13q14 treated with bortezomib had a notably higher overall response rate than the patients treated with traditional chemotherapies （93% vs. 65%, P=0.048）. Patients carrying amp1q21 or/and del17p13 did not achieve satisfactory response to bortezomib. The median progression-free survival （PFS） for patients with amp1q21 was 5 months and patients without amp1q21 got 9-month PFS （P=0.001）. The median PFS for patients with del13q14 was 5 months （vs. 8 months, P=0.026）. The median PFS for patients with del17p13 was 3 months （vs. 8 months, P=0.002）.Patients with β2-microglobulin 〉5.5 mg/L also had a worse outcome, whose median PFS was 5 months （vs. 8 months,P=0.016）.Conclusions The prevalence of chromosomal abnormalities of MM patients was similar in Chinese and Caucasian people. Genetic changes were associated with patients＇ responses to therapies and prognosis.
文摘Background Although neurologic manifestations often complicate the course of patients with multiple myeloma, direct central nervous system invasion is rare. This study explored the neurologic symptoms, signs, clinical features, therapy and prognosis of Chinese patients with central nervous system myeloma invasion. Methods The diagnosis, therapy and prognosis were analyzed retrospectively in 11 Chinese multiple myeloma patients with central nervous system infiltration from a total of 625 patients who have been treated at Changzheng Hospital （Shanghai, China） between January 1993 and May 2009. Survival curve was constructed with the use of Kaplan-Meier estimates. Results There were 11 patients with central nervous system involvement from 625 multiple myeloma patients. The occurrence rate was 1.8%. Ten of the 11 patients had other extramedullary diseases. Symptoms included cerebral symptoms, cranial nerve palsies, and spinal cord or spinal nerve roots symptoms. Cerebrospinal fluid was abnormal in 7 patients, usually exhibiting pleocytosis and elevated protein content, plus positive cytologic findings. Specific magnetic resonance imaging findings suggestive of central nervous system invasion were found in 9 patients. After a median follow-up of 19 months, 3 patients were alive. The median overall survival for all patients was 23 months, while the median overall survival for patients after central nervous system invasion was merely 6 months. Conclusions It is exceedingly rare for there to be central nervous system infiltration in multiple myeloma patients. When it occurs, the prognosis is extremely poor despite the use of aggressive local and systemic treatment including stem cell transplantation.
