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1.
Pol Merkur Lekarski ; 48(287): 344-345, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33130796

RESUMO

Multiple myeloma (MM) ) is a malignant plasma cell disorder from the group of monoclonal gammopathies. One of the most frequent diagnostic findings is the M-spike in serum protein electrophoresis (SPEP), which is notably absent in a rare non-secretory subtype of this disease. A CASE REPORT: A case report describes a 55-year old woman with a history of chronic kidney disease (CKD) in stage 3, proteinuria, asthma and Graves' disease. She presented for a diagnosis of proteinuria (of 2,2 g/24 h). Her SPEP was normal, and she underwent a kidney biopsy, which showed mild glomerulal abnormalities. She returned to the clinic after 5 years with progression of CKD (between hospitalizations creatinine rose from 1,27 mg/dl to 2,8) and proteinuria (2,7 g/24 h). She had normocytic anemia, normocalcemia and normal ESR. The SPEP showed no suspicious findings, but suspecting multiple myeloma, immunofixation was performed. It showed excessive levels of kappa FLC in serum and urine. A bone marrow biopsy showed plasmocytes characteristic for MM in both number and phenotype. No osteolytic lesions were shown in diagnostic imaging, and beta-2-microglobulin was elevated to 6,5 µg. Thus, the patient was diagnosed with ISS stage 3 multiple myeloma and referred to a hematology clinic for treatment. CONCLUSIONS: The diagnosis of atypical cases of multiple myeloma may pose a difficulty to clinicians. Knowledge of diagnostic tests is required to introduce proper treatment.


Assuntos
Mieloma Múltiplo , Insuficiência Renal Crônica , Feminino , Humanos , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Insuficiência Renal Crônica/complicações
2.
Zhonghua Bing Li Xue Za Zhi ; 49(11): 1136-1141, 2020 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-33152818

RESUMO

Objective: To investigate the relationship between six common cytogenetic abnormalities and bone marrow pathomorphology in multiple myeloma (MM). Methods: Bone marrow biopsy was performed on 151 newly-diagnosed MM patients. Meanwhile, myeloma cells were enriched by CD138 immunomagnetic beads, and then lq+, 13q-, 17p-, t(4;14), t (11;14), t (14;16) and other common genetic abnormalities were detected using interphase fluorescence in situ hybridization (FISH). The relationship between different genetic abnormalities and biopsy morphology was compared. Results: Of the 151 patients, 15 had extramedullary infiltration (9.9%). The rate of cytogenetic abnormalities was 76.2% (115/151), of which 1q+ accounted for 49.7% (75/151), 13q-39.1% (59/151), 17p-8.6% (13/151), t(4;14) 21.2% (32/151), t(11;14) 19.2% (29/151), and t(14;16) 2.0% (3/151). The proliferation patterns of MM plasma cells were nodular (48.3%, 73/151), interstitial (33.8%, 51/151) and diffuse (17.9%, 27/151). The morphology of plasma cells was mainly mature type (58.3%, 88/151), followed by juvenile type (20.5%, 31/151), intermediate type (15.9%, 24/151) and plasmacyte type (5.3%, 8/151). According to the mSMART risk stratification system, the proliferation pattern of myeloma cells in the high-risk group was mainly diffuse type, and the morphology was mainly immature and plasmacyte type. In the middle-risk group, mature type myeloma cells were mainly nodular proliferating. In the low-risk and negative group, mature type myeloma cells were mainly interstitial proliferating. There was no difference in the probability of different proliferation modes of intermediate type plasma cells in each group. Conclusions: The proliferation pattern and morphology of plasma cells in bone marrow biopsy combined with cytogenetic markers can more accurately predict the severity and prognosis of MM.


Assuntos
Mieloma Múltiplo , Adolescente , Medula Óssea , Aberrações Cromossômicas , Humanos , Hibridização in Situ Fluorescente , Mieloma Múltiplo/genética , Plasmócitos , Prognóstico
3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1592-1597, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067959

RESUMO

OBJECTIVE: To explore the role of interaction between osteoclast stimulator stromal derived factor 1 alpha (SDF-1α) and osteoblast inhibitor dickkopf-1 (DKK-1) in the development of multiple myeloma (MM) bone disease. METHODS: The serum samples of 51 patients with newly diagnosed MM, 30 age-matched healthy controls, and 35 non-Hodgkin lymphoma patients from June 2011 to May 2014 in Peking Union Medical College Hospital were collected. The serum SDF-1α and DKK-1 were detected by ELISA. Primary myeloma cells and human MM cell line RPMI 8226 were treated with SDF-1α, then DKK-1 mRNA expression was detected by real time PCR. Primary bone marrow stromal cells (BMSCs) were treated with Wnt-3a and/or DKK-1, and the transc-ription level of SDF-1α mRNA was assayed. RESULTS: Serum SDF-1α in MM patients was significantly higher than that in control group (3231.0±1269.5 pg/ml vs 2817.5±419.6 pg/ml)(P=0.036), so was serum DKK-1 (3057.4±1874.7 pg/ml vs 1867.7±1148.4 pg/ml)(P=0.01). There was a positive correlation between serum SDF-1α and DKK-1 in MM patients (r=0.301, P=0.032), but there was no correlation between control group (r=0.15, P=0.428) and non-Hodgkin lymphoma patients (r=0.227, P=0.095). After treated with SDF-1α (20 ng/ml) for 8 and 36 h, the DKK-1 mRNA transcription level in RPMI 8226 increased by 1.92 and 4.19-folds respectively(P=0.365, P=0.099). Moreover, the high transcription level of DKK-1 mRNA was observed in 5 out of 9 MM patients. The detection showed that after treatment with SDF-1α, the transcription level was up-regulated(P=0.043), the Wnt-3a (200 ng/ml) could decrease the expression of SDF-1α mRNA in primary BMSC to 29% of baseline(P=0.028), the adding DKK-1 could reverse the down-regulation effect. CONCLUSION: The serum SDF-1α and DKK-1 level in MM patients is high than normal leve, moreover shows the positive correlation between them. The SDF-1α and DKK-1 can interreact, therefore accerate the formation of MM bone disease.


Assuntos
Doenças Ósseas , Linfoma não Hodgkin , Mieloma Múltiplo , Quimiocina CXCL12 , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Osteoclastos
4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1598-1604, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067960

RESUMO

OBJECTIVE: To detect the expression of MutT homolog 1 (MTH1) in CD138-negative cells (CD138-) and CD138-positive cells (CD138+) cells of the patients with multiple myeloma (MM), and to explore the effect of MTH1 inhibitor TH588 on cell morphology, proliferation and apoptosis of MM cell U266. METHODS: CD138- and CD138+ cells of MM patients were isolated, and RNA was extracted. The expression of NUDT family was detected by Q-PCR. MM cell line U266 was used to observe the effect of IL-6 on MTH1 expression. Using fluorescence microscopy to observe the morphological changes of U266 after treatment by TH588 for 48 hours. DAPI staining was used to investigate the nuclear change. Luciferase was used to detect the effect of TH588 on U266 cell proliferation. After treatment with TH588 for 48 h, the change of apoptosis in MM U266 cells was detected by flow cytometer. RESULTS: In some MM patients, the expression of MTH1, NUDT2, NUDT5 and NUDT21 in CD138+ cells was higher than that in CD138- (P<0.05). The luciferase report showed that after treatment of U266 cells with TH588, the fluorescence intensity was significantly lower than that of the control group, and the fluorescence intensity decreased with the increase of drug concentration (r=-0.91). IL-6 could increase the expression of MTH1. Fluorescence microscopy showed that after TH588 treatment of U266 cells for 48 hours, the cells appeared shrinking, smaller, and irregular in shape. After DAPI staining, the TH588-treated cells showed apoptosis characteristics, such as nuclear shrinkage, uneven staining, petal, and radial shape. Flow cytometry showed that the proportion of U266 viable cells decreased significantly after treatment with TH588 for 48 h (P<0.05). CONCLUSION: MTH1 highly expresses in CD138+ cells of some MM patients. MTH1 expression can increase in U266 cells treated by IL-6. The MTH1 inhibitor TH588 possesses proliferation-inhibitory effect and apoptosis-inducing effect on MM cell U266.


Assuntos
Mieloma Múltiplo , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Fator de Especificidade de Clivagem e Poliadenilação , Enzimas Reparadoras do DNA , Citometria de Fluxo , Humanos , Monoéster Fosfórico Hidrolases
5.
Medicine (Baltimore) ; 99(40): e22642, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019490

RESUMO

RATIONALE: Reactivation of hepatitis B virus (HBV) after treatment with bortezomib-based regimens in HBV-positive patients with multiple myeloma (MM) has been reported in the past few years. Nevertheless, there is evidence of inhibition of HBV replication by bortezomib in transgenic mice. However, there is still no clinical evidence that bortezomib inhibits HBV. PATIENT CONCERNS: A 55-year-old MM patient with a family history of MM, who was also a chronic HBV carrier, achieved HBV clearance after treatment with a bortezomib-based regimen in combination with anti-HBV drugs. DIAGNOSES: The diagnosis was MM with chronic carrier of HBV. INTERVENTIONS: He received bortezomib-based regimen for MM as well as entecavir as a prophylaxis to prevent HBV reactivation. OUTCOMES: This patient achieved HBsAg and HBV-DNA clearance after 2 months and the remission was maintained during the next 2 years. He also achieved complete remission of MM and underwent consolidation therapy with autologous hematopoietic stem cell transplantation. LESSONS: This is the first case of MM with HBV clearance after receiving a bortezomib-based regimen combined with anti-HBV drug. Research on related mechanisms might provide new suggestions and hope for better management of HBV positive patients with MM and for the treatment of HBV patients.


Assuntos
Antineoplásicos/uso terapêutico , Antivirais/uso terapêutico , Bortezomib/uso terapêutico , Guanina/análogos & derivados , Mieloma Múltiplo/tratamento farmacológico , Protocolos Clínicos , Quimioterapia Combinada , Guanina/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Antígenos de Superfície da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/genética , Hepatite B Crônica/complicações , Hepatite B Crônica/prevenção & controle , Hepatite B Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Transplante Autólogo/métodos , Resultado do Tratamento
7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1605-1610, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067961

RESUMO

OBJECTIVE: To investigate the effect and possible mechanism of up-regulation of p-Akt by doxycycline (DOX) on myeloma cell line H929. METHODS: Multiple myeloma cell line H929 was treated with DOX at different concentrations for different times, and cell proliferation rate was measured by CCK-8 assay. The protein expression level of p-Akt, PTEN, p-PDK1, p-mTOR, p-GSK-3ß, and p-BAD was analyzed by Western blot. The mRNA levels of mTOR, BCL-2, and NF-κB was analyzed by RT-PCR. PI3K inhibitor Wortmannin was used to antagonize the up-regulation of p-Akt, and the cell proliferation and p-Akt protein expression level were analyzed by CCK-8 assay and Western blot respectively. RESULTS: DOX could inhibit the proliferation of H929 cells and up-regulate the expression of p-Akt at the same time. The protein levels of both p-PDK1 and PTEN in H929 cells did not alter significantly during DOX treatment. The expressions of p-BAD and p-GSK-3ß were up-regulated in H929 cells after treated with DOX, but the expression of p-mTOR was not altered. The mRNA levels of mTOR, BCL-2, and NF-κB in H929 were all down-regulated in H929 cells during DOX treatment. The effect up-regulating p-Akt level by DOX was suppressed when DOX combined with PI3K inhibitor Wortmannin and Wortmannin could enhance the inhibitory effect of DOX in H929 cells. CONCLUSION: DOX can activate PI3K/Akt signaling pathway in H929 cells, and antagonizing this effect of DOX may enhance its cytotoxicity to myeloma cells.


Assuntos
Mieloma Múltiplo , Apoptose , Linhagem Celular Tumoral , Doxiciclina/farmacologia , Glicogênio Sintase Quinase 3 beta , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Regulação para Cima
8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1618-1624, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067963

RESUMO

OBJECTIVE: To explore the clinical value of serum bone turnover markers including ß-CrossLaps (ß-CTx), N-MID Osteocalcin (Osteocalcin), and total procollagen type 1 amino-terminal propeptide (TP1NP) in patients with myeloma bone disease (MBD). METHODS: A total of 55 MBD patients(MBD group) and 20 healthy volunteers(control group) were selected, and the serum was collected for detecting ß-CTx, Osteocalcin and TP1NP by Roche analyzer of automated electrochemiluminescence. Meanwhile, the imaging techniques such as MRI and CT were used for evaluation of bone destruction and the damage extent in MBD patients. RESULTS: Measurement data is expressed as median (P25, P75) according to distribution characteristics of data. The detection results showed that concentrations of ß-CTx in MBD patients and control group were 0.72(0.48, 1.28) ng/mL and 0.53(0.34, 0.61) ng/mL respectively, the ß-CTx concentration in MBD patients was significantly higher than that in control group(P=0.002). The ratio ß-CTx to TP1NP (%) in MBD patients and control group was 1.50 (1.05, 3.36) and 1.25 (0.86, 1.35) respectively, the ratio in MBD patients was significantly higher than that in control group (P=0.007). The serum ß-CTx concentrations in MBD patients of localized bone destruction type and extensive bone destruction type were 0.41(0.31, 0.66) ng/mL and 1.14(0.72, 1.81) ng/mL respectively, the ß-CTx concentration in MBD patients of extensive bone destruction type was significantly higher than that in MBD patients of localized bone destruction type (P<0.001). The ratio of ß-CTx to TP1NP(%) in MBD patients of localized and extensive bone destruction type was 1.30 (0.90, 2.49) and 1.98 (1.18, 3.76) respectively, the ratio in the MBD patients of extensive bone destruction type was significantly higher than that in MBD patients of localized bone destruction type (P=0.019). The serum osteocalcin concentrations in MBD patients of localized and extensive bone destruction type were 14.31 (8.82, 19.39) ng/mL and 21.52 (14.42, 47.76) ng/mL respectively, the osteocalcin concentration in MBD patients of extensive bone destruction type was higher than that in MBD patients of localized bone destruction type (P=0.008). The AUC of ß-CTx was 0.88 (95% CI: 0.78-0.98)(P<0.001), and the cut-off value was 0.69 ng/ml in the diagnosis of extensive bone injury for MBD patients, and the sensitivity and specificity were 80.65% and 83.33% respectively. CONCLUSION: The MBD patients show bone resorption hyperthyroidism and high bone turnover. The ß-CTx and osteocalcin in serum bone turnover markers can effectively reflect the extent of bone damage in MBD patients, especially the ß-CTx is more efficient for the diagnosis of MBD patients of extensive bone destruction type. However, ß-CTx, osteocalcin and TP1NP are not relate with the MM disease progression.


Assuntos
Doenças Ósseas , Mieloma Múltiplo , Biomarcadores , Remodelação Óssea , Humanos , Osteocalcina
9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1625-1630, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067964

RESUMO

OBJECTIVE: To investigate the expression level and the clinical significance of serum interleukin-6(IL-6) , IL-10, tumor necrosis factor α(TNF-α) and ß2-microglobulin(ß2-MG) in multiple myeloma(MM) patients with different blood separation results. METHODS: The clinical data of 124 newly diagnosed MM patients (76 cases of IgG type, 48 cases of IgA type) treated in our hospital from October 2015 to October 2019 were enrolled and analyzed. The blood samples were divided into control group (the order from top to bottom is serum, separator gel and red blood cells) and abnormal group (the order from top to bottom is serum, red blood cells, separator gel and red blood cells) according to the blood separation result. The differences of expression level in serum IL-6, IL-10, TNF-α and ß2-MG were compared between the two groups, and the changes of blood separation result and different indexes were analyzed after treatment. RESULTS: Abnormal separation results were found in 21 cases (16.94%), including 13 cases of IgG type and 8 cases of IgA type. The levels of serum IL-6, IL-10, TNF-α and ß2-MG in abnormal group were significantly higher than those in control group (P<0.05) . After treatment, 85 patients in control group (103 cases) achieved complete remission (CR) or very good partial remission (VGPR) and partial remission(PR). The results of blood separation showed no change. 18 patients achieved less than PR, and the separation result in 5 patients changed from normal to abnormal separation. The blood separation of 9 patients with CR and VGPR in abnormal group (21 cases) were changed from abnormal to normal. 8 patients achieved PR, and the separation result in 6 patients were changed from abnormal to normal and 2 cases showed no change, while the blood separation showed no changes in 4 cases MM patients who achieved less than PR in abnormal group. The expression levels of IL-6, IL-10, TNF-α and ß2-MG of patients in control group transformed to abnormal blood separation result after treatment showed significantly higher than those before treatment (P<0.05) , and the levels of IL-6 and ß2-MG were significantly lower in the patients with out change in blood separation results than those before treatment (P<0.05). The serum levels of IL-6, IL-10, TNF-α and ß2-MG of patients in abnormal group transformed to normal blood separation after treatment were significantly lower than those before treatment (P<0.05), and the serum levels of IL-6, IL-10, TNF-α and ß2-MG in abnormal group with no changes in blood separation results showed not significantly different from those before treatment (P>0.05). CONCLUSION: Abnormal separation phenomenon can be found after centrifugation in patients with multiple myeloma. The expression levels of serum IL-6, IL-10, TNF-α and ß2-MG in MM patients with different blood separation results are different, which suggesting different degrees of tumor burden. The changes of blood separation result and levels of IL-6, IL-10, TNF-α and ß2-MG after treatment can predict the therapeutic effect, and also provide the experimental basis for the evaluation of disease condition and prognosis of patients with different blood separation results.


Assuntos
Interleucina-10 , Mieloma Múltiplo , Humanos , Interleucina-1 , Interleucina-6 , Fator de Necrose Tumoral alfa
10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1631-1636, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067965

RESUMO

OBJECTIVE: To investigate the influence of MRD status in newly diagnosed MM patients with VGPR and above after treatment on clinical prognosis. METHODS: Clinical data of 210 newly diagnosed MM patients with VGPR and above after treatment in Fifth People's Hospital of Chendu city. from January 2010 to January 2018 were collected and retrospectively analyzed. The patients were divided into 2 groups: group A (152 patients with MRD-) and group B (58 patients with MRD+). The influencing factors of progression free survival and overall survival of patients were analyzed, and the correlation between MRD status and high-risk cytogenetic abnormalities, treatment plan and response to treatment were evaluated. RESULTS: There were no significant difference in clinical characteristics between the patients in 2 groups (P>0.05). Single factor analysis showed that ASCT and MRD status were related with progression free survival of patients with newly diagnosed MM (P<0.05). Multivariate analysis by Cox regression model showed that MRD+ persistence was the independent risk factor for progression free survival of patients with newly diagnosed MM (P<0.05). The cumulative progression free survival rate in 2-year with follow-up of patients in group A was significantly higher than that in B group (P<0.05). The median progression free survival time and overall survival time of patients with persistent MRD- were significantly longer than those of MRD+ (P<0.05). The single factor analysis showed that MRD- maintenance time was the influencing factor of PFS and OS time of newly diagnosed MM patients (P<0.05). The cumulative overall survival rate in 2-year with follow-up of patients with MRD- maintenance for 6 months was significantly higher than that of patients with MRD- maintenance for<6 months (P<0.05). The cumulative progression free survival rate and overall survival rate in 2 years with follow-up of patients with MRD- maintenance for ≥12 months were significantly higher than those of MRD-maintenance for <12 months(P<0.05). The median progression free survival time of patients with MRD- was significantly longer than that of patients with MRD+ who had≥ one kind of high-risk cytogenetic abnormality (P<0.05). The MRD- rate of patients received ASCT was significantly higher than that of patients without ASCT (P<0.05). The median progression free survival time of patients with MRD- was significantly longer than that of patients with MRD+ (P<0.05). The maintenance time of MRD- in patients with bortezomib treatment was significantly longer than that of patients without bortezomib treatment in population with MRD- (P<0.05). The median progression free survival time of patients with bortezomib treatment was significantly longer than patients without bortezomib treatment (P<0.05). CONCLUSION: MRD+ maintenance in newly diagnosed MM patients with VGPR and above after treatment closely relates with poor long-term prognosis, however, the MRD- maintenance time can be used for prognosis evaluation. MRD+ suggests that patients possess the possibility of early recurrence, and dynamic monitoring of MRD status in treatment can be helpful to clinical determination of treatment opportunity for relapsed MM patients.


Assuntos
Mieloma Múltiplo , Humanos , Neoplasia Residual , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1750-1756, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067985

RESUMO

OBJECTIVE: To investigate the safety and efficacy of tumor-associated antigen-specific cytotoxic T lympho- cytes (TAA-CTL) in the treatment of multiple myeloma (MM) and non-Hodgkin lymphoma (NHL). METHODS: Peripheral blood mononuclear cells (PBMNC)of patients were collected. Dendritic cells (DC) were loaded with multiple tumor-associated antigens (TAA) (NY-ESO-1, MAGE-A3, MAGE-A4, WT1, Survivin, PRAME, LMP1 and LMP2A), then co-cultured with PBMNC to induce cytotoxic T lymphocytes (CTL). The phenotypes of cell products were detected, and the disease statuse was evaluated in 7 patients during or after infusion. The changes of TAA-CTL amount in the PBMNC of patients were measured by using IFN-γ ELISpot assay. RESULTS: TAA-CTL products were generated comprising CD3+ T cells (mean 82.98%) with a mixture of CD4+ (mean 42.09%) and CD8+ (mean 25.32%) T cells. Among them, 70% expressed effectors memory markers (CD45RO+CD62L-CCR7-). Each patient received TAA-CTL infusions for 1-4 times, and none of them showed obvious adverse reactions. The clinical symptoms and laboratory or imaging examination of 5 patients achieved positive effects. After cell therapy, the spot-forming cells (SFC) levels of most patients gradually increased and the peak often appeared about 2-3 weeks after the infusion. CONCLUSION: TAA-CTLs preliminarily show its safety and efficacy in MM and NHL patients, however, a larger population sample is needed to explore its clinical application value.


Assuntos
Linfoma não Hodgkin , Mieloma Múltiplo , Células Dendríticas , Humanos , Leucócitos Mononucleares , Linfoma não Hodgkin/terapia , Mieloma Múltiplo/terapia , Linfócitos T Citotóxicos
12.
Blood Cancer J ; 10(10): 103, 2020 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-33077708

RESUMO

There is limited information on the characteristics, prognostic factors, and outcomes of patients with multiple myeloma (MM) hospitalized with COVID-19. This retrospective case series investigated 167 patients reported from 73 hospitals within the Spanish Myeloma Collaborative Group network in March and April, 2020. Outcomes were compared with 167 randomly selected, contemporary, age-/sex-matched noncancer patients with COVID-19 admitted at six participating hospitals. Among MM and noncancer patients, median age was 71 years, and 57% of patients were male; 75 and 77% of patients, respectively, had at least one comorbidity. COVID-19 clinical severity was moderate-severe in 77 and 89% of patients and critical in 8 and 4%, respectively. Supplemental oxygen was required by 47 and 55% of MM and noncancer patients, respectively, and 21%/9% vs 8%/6% required noninvasive/invasive ventilation. Inpatient mortality was 34 and 23% in MM and noncancer patients, respectively. Among MM patients, inpatient mortality was 41% in males, 42% in patients aged >65 years, 49% in patients with active/progressive MM at hospitalization, and 59% in patients with comorbid renal disease at hospitalization, which were independent prognostic factors on adjusted multivariate analysis. This case series demonstrates the increased risk and identifies predictors of inpatient mortality among MM patients hospitalized with COVID-19.


Assuntos
Infecções por Coronavirus/epidemiologia , Rim/patologia , Mieloma Múltiplo/epidemiologia , Pneumonia Viral/epidemiologia , Prognóstico , Idoso , Betacoronavirus/patogenicidade , Comorbidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Feminino , Hospitalização , Humanos , Pacientes Internados , Rim/efeitos dos fármacos , Rim/virologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/virologia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Índice de Gravidade de Doença
13.
Medicine (Baltimore) ; 99(43): e22952, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120856

RESUMO

Pulmonary hypertension (PH) is a complication of multiple myeloma (MM); however, the clinical outcomes and prognosis are relatively not well known. We aimed to investigate the risk factors of transthoracic echocardiography-defined PH and its impact on the clinical outcome in patients with MM.A retrospective study was performed using data from the Chonnam National University Hwasun Hospital database for patients who underwent transthoracic echocardiography (TTE) within 1 month of the MM diagnosis between January 2007 and December 2017. PH was defined as an estimated right ventricular systolic pressure (RVSP) > 40 mmHg. A total of 390 patients were included. TTE-defined PH was observed in 107 patients (27%). During the follow-up period (median, 688 days), all-cause death was noted for 134 patients (34.4%). In the Kaplan-Meier survival analysis, the cumulative overall survival and cardiovascular death-free survival rates were significantly lower in the PH group than in the non-PH group (P < .001). In the propensity score-matched population, RVSP > 40 mmHg on TTE and history of congestive heart failure (CHF) were identified as the significant independent predictors of all-cause and cardiovascular death.This study reports that the prevalence of TTE-defined PH is higher in patients with MM than in the general population. Moreover, TTE-defined PH and a history of CHF are the independent prognostic factors for all-cause and cardiovascular death in patients with MM. These results highlight the risk of associated cardiovascular disease in patients with MM and emphasize the importance of management strategies that prevent the deterioration of cardiac function.


Assuntos
Ecocardiografia/métodos , Hipertensão Pulmonar/etiologia , Mieloma Múltiplo/complicações , Mieloma Múltiplo/mortalidade , Idoso , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Estudos de Casos e Controles , Gerenciamento de Dados , Morte , Ecocardiografia/estatística & dados numéricos , Feminino , Insuficiência Cardíaca/epidemiologia , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Prognóstico , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Função Ventricular Direita/fisiologia
14.
Medicine (Baltimore) ; 99(44): e22931, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33126356

RESUMO

RATIONALE: Synchronous development of both anaplastic large cell lymphoma (ALCL) and multiple myeloma (MM) in a patient is rare. To our knowledge, until now only one case has been reported. Treatment needs to cover both and is a challenge. Here we reported another case and discussed the diagnosis and treatment. PATIENT CONCERNS: This is a 63-year old woman who presented with a mass in upper abdominal skin. Positron emission tomography/computed tomography (PET/CT) showed the high metabolism in left abdominal skin and left axillary lymph nodes. Histopathologic and immunohistochemical evaluation identified the cutaneous mass as an ALK-negative ALCL. Bone marrow smear showed increased plasma cells which expressed CD38, CD138, and cLambda concomitantly. The increased monoclonal immunoglobulin IgD λ was detected by immunofixation electrophoresis. DIAGNOSES: Diagnosis of both ALCL and MM was confirmed. INTERVENTIONS: The patient successively received 6 cycles of B-CHOD regimen, one cycle of ID regimen, 2 cycles of DHAX regimen, one cycle of L-DA-EPOCH and autologous stem cell transplantation (ASCT). Then lenalidomide was performed as a maintenance therapy. OUTCOMES: Both ALCL and MM achieved complete remission. LESSONS: We reported a very rare case with synchronous development of ALCL and MM, in whom a good therapeutic response to chemotherapies followed by ASCT has been observed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/métodos , Lenalidomida/administração & dosagem , Linfoma Anaplásico de Células Grandes , Mieloma Múltiplo , Neoplasias Cutâneas , Parede Abdominal/patologia , Bleomicina/administração & dosagem , Exame de Medula Óssea/métodos , Ciclofosfamida/administração & dosagem , Dexametasona/administração & dosagem , Doxorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Humanos , Imuno-Histoquímica , Linfoma Anaplásico de Células Grandes/imunologia , Linfoma Anaplásico de Células Grandes/patologia , Linfoma Anaplásico de Células Grandes/terapia , Quimioterapia de Manutenção/métodos , Pessoa de Meia-Idade , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/terapia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Prednisona/administração & dosagem , Indução de Remissão , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Transplante Autólogo/métodos , Vincristina/administração & dosagem
15.
Anticancer Res ; 40(10): 5727-5734, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988898

RESUMO

BACKGROUND/AIM: To examine the impact of ACA and the association of socioeconomic factors on delay in initial treatment for multiple myeloma (MM). PATIENTS AND METHODS: Patients diagnosed with MM between 2004-2016 were identified in the National Cancer Database (NCDB). Time-to-initial treatment (TTI) was defined as the number of days from diagnosis to initial therapy. Patients were classified into quartiles and those belonging to the fourth quartile for TTI constituted the delayed treatment group. Study period was divided into pre-ACA and post-ACA using 2010 as the cut-off. RESULTS: A total of 65,723 patients met the eligibility criteria. Median TTI was 13 (IQR=5-27) days. Racial-ethnic minorities were associated with delayed-TTI. Delayed treatment was more likely for Hispanics pre-ACA but not post-ACA, while non-Hispanic Blacks (NHB) were more likely to have delayed treatment both, pre- and post-ACA. CONCLUSION: While ACA has been shown to help mitigate healthcare disparities in certain cancer diagnoses, the study suggests that the effect is still limited among MM patients.


Assuntos
Disparidades em Assistência à Saúde/normas , Cobertura do Seguro/normas , Mieloma Múltiplo/epidemiologia , Patient Protection and Affordable Care Act , Idoso , Grupos de Populações Continentais , Grupos Étnicos , Grupo com Ancestrais do Continente Europeu , Feminino , Hispano-Americanos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Fatores Socioeconômicos , Estados Unidos/epidemiologia
16.
BMJ ; 370: m3176, 2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32958461

RESUMO

Despite considerable advances in treatment approaches in the past two decades, multiple myeloma remains an incurable disease. Treatments for myeloma continue to evolve with many emerging immunotherapies. The first immunotherapy used to treat hematologic cancers, including multiple myeloma, was an allogeneic stem cell transplant. In the mid-2000s, immunomodulatory drugs thalidomide, lenalidomide, and subsequently pomalidomide were proven to be effective in multiple myeloma and substantially improved survival. The next wave of immunotherapies for multiple myeloma included the monoclonal antibodies daratumumab and elotuzumab, which were approved by the Food and Drug Administration in 2015. Subsequently, a variety of immunotherapies have been developed for multiple myeloma, including chimeric antigen receptor T cells, bispecific antibodies, antibody drug conjugates, and checkpoint inhibitors. Many of these emerging treatments target the B cell maturation antigen, which is expressed on plasma cells, although several other novel receptors are also being studied. This review summarizes the evidence of these various immunotherapies, their mechanism of action, and data from clinical trials regarding the treatments' safety and efficacy.


Assuntos
Imunoterapia , Mieloma Múltiplo/terapia , Drogas em Investigação/uso terapêutico , Humanos , Fatores Imunológicos/uso terapêutico , Transplante de Células-Tronco
17.
Ann Hematol ; 99(10): 2351-2356, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32865607

RESUMO

Lenalidomide (Len) and dexamethasone (dex) therapy is a standard therapy in patients with multiple myeloma. Elderly or unfit patients may reduce Len or dex doses to prevent toxicities that lead to treatment discontinuation. However, there have been few studies evaluating the efficacy and safety of lower doses of Len and dex. We conducted a phase II study of 1.5-year low-dose Len and dex therapy following melphalan and prednisolone (MP), the number of which cycles was determined by a response within 9 cycles. The Len dose was 10 mg daily and the dex dose was 20 mg weekly, which were continued for 1.5 years. Twenty-one patients were enrolled. The median number of cycles of MP was 3 (range, 2-9). The overall response rate was 81% and a very good partial response or better was achieved in 33.3% of patients. The median follow-up time for survivors was 70.5 months (range, 42-83 months), the median progression-free survival (PFS) was 27 months (95% CI, 21-33 months), and the median overall survival was not reached. Grade 3 or 4 adverse events were observed in 28.6% of patients. In conclusion, the low-dose Len and dex therapy safely achieved comparable efficacies to the standard-dose regimen in elderly patients with newly diagnosed multiple myeloma. UMIN000007889.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anemia/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Relação Dose-Resposta a Droga , Esquema de Medicação , Neutropenia Febril/induzido quimicamente , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Lenalidomida/administração & dosagem , Lenalidomida/efeitos adversos , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Mieloma Múltiplo/genética , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Intervalo Livre de Progressão , Indução de Remissão , Resultado do Tratamento , Adulto Jovem
18.
Zhonghua Xue Ye Xue Za Zhi ; 41(8): 675-679, 2020 Aug 14.
Artigo em Chinês | MEDLINE | ID: mdl-32942823

RESUMO

Objective: In this study, we aimed to determine the change and clinical significance of serum level Apo A1 in MM patients. Methods: In total, 412 multiple myeloma patients were examined. SPSS 22.0 was used for data analysis. Correlation analysis was performed using linear correlation or Spearman rank correlation coefficients. Measurement data were analyzed with the t-test, Mann-Whitney U-test, or oneway analysis of variance (ANOVA) . Used the ROC curve to calculate the cutoff value and compared the OS and PFS between high Apo A1 subgroup and low Apo A1 subgroup with Kaplan-Meier survival analysis. Results: Our study showed that value of Apo A1 in the patient group was lower than that in the control group (0.89 g/L vs 1.24 g/L, P<0.05) . We found that Apo A1 dynamically changed with different MM stages. As it was increased when the disease was in remission, and decreased after disease in progression. According the result of multivariate analysis Apo A1 reduction become the independent risk factors of MM. On the basis of Kaplan-Meier survival analysis between high Apo A1 subgroup and low Apo A1 subgroup, we found higher Apo A1 patienta had longer OS rate and PFS. Conclusions: Apo A1 is a useful biomarker of tumor burden and a prognostic factor of multiple myeloma.


Assuntos
Mieloma Múltiplo , Apolipoproteína A-I , Biomarcadores , Humanos , Prognóstico , Curva ROC
19.
Anticancer Res ; 40(10): 5437-5443, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988865

RESUMO

BACKGROUND: Neuropilin-1 (NRP1) is a receptor for vascular endothelial growth factor A (VEGFA), and has been reported to be overexpressed in several malignancies. Since angiogenesis plays an important role in pathogenesis of multiple myeloma (MM) and the role of NRP1 in MM has not been studied yet, we characterized the expression of NRP1 in this disease. MATERIALS AND METHODS: The expression level of NRP1 was measured in 140 patients newly diagnosed with MM and 28 healthy controls by flow cytometry and quantitative reverse transcriptase polymerase chain reaction. RESULTS: Expression of NRP1 was significantly reduced on plasma cells (median=2.05%) compared to that on B-cells (median=10.05%, p<0.0001) in bone marrow of patients with MM. In MM, the expression of NRP1 was high on plasmacytoid dendritic cells (median=85.85%) and low on regulatory T-cells (median=0.6%). CONCLUSION: In MM, NRP1 is regulated differentially as compared to other B-cell malignancies at both the RNA and protein level.


Assuntos
Mieloma Múltiplo/genética , Neovascularização Patológica/genética , Neuropilina-1/genética , Fator A de Crescimento do Endotélio Vascular/genética , Adulto , Linfócitos B/metabolismo , Feminino , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/patologia , Neovascularização Patológica/sangue , Neovascularização Patológica/patologia , Neuropilina-1/sangue , Transdução de Sinais/genética
20.
Anticancer Res ; 40(9): 4979-4987, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878786

RESUMO

BACKGROUND/AIM: Multiple myeloma is a highly heterogeneous disease of clonal plasma cells. Histone deacetylase (HDAC) inhibitors are promising anticancer drugs but their precise mechanisms of actions are not well understood. MATERIALS AND METHODS: Cell-cycle regulation and pro-apoptotic effects of two histone deacetylase inhibitors, suberohydroxamic acid (SAHA) and suberoylanilide hydroxamic acid (SBHA), were analyzed in multiple myeloma cell lines RPMI8226 and U266 with differing TP53 status using gene-expression analysis. RESULTS: Enhanced expression of cyclin-dependent kinase inhibitor 1A (CDKN1A/p21WAF/CIP1) detected in the TP53-deleted U266 cell line after SAHA treatment indicates the P53-independent mode of transcriptional activation of CDKN1A gene. In contrast, CDKN1A gene expression was significantly increased by both SBHA and SAHA treatment of TP53-mutated RPMI8226 cells. CONCLUSION: SAHA appears to be a potentially effective pro-apoptotic and anticancer drug with universal application in the treatment of heterogeneous populations of multiple myeloma cells.


Assuntos
Inibidor de Quinase Dependente de Ciclina p21/genética , Mieloma Múltiplo/patologia , Proteína Supressora de Tumor p53/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p21/antagonistas & inibidores , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Humanos , Ácidos Hidroxâmicos/farmacologia , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Mieloma Múltiplo/metabolismo , Proteína Supressora de Tumor p53/genética
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