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1.
Clin Biochem ; 74: 42-46, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31526775

RESUMO

OBJECTIVES: Clinical decisions in patients with monoclonal gammopathies may be highly imprecise because of variations of parameters used in diagnosis. In this study, we aimed to calculate the variation in M-protein, free light chains (FLCs), and immunoglobulins in respective patients. DESIGN & METHODS: We analyzed the data of clinically stable patients with monoclonal gammopathy (MG), which were monitored for 7-years to determine the biological variations and reference change values (RCV) of serum M-protein, monoclonal serum FLCs and immunoglobulin (Ig) concentrations. Patients that were included in the study had no change in diagnosis and showed <5 g/L change in serum M-protein during the monitoring. From the patients included at least 3 consecutive samples were analyzed within 8 months and 7 years of initial diagnosis. RESULTS: The total coefficient of variations (CV) was calculated for M-protein and involved/uninvolved fractions of FLCs and immunoglobulins. From 38 patients and 456 samples that were included in the study, the total CVs were calculated for serial M-proteins (8.9%), serum involved FLCs (iFLC, 21.4%), involved Ig (i-Ig, 8.7%) and uninvolved Ig (u-Ig, 9.1%). Combining these CVs and the interassay analytical CVs, we calculated the biological CV for the serum M-protein (8.4%), serum iFLC concentration (21.1%), i-Ig (8.6%) and u-Ig (9.0%). A significant correlation was found in multiple myeloma patients between the κ/λ light chain ratio (rFLC) with i-Ig, the difference between i-Ig level and u-Ig level (d-Ig) and ratio Ig (r-Ig) (r = 0.790, 0.703 and 0.711, respectively). These correlations were not found in patients suffering from MG of undetermined significance and smoldering multiple myeloma. CONCLUSIONS: i-Ig determinations may be an alternative to M-protein for MGs. The variations in serum FLC measurements during MG monitoring were greater than those observed in serum M-proteins and therefore need to be more rigorously revised for recommendations.


Assuntos
Isotipos de Imunoglobulinas/sangue , Cadeias kappa de Imunoglobulina/sangue , Cadeias lambda de Imunoglobulina/sangue , Imunoglobulinas/sangue , Gamopatia Monoclonal de Significância Indeterminada/sangue , Mieloma Múltiplo/sangue , Mieloma Múltiplo Latente/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Estudos Retrospectivos
2.
Br J Hosp Med (Lond) ; 80(2): 91-98, 2019 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-30746991

RESUMO

Myeloma outcomes have improved dramatically over the last decade as a result of novel therapies, several of which are now commonly continued to disease relapse. Physicians who do not work in haematology are therefore more likely than ever before to be consulted by a patient with myeloma, either for an unrelated condition or with a side effect of myeloma or its treatment. Myeloma is also the cancer most likely to be diagnosed in accident and emergency departments or by the acute physician and so an awareness of its presentation and management is especially important in these settings to enable early diagnosis and limit the morbidity associated with end organ damage. This review summarizes the presenting features of disease, diagnostic criteria for myeloma and related plasma cell disorders, and discusses current management.


Assuntos
Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo Latente/diagnóstico , Doença Aguda , Lesão Renal Aguda/etiologia , Anemia/etiologia , Biópsia , Medula Óssea/patologia , Progressão da Doença , Serviço Hospitalar de Emergência , Fraturas Espontâneas/etiologia , Humanos , Hipercalcemia/etiologia , Gamopatia Monoclonal de Significância Indeterminada/sangue , Mieloma Múltiplo/sangue , Mieloma Múltiplo/complicações , Mieloma Múltiplo/terapia , Dor Musculoesquelética/etiologia , Mieloma Múltiplo Latente/sangue
3.
Nat Med ; 24(12): 1867-1876, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30523328

RESUMO

Multiple myeloma, a plasma cell malignancy, is the second most common blood cancer. Despite extensive research, disease heterogeneity is poorly characterized, hampering efforts for early diagnosis and improved treatments. Here, we apply single cell RNA sequencing to study the heterogeneity of 40 individuals along the multiple myeloma progression spectrum, including 11 healthy controls, demonstrating high interindividual variability that can be explained by expression of known multiple myeloma drivers and additional putative factors. We identify extensive subclonal structures for 10 of 29 individuals with multiple myeloma. In asymptomatic individuals with early disease and in those with minimal residual disease post-treatment, we detect rare tumor plasma cells with molecular characteristics similar to those of active myeloma, with possible implications for personalized therapies. Single cell analysis of rare circulating tumor cells allows for accurate liquid biopsy and detection of malignant plasma cells, which reflect bone marrow disease. Our work establishes single cell RNA sequencing for dissecting blood malignancies and devising detailed molecular characterization of tumor cells in symptomatic and asymptomatic patients.


Assuntos
Heterogeneidade Genética , Mieloma Múltiplo/sangue , Neoplasia Residual/sangue , Mieloma Múltiplo Latente/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Neoplasia Residual/genética , Neoplasia Residual/patologia , Mieloma Múltiplo Latente/genética , Mieloma Múltiplo Latente/patologia
5.
Clin Chim Acta ; 487: 306-308, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30315756

RESUMO

BACKGROUND: Pseudohyperphosphatemia is a rare laboratory finding in MM, especially in patients with smoldering myeloma (SMM) progressing to symptomatic multiple myeloma (MM). Laboratorians and clinicians should be aware of this phenomenon and take necessary actions to avoid misdiagnosis. METHODS: Specimens from a monoclonal IgG kappa SMM patient with extremely high serum phosphorus concentrations measured by the Roche phosphomolybdate assay were re-evaluated using serial dilutions and the ORTHO VITROS assay free from monoclonal gammaglobulin interference. Serum free kappa/lambda chain ratio was also assessed. RESULTS: Both serial dilutions and the ORTHO VITROS assay normalized serum phosphorus concentrations, suggesting the extremely high serum phosphorus concentrations measured by the Roche assay is due to interference from monoclonal gammaglobulin. Additionally, the patient's serum free kappa/lambda ratio was >100. Based on serum free kappa/lambda ratio, disease progression from SMM to MM was diagnosed. CONCLUSIONS: Prompt and appropriate laboratory investigations ensure correct diagnosis of pseudohyperphosphatemia and help clinicians properly manage patients. To our knowledge, this patient is the first reported case of pseudohyperphosphatemia in patients with progression from SMM to MM.


Assuntos
Mieloma Múltiplo/sangue , Mieloma Múltiplo Latente/sangue , Feminino , Humanos , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Fósforo/sangue , Mieloma Múltiplo Latente/patologia , gama-Globulinas/análise
6.
Anticancer Res ; 38(9): 5087-5092, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30194153

RESUMO

BACKGROUND/AIM: Monoclonal gammopathy of unknown significance (MGUS) and smoldering multiple myeloma often precede multiple myeloma (MM). The identification of biomarkers predicting progression to MM might facilitate an earlier diagnosis of MM. Our study assessed the diagnostic value of plasma levels of endocan, a 50-kDa soluble dermatan sulfate proteoglycan produced and secreted by endothelial cells, hitherto unknown in MM, in patients with plasma cell dyscrasia. MATERIALS AND METHODS: Endocan levels were determined in 96 peripheral blood plasma samples by sandwich enzyme-linked immunosorbent assay (ELISA) in healthy controls (n=12), in patients with MGUS (n=17), and in patients newly diagnosed with (n=42) or relapsed/refractory (n=25) MM. RESULTS: Median endocan concentration increased from MGUS (315.00 pg/ml) and healthy controls (316.19 pg/ml) to newly-diagnosed MM (371.82 pg/ml; p=0.027). The low endocan levels (median=246.20 pg/ml) in patients with relapsed/refractory MM were similar to those in healthy controls and patients with MGUS. A cut-off value of >220 pg/ml endocan in peripheral blood discriminated patients newly diagnosed with MM from those with MGUS (area under the curve(AUC)=0.66, 95% confidence interval(CI)=0.55-0.81). CONCLUSION: The plasma levels of endocan can non-invasively differentiate patients newly diagnosed with MM from those with MGUS and should therefore be evaluated prospectively as a potential diagnostic marker.


Assuntos
Gamopatia Monoclonal de Significância Indeterminada/metabolismo , Mieloma Múltiplo/metabolismo , Proteínas de Neoplasias/sangue , Proteoglicanas/sangue , Mieloma Múltiplo Latente/metabolismo , Regulação para Cima , Idoso , Biomarcadores Tumorais/sangue , Diagnóstico Diferencial , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gamopatia Monoclonal de Significância Indeterminada/sangue , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Mieloma Múltiplo/sangue , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo Latente/sangue , Mieloma Múltiplo Latente/diagnóstico
7.
Blood Cancer J ; 8(6): 59, 2018 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-29895887

RESUMO

In 2014, the International Myeloma Working Group reclassified patients with smoldering multiple myeloma (SMM) and bone marrow-plasma cell percentage (BMPC%) ≥ 60%, or serum free light chain ratio (FLCr) ≥ 100 or >1 focal lesion on magnetic resonance imaging as multiple myeloma (MM). Predictors of progression in patients currently classified as SMM are not known. We identified 421 patients with SMM, diagnosed between 2003 and 2015. The median time to progression (TTP) was 57 months (CI, 45-72). BMPC% > 20% [hazard ratio (HR): 2.28 (CI, 1.63-3.20); p < 0.0001]; M-protein > 2g/dL [HR: 1.56 (CI, 1.11-2.20); p = 0.01], and FLCr > 20 [HR: 2.13 (CI, 1.55-2.93); p < 0.0001] independently predicted shorter TTP in multivariate analysis. Age and immunoparesis were not significant. We stratified patients into three groups: low risk (none of the three risk factors; n = 143); intermediate risk (one of the three risk factors; n = 121); and high risk (≥2 of the three risk factors; n = 153). The median TTP for low-, intermediate-, and high-risk groups were 110, 68, and 29 months, respectively (p < 0.0001). BMPC% > 20%, M-protein > 2 g/dL, and FLCr > 20 at diagnosis can be used to risk stratify patients with SMM. Patients with high-risk SMM need close follow-up and are candidates for clinical trials aiming to prevent progression.


Assuntos
Guias de Prática Clínica como Assunto , Mieloma Múltiplo Latente/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Medula Óssea/patologia , Progressão da Doença , Feminino , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Proteínas do Mieloma , Razão de Chances , Guias de Prática Clínica como Assunto/normas , Prognóstico , Fatores de Risco , Mieloma Múltiplo Latente/sangue , Mieloma Múltiplo Latente/mortalidade
8.
Br J Haematol ; 182(4): 495-503, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29808907

RESUMO

Smouldering multiple myeloma (SMM) is associated with increased risk of progression to multiple myeloma within 2 years, with no approved treatments. Elotuzumab has been shown to promote natural killer (NK) cell stimulation and antibody-dependent cellular cytotoxicity (ADCC) in vitro. CD56dim (CD56dim /CD16+ /CD3- /CD45+ ) NK cells represent the primary subset responsible for elotuzumab-induced ADCC. In this phase II, non-randomized study (NCT01441973), patients with SMM received elotuzumab 20 mg/kg intravenously (cycle 1: days 1, 8; monthly thereafter) or 10 mg/kg (cycles 1, 2: weekly; every 2 weeks thereafter). The primary endpoint was the relationship between baseline proportion of bone marrow-derived CD56dim NK cells and maximal M protein reduction; secondary endpoints included overall response rate (ORR) and progression-free survival (PFS). Fifteen patients received 20 mg/kg and 16 received 10 mg/kg; combined data arepresented. At database lock (DBL, September 2014), no association was found between baseline CD56dim NK cell proportion and maximal M protein reduction. With minimum 28 months' follow-up (DBL: January 2016), ORR (90% CI) was 10% (2·7-23·2) and 2-year PFS rate was 69% (52-81%). Upper respiratory tract infections occurred in 18/31 (58%) patients. Four (13%) patients experienced infusion reactions, all grade 1-2. Elotuzumab plus lenalidomide/dexamethasone is under investigation for SMM.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Mieloma Múltiplo Latente , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Citotoxicidade Celular Dependente de Anticorpos/efeitos dos fármacos , Antígenos CD/sangue , Antígenos CD/imunologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Lenalidomida/administração & dosagem , Lenalidomida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/sangue , Proteínas de Neoplasias/imunologia , Mieloma Múltiplo Latente/sangue , Mieloma Múltiplo Latente/tratamento farmacológico , Mieloma Múltiplo Latente/imunologia , Mieloma Múltiplo Latente/mortalidade , Taxa de Sobrevida
11.
Leukemia ; 32(6): 1427-1434, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29463830

RESUMO

Smoldering multiple myeloma (SMM) is a biologically heterogeneous, clinically defined entity with a variable rate of progression to symptomatic multiple myeloma (MM). Reliable markers for progression are critical for the development of potential therapeutic interventions. We retrospectively evaluated the predictive value of the evolving pattern of serum M-protein among other progression risk factors in 206 patients with SMM diagnosed between 1973 and 2012. Median time from recognition of evolving type to progression into symptomatic MM was 1.1 years (95% CI 0.5-2.0) and progression rate at 3 years was 71%. Development of the evolving type drastically worsened the prognostic estimation made at diagnosis for every covariate predictive of progression (serum M-protein size, bone marrow plasma cell infiltration, immunoparesis and Mayo Clinic risk). On average, the hazard ratio for progression to symptomatic MM increased to 5.1 (95% CI 3.4-7.6) after recognition of the evolving type. In conclusion, in patients with SMM the evolving pattern accurately predicts the risk of early progression to symptomatic disease, thereby allowing the identification of ultra-high risk patients who would be candidates for immediate therapy.


Assuntos
Proteínas do Mieloma/análise , Mieloma Múltiplo Latente/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Mieloma Múltiplo Latente/mortalidade
12.
Integr Biol (Camb) ; 10(2): 82-91, 2018 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-29372735

RESUMO

Blood samples from patients with plasma cell disorders were analysed for the presence of circulating plasma cells (CPCs) using a microfluidic device modified with monoclonal anti-CD138 antibodies. CPCs were immuno-phenotyped using a CD38/CD56/CD45 panel and identified in 78% of patients with monoclonal gammopathy of undetermined significance (MGUS), all patients with smouldering and symptomatic multiple myeloma (MM), and none in the controls. The burden of CPCs was higher in patients with symptomatic MM compared with MGUS and smouldering MM (p < 0.05). FISH analysis revealed the presence of chromosome 13 deletions in CPCs that correlated with bone marrow results. Point mutations in KRAS were identified, including different mutations from sub-clones derived from the same patient. The microfluidic assay represents a highly sensitive method for enumerating CPCs and allows for the cytogenetic and molecular characterization of CPCs.


Assuntos
Dispositivos Lab-On-A-Chip , Gamopatia Monoclonal de Significância Indeterminada/sangue , Mieloma Múltiplo/sangue , Plasmócitos/patologia , Mieloma Múltiplo Latente/sangue , Anticorpos Monoclonais , Separação Celular/instrumentação , Separação Celular/métodos , Células Clonais/patologia , Desenho de Equipamento , Humanos , Hibridização in Situ Fluorescente , Microfluídica/métodos , Gamopatia Monoclonal de Significância Indeterminada/genética , Gamopatia Monoclonal de Significância Indeterminada/imunologia , Mieloma Múltiplo/genética , Mieloma Múltiplo/imunologia , Mutação , Plasmócitos/imunologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Mieloma Múltiplo Latente/genética , Mieloma Múltiplo Latente/imunologia , Sindecana-1/sangue
13.
Clin Biochem ; 51: 38-47, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28479151

RESUMO

Monoclonal gammopathies (MG) are defined by increased proliferation of clonal plasma cells, resulting in a detectable abnormality called monoclonal component or M-protein. Detection of the M-protein as either narrow peaks on protein electrophoresis and discrete bands on immunofixation is the defining feature of MG. MG are classified as low-tumor burden disorders, pre-malignancies and malignancies. Since significant disease can be present at any level, several different tests are employed in order to encompass the inherent diverse nature of the M-proteins. In this review, we discuss the main characteristics and limitations of clinical assays to detect M-proteins: protein electrophoresis, immunofixation, immunoglobulin quantitation, serum free light chains and heavy-light chain assays, as well as the newly developed MALDI-TOF mass spectrometric methods. In addition, the definitions of the pre-malignancies monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM), as well as monoclonal gammopathy of renal significance (MGRS) are presented in the context of the 2014 international guidelines for definition of myeloma requiring treatment, and the role of the laboratory in test selection for screening and monitoring these conditions is highlighted.


Assuntos
Técnicas de Laboratório Clínico , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Mieloma Múltiplo Latente/diagnóstico , Humanos , Imunoglobulinas/sangue , Gamopatia Monoclonal de Significância Indeterminada/sangue , Mieloma Múltiplo Latente/sangue
14.
Wiad Lek ; 70(6 pt 2): 1170-1174, 2017.
Artigo em Polonês | MEDLINE | ID: mdl-29533907

RESUMO

The monoclonal gammopathies are defined as heterogenous group of diseases characterized by proliferation of a single clone of plasma cells, producing immunoglobulin or light (rarely heavy) chains, which can be detected in blood or urine as monoclonal (M) protein. The most common among them is monoclonal gammopathy of undetermined significance (MGUS), the asymptomatic benign disorder, present in ~ 3% of the population aged ≥50 years. However MGUS is a pre malignant condition and may progress to symptomatic multiple myeloma or related malignancies, with annual rate of approximately 1%. The clone may also produce kidney damage, resulting from just the protein M, with different patterns of renal disease. Since the lesions are progressive and may be severe leading to a significant morbidity the term "monoclonal gammopathy of renal significance (MGRS)" has been recently introduced.


Assuntos
Transformação Celular Neoplásica , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Idoso , Diagnóstico Diferencial , Progressão da Doença , Feminino , Humanos , Imunoglobulinas/sangue , Masculino , Pessoa de Meia-Idade , Gamopatia Monoclonal de Significância Indeterminada/sangue , Gamopatia Monoclonal de Significância Indeterminada/urina , Mieloma Múltiplo Latente/sangue
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