RESUMEN
BACKGROUND: Immunofixation electrophoresis (IFE) is the standard method for confirming the presence of a monoclonal protein (M-protein) at multiple myeloma (MM) diagnosis. IFE is also essential at assessment of complete response (CR) and stringent CR during treatment. As the CR assessment is influenced by daratumumab and isatuximab, HYDRASHIFT assays were developed. METHODS: Samples from patients under treatment that included daratumumab or isatuximab were tested and monitored by IFE on the HYDRASYS system using HYDRASHIFT assays (HYDRASYS/HYDRASHIFT) and by IFE on the Epalyzer2 system (Epalyzer). RESULTS: The IFE using HYDRASYS/HYDRASHIFT avoided a false positive caused by drug-related IgG-κ and contributed to accurate assessment of CR. Furthermore, HYDRASYS/HYDRASHIFT detected small M-proteins at early relapse and detected free light chains (FLCs) in patients with renal impairment exhibiting high serum FLCs despite being often missed on Epalyzer. CONCLUSION: Sensitivity and specificity of M-protein detection vary greatly depending on the IFE system and reagents used.
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Anticuerpos Monoclonales Humanizados , Anticuerpos Monoclonales , Mieloma Múltiple , Proteínas de Mieloma , Humanos , Anticuerpos Monoclonales/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/sangre , Anticuerpos Monoclonales Humanizados/uso terapéutico , Proteínas de Mieloma/análisis , Femenino , Anciano , Masculino , Persona de Mediana Edad , Inmunoelectroforesis/métodos , Resultado del Tratamiento , Inmunoglobulina G/sangre , Cadenas kappa de Inmunoglobulina/sangre , Indicadores y ReactivosRESUMEN
Current guidelines recommend screening with serum M-protein and serum-free light chain analysis (S-FLC) when an M-protein-related disorder is suspected. Many patients with multiple myeloma will be overlooked if only serum M-protein is measured. Despite this, the general practitioners in some areas of Denmark cannot order S-FLC. This review aims to disseminate knowledge of the S-FLC analysis, its applicability, and limitations in the diagnostic workup for suspected monoclonal gammopathies.
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Cadenas Ligeras de Inmunoglobulina , Mieloma Múltiple , Humanos , Cadenas Ligeras de Inmunoglobulina/sangre , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/sangre , Paraproteinemias/diagnóstico , Paraproteinemias/sangre , Proteínas de Mieloma/análisisRESUMEN
BACKGROUND: Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome is a rare plasma cell (PC) neoplasm with associated paraneoplastic syndrome. According to the current diagnostic criteria, peripheral polyneuropathy and monoclonal PC proliferative disorder represent two mandatory criteria. CASE PRESENTATION: We report a 54-year-old male with peripheral neuropathy of bilateral lower limbs, sclerotic bone lesions, elevated vascular endothelial growth factor (VEGF) levels, splenomegaly, extravascular volume overload, endocrinopathy, and skin hemangiomas. Of note, serum and urine protein electrophoresis (PEP) and immunofixation electrophoresis (IFE) of this patient indicated undetectable M-protein and the normal ratio of free light chains κ and λ (FLC-R (κ/λ)). No monoclonal PCs were found in bone marrow examinations or biopsy of diseased bones. However, his clinical manifestations matched most of the diagnostic criteria. After excluding other diseases that are easily confused with POEMS syndrome, the diagnosis of variant POEMS syndrome with undetectable M-protein was proposed. The patient obtained clinically significant improvement and elevated VEGF returned to normal after 6 months of treatment with lenalidomide plus dexamethasone. CONCLUSIONS: Monoclonal PC dyscrasia (M-protein) while being a mandatory criterion for POEMS syndrome is undetectable in a considerable amount of patients that otherwise demonstrate typical symptoms. Here, we reported a case of variant POEMS syndrome with featured clinical manifestations, elevated VEGF levels, and good response to therapies targeting PCs but no evidence of M-protein. Therefore, negative results in M-protein and monoclonal PCs aren't enough to reject the diagnosis of POEMS syndrome. It is imperative to recognize the variant form of POEMS syndrome.
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Síndrome POEMS , Humanos , Síndrome POEMS/diagnóstico , Síndrome POEMS/patología , Masculino , Persona de Mediana Edad , Lenalidomida/uso terapéutico , Talidomida/uso terapéutico , Talidomida/análogos & derivados , Factor A de Crecimiento Endotelial Vascular , Dexametasona/uso terapéutico , Resultado del Tratamiento , Proteínas de Mieloma/análisisRESUMEN
As no unified treatment protocol or evidence yet exists for plasmapheresis without plasma, this study explored the outcomes of using 4% human albumin (ALB) solution as a replacement solution in patients undergoing plasma exchange for multiple myeloma (MM) patients with acute kidney injury (AKI). This study was prospectively registered (ChiCTR2000030640 and NCT05251896). Bortezomib-based chemotherapy plus therapeutic plasmapheresis (TPP) with 4% human ALB solution was assessed for three years in patients with MM aged >18 years, with AKI according to the Kidney Disease Improving Global Outcomes criteria, and without previous renal impairment from other causes. The primary endpoints were changes in renal function over 18 weeks and survival outcomes at 36 months. The secondary endpoints were the incidence of adverse reactions and symptom improvement. Among the 119 patients included in the analysis, 108 experienced renal reactions. The M protein (absolute changes: median -12.12%, interquartile ranges (IQRs) -18.62 to -5.626) and creatine (median -46.91 µmol/L, IQR -64.70 to -29.12) levels decreased, whereas the estimated glomerular filtration rate (eGFR) increased (median 20.66 mL/(min·1.73 m2), IQR 16.03-25.29). Regarding patient survival, 68.1% and 35.3% of patients survived for >12 and >36 months, respectively. The three symptoms with the greatest relief were urine foam, poor appetite, and blurred vision. All 11 patients (7.6%) who experienced mild adverse reactions achieved remission. In conclusion, in MM patients with AKI, plasma-free plasmapheresis with 4% human ALB solution and bortezomib-based chemotherapy effectively alleviated light chain damage to kidney function while improving patient quality of life.
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Lesión Renal Aguda , Bortezomib , Tasa de Filtración Glomerular , Mieloma Múltiple , Plasmaféresis , Humanos , Mieloma Múltiple/complicaciones , Mieloma Múltiple/terapia , Lesión Renal Aguda/terapia , Lesión Renal Aguda/etiología , Plasmaféresis/métodos , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Anciano , Bortezomib/administración & dosificación , Bortezomib/uso terapéutico , Prueba de Estudio Conceptual , Albúmina Sérica Humana/análisis , Albúmina Sérica Humana/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Resultado del Tratamiento , Adulto , Terapia Combinada , Proteínas de MielomaRESUMEN
BACKGROUND: Isatuximab, an IgG-kappa (IgGκ) anti-cluster of differentiation 38 (CD38) monoclonal antibody approved for use in patients with relapsed or refractory multiple myeloma (MM), can potentially interfere with the visualization of endogenous monoclonal protein (M-protein) on standard immunofixation electrophoresis (IFE) and lead to inaccurate classification of a patient's response to therapy. The Hydrashift 2/4 isatuximab IFE assay (Hydrashift isatuximab assay) removes isatuximab interference from IFE. Using samples from patients enrolled in clinical trials of isatuximab-based therapy for MM, we demonstrate how the Hydrashift isatuximab assay improves the ability to detect residual M-protein and offer recommendations for when the assay is most useful. METHODS: Samples from 141 patients with a variety of known M-protein isotypes were selected and analyzed by standard IFE and the Hydrashift isatuximab assay. A positive control containing isatuximab was run on every standard IFE and Hydrashift gel. RESULTS: The Hydrashift isatuximab assay reliably shifted the migration of isatuximab in patient samples. Standard IFE was adequate for determining 104 patients' M-protein status, and the Hydrashift isatuximab assay confirmed these results. In samples from 37 patients with a history of IgGκ MM and a single IgGκ band visible on standard IFE near the isatuximab migration site, the Hydrashift isatuximab assay was able to separate isatuximab from endogenous M-protein, identifying residual M-protein in 17 samples and preventing false-positive interpretations of standard IFE in 20 samples. CONCLUSIONS: The Hydrashift isatuximab assay is most useful in patients with known IgGκ MM when a single IgGκ band appears near the isatuximab migration site on standard IFE during isatuximab-based therapy. CLINICALTRIALS.GOV REGISTRATION NUMBERS: NCT03275285 and NCT03319667.
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Anticuerpos Monoclonales Humanizados , Inmunoelectroforesis , Mieloma Múltiple , Proteínas de Mieloma , Humanos , Mieloma Múltiple/sangre , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/inmunología , Mieloma Múltiple/diagnóstico , Inmunoelectroforesis/métodos , Proteínas de Mieloma/análisis , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales/uso terapéuticoRESUMEN
OBJECTIVES: Multiple myeloma (MM) is a plasma cell malignancy characterized by a monoclonal expansion of plasma cells that secrete a characteristic M-protein. This M-protein is crucial for diagnosis and monitoring of MM in the blood of patients. Recent evidence has emerged suggesting that N-glycosylation of the M-protein variable (Fab) region contributes to M-protein pathogenicity, and that it is a risk factor for disease progression of plasma cell disorders. Current methodologies lack the specificity to provide a site-specific glycoprofile of the Fab regions of M-proteins. Here, we introduce a novel glycoproteogenomics method that allows detailed M-protein glycoprofiling by integrating patient specific Fab region sequences (genomics) with glycoprofiling by glycoproteomics. METHODS: Glycoproteogenomics was used for the detailed analysis of de novo N-glycosylation sites of M-proteins. First, Genomic analysis of the M-protein variable region was used to identify de novo N-glycosylation sites. Subsequently glycopeptide analysis with LC-MS/MS was used for detailed analysis of the M-protein glycan sites. RESULTS: Genomic analysis uncovered a more than two-fold increase in the Fab Light Chain N-glycosylation of M-proteins of patients with Multiple Myeloma compared to Fab Light Chain N-glycosylation of polyclonal antibodies from healthy individuals. Subsequent glycoproteogenomics analysis of 41 patients enrolled in the IFM 2009 clinical trial revealed that the majority of the Fab N-glycosylation sites were fully occupied with complex type glycans, distinguishable from Fc region glycans due to high levels of sialylation, fucosylation and bisecting structures. CONCLUSIONS: Together, glycoproteogenomics is a powerful tool to study de novo Fab N-glycosylation in plasma cell dyscrasias.
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Mieloma Múltiple , Humanos , Mieloma Múltiple/metabolismo , Mieloma Múltiple/genética , Mieloma Múltiple/diagnóstico , Glicosilación , Proteómica/métodos , Espectrometría de Masas en Tándem , Glicoproteínas/metabolismo , Cromatografía Liquida , Proteínas de Mieloma/metabolismo , Proteínas de Mieloma/análisisRESUMEN
INTRODUCTION: Stage classification is an important underpinning of management in patients with cancer and rests on a combination of three components-T for tumor extent, N for nodal involvement, and M for distant metastases. This article details the revision of the N and the M components of thymic epithelial tumors for the ninth edition of the TNM classification of malignant tumors proposed by the Thymic Domain of the International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee. METHODS: The N and M components of the eighth edition staging system were verified by a large international collaborative data source through a data-driven analysis. A total of 9147 cases were included for analysis, including 7662 thymomas, 1345 thymic carcinomas, and 140 neuroendocrine thymic tumors. RESULTS: Lymph node involvement rates were 1.5% in thymomas and 17.6% and 27.7% in thymic carcinomas and neuroendocrine thymic tumors, respectively. Rates of lymph node metastasis were increasingly higher in tumors with higher T stage and higher-grade histologic type. Survival analysis validated the differences in the N and M categories proposed in the eighth edition staging system. Good discrimination in overall survival was detected among pathologic (p)N and pM categories in patients with thymoma and thymic carcinoma. CONCLUSIONS: No changes are proposed from the eighth edition for the N and M components. The proposed stage classification will provide a useful tool for management of the disease among the global thymic community.
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Neoplasias Pulmonares , Neoplasias Glandulares y Epiteliales , Tumores Neuroendocrinos , Timoma , Neoplasias del Timo , Humanos , Estadificación de Neoplasias , Neoplasias Pulmonares/patología , Timoma/patología , Proteínas de Mieloma , Neoplasias del Timo/patología , Pronóstico , Neoplasias Glandulares y Epiteliales/patología , Tumores Neuroendocrinos/patologíaRESUMEN
BACKGROUND: To improve the early detection rate of multiple myeloma (MM), the M-protein screening system has been performed in the hospital population at Zhongshan Hospital Fudan University since 2014, with electrophoretic-based monoclonal immunoglobulin (M-protein) screening integrated into the blood biochemistry panel. This study updated 7-year follow-up findings of MM patients diagnosed by screening-driven and symptom-driven approaches. METHODS: The retrospective study compared the characteristics and outcomes of patients diagnosed through two patterns by reviewing the plasma cell disease database from January 2014 to October 2021. The screening-driven group included patients diagnosed through the screening system during workups of unrelated medical conditions or routine checkups. In contrast, patients who visited or were referred to the hematological department due to myeloma-related end-organ damage were categorized into the symptom-driven group. RESULTS: There were 3,110,218 serum protein electrophoresis (SPEP) tests performed during 7 years, with 1.95% (60,609) patients yielding positive SPEP results. Of 911 confirmed MM cases (excluding concurrent amyloidosis), 366 were assigned to the screening-driven group, while 545 were to the symptom-driven group. Compared to the symptom-driven group, the screening group had more IgG subtypes, earlier International Stage System stages, fewer disease-related symptoms, lower ECOG scores, less extramedullary disease, a lower percentage of bone marrow plasma cells, and a lower level of lactate dehydrogenase. Frontline response results of two groups were similar. Patients detected through screening had a significantly improved median progression-free survival (PFS) than the symptom-driven group (62.2 vs. 24.9 months, p < 0.001, HR: 2.12, 95% CIs: 1.69-2.65), with median follow-ups of 32.6 and 27.4 months. Furthermore, the median overall survival (OS) was significantly longer in patients of the screening group (not reached vs. 62.3 months, p < 0.001, HR: 2.49, 95% CIs: 1.81-3.41). After being adjusted for well-acknowledged myeloma prognostic factors, the screening-driven diagnostic pattern remained an independent prognostic factor indicating improved PFS and OS in MM patients. CONCLUSION: Routine M-protein screening for MM in the hospital population results in an earlier diagnosis and better patient outcomes.
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Detección Precoz del Cáncer , Mieloma Múltiple , Humanos , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/sangre , Mieloma Múltiple/mortalidad , Masculino , Femenino , Persona de Mediana Edad , China/epidemiología , Estudios Retrospectivos , Anciano , Detección Precoz del Cáncer/métodos , Proteínas de Mieloma/análisis , Proteínas de Mieloma/metabolismo , Electroforesis de las Proteínas Sanguíneas , Adulto , Estudios de Seguimiento , Tamizaje Masivo/métodosRESUMEN
ABSTRACT: Plasma cell myeloma (PCM) is a monoclonal gammopathy (MGM) characterized by proliferation of abnormal clone of plasma cells infiltrating the bone marrow with consequent end organ damage. The clonal plasma cells secrete a single clone of immunoglobulins (Ig) leading to presence of M-protein in the serum and/or urine. The M-protein is appreciated as a discrete band on serum protein electrophoresis (SPE) in the gamma globulin region, also called the M-band. Biclonal gammopathy (BGM) occurs due to neoplastic transformation of a plasma cell clone undergoing Ig class switching or due to an independent neoplastic transformation event yielding proliferation of unrelated plasma cell clones, therefore resulting in two distinct M-bands on SPE. It is, however, vital to distinguish a true BGM from an apparent one (MGM presenting with two distinct bands on SPE) so as to make an accurate diagnosis. Hereby, we report a case of a 61-year-old man, diagnosed with PCM and presenting with two discrete bands on SPE (simulating a BGM) which turned out to be monoclonal in nature.
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Mieloma Múltiple , Humanos , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/sangre , Mieloma Múltiple/patología , Masculino , Persona de Mediana Edad , Electroforesis de las Proteínas Sanguíneas/métodos , Células Plasmáticas/patología , Células Plasmáticas/metabolismo , Proteínas de Mieloma/análisis , Diagnóstico Diferencial , Paraproteinemias/diagnóstico , Paraproteinemias/sangreRESUMEN
INTRODUCTION: A TNM-based system for all types of thymic epithelial tumors was introduced in the eighth edition of the TNM classification of thoracic malignancies. The Thymic Domain of the Staging and Prognostic Factors Committee of the International Association for the Study of Lung Cancer, composed of multispecialty international experts, was charged to develop proposals for the ninth edition. This article outlines the proposed definitions for the T, the N, and the M components and their combination into stage groups. METHODS: A large central database of 11,347 patients with thymic epithelial tumors was assembled thanks to the contribution of the major thymic organizations worldwide and analyses were carried out for the T, the N, and the M components and the stage groups. Overall survival was the outcome measure for patients with completely and incompletely resected tumors, and recurrence for those with complete resection. When the number of patients was sufficient, analyses were performed separately for thymomas, thymic carcinomas, and neuroendocrine thymic tumors. RESULTS: Tumor size is included in the T1 category as T1a (≤5cm) and T1b (>5 cm); the mediastinal pleura is dropped as a T descriptor; invasion of the lung or phrenic nerve is reclassified as T2 (instead of T3). No changes are proposed for the N and the M components from the eighth edition. The stage groups remain the same. CONCLUSIONS: The proposed changes for the ninth edition of the TNM classification set the stage for further progress in the future for these rare tumors.
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Neoplasias Pulmonares , Neoplasias Glandulares y Epiteliales , Tumores Neuroendocrinos , Timoma , Neoplasias del Timo , Humanos , Estadificación de Neoplasias , Neoplasias Pulmonares/patología , Pronóstico , Proteínas de Mieloma , Neoplasias del Timo/patología , Timoma/patología , Tumores Neuroendocrinos/patología , Neoplasias Glandulares y Epiteliales/patologíaRESUMEN
Monoclonal gammopathy of undetermined significance (MGUS) is a plasma cell disorder that can precede the diagnosis of multiple myeloma. MGUS is characterized by the presence of a monoclonal paraprotein without evidence of multiple myeloma or other lymphoplasmacytic malignancies. Even though MGUS is an asymptomatic condition that does not require management strategies other than periodic follow-up to prevent complications, secondary nonmalignant diseases may arise, requiring control of the plasma cell clone. Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder that occurs in patients with no prior personal or family history of bleeding. It is associated with several other disorders, such as neoplasia, mainly hematological (including MGUS and other lymphoproliferative disorders), autoimmune, infectious and cardiac diseases. At diagnosis, patients usually present with cutaneous and mucosal bleeding, including gastrointestinal bleeding. Here, we report a case of a patient with MGUS who developed AVWS after one year of follow-up. The patient was refractory to glucocorticoids and cyclophosphamide and achieved remission only after monoclonal paraprotein was eradicated following treatment with bortezomib and dexamethasone. Our report sdemonstrates that, for refractory cases, eradication of the monoclonal paraprotein may be necessary to treat bleeding complications due to MGUS-associated AVWS.
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Gammopatía Monoclonal de Relevancia Indeterminada , Mieloma Múltiple , Paraproteinemias , Enfermedades de von Willebrand , Humanos , Gammopatía Monoclonal de Relevancia Indeterminada/complicaciones , Gammopatía Monoclonal de Relevancia Indeterminada/tratamiento farmacológico , Bortezomib/uso terapéutico , Mieloma Múltiple/complicaciones , Mieloma Múltiple/tratamiento farmacológico , Paraproteinemias/complicaciones , Paraproteinemias/tratamiento farmacológico , Enfermedades de von Willebrand/complicaciones , Enfermedades de von Willebrand/tratamiento farmacológico , Proteínas de MielomaRESUMEN
OBJECTIVES: Investigate the effect of tamoxifen on the occurrence of tooth loss (TL) in breast cancer (BC) survivors. METHODS: A cross-sectional study was conducted with 140 BC survivors using tamoxifen therapy. Sociodemographic, medical, and dental data were evaluated. TL was determined using the M component of the Decayed, Missing and Filled Teeth (DMFT) index. Logistic regression models were run to determine associations between the independent variables and outcome (TL). RESULTS: Mean TL was 12.96 (SD 8.88). Only three participants had lost no teeth and 10.7% were completely edentulous. Participants who used tamoxifen for more than 1 year had a higher mean missing teeth (13.99 vs. 10.45; P = 0.030). After the adjustments, the occurrence of more than 12 missing teeth was 2.75-fold higher among women who used tamoxifen for more than 1 year (95% CI: 1.06-7.12). Moreover, age over 65 years, referral for treatment by the public healthcare system, less use of dental services, xerostomia, and a lower occurrence of dental caries remained associated with the loss of more than 12 teeth. CONCLUSION: Longer use of tamoxifen was associated with greater tooth loss in breast cancer survivors. CLINICAL RELEVANCE: Based on estimates of the increase in cases of breast cancer, the prolonged use of tamoxifen for the treatment of this disease can exert an impact on oral health through the occurrence of tooth loss. These findings can contribute to the planning and implementation of oral health care and prevention strategies for such patients.
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Neoplasias de la Mama , Caries Dental , Pérdida de Diente , Anciano , Neoplasias de la Mama/tratamiento farmacológico , Estudios Transversales , Caries Dental/inducido químicamente , Caries Dental/epidemiología , Femenino , Humanos , Proteínas de Mieloma , Prevalencia , Tamoxifeno/efectos adversos , Pérdida de Diente/inducido químicamente , Pérdida de Diente/epidemiologíaRESUMEN
Objectives: To examine the influence of the proportion of pathological subtypes on the prognosis of stage â A lung adenocarcinoma cases, and to explore the association between the presence/absence of solid or micropapillary (S/M) components and survival outcome. Methods: Totally 321 patients with stage â A lung adenocarcinoma who received complete surgical resection at Department of Thoracic Surgery, Tongji University Affiliated Shanghai Pulmonary Hospital from January 2011 to December 2013 were retrospectively analyzed. There were 130 males and 191 females, aging 59(11) years (M(IQR)) (range: 55 to 66 years). The diagnostic value of the proportion of each pathological growth subtype on relapse-free survival (RFS) and overall survival (OS) were analyzed by using receiver operator characteristic curve. Patients were firstly divided into two groups according to the presence or absence of S/M components. And patients without S/M components were farther divided into two groups according to predominant growth pattern. There were three groups in total: with S/M components (group S/M+), without S/M components and lepidic growth pattern predominant (group S/M-LPA), without S/M components and papillary or acinar growth pattern predominant (group S/M-P/A). Kaplan-Meier method were used to draw the survival curves of the three groups, and Log-rank test were used to compare RFS and OS among the three groups. Cox proportional risk model was used to verify whether the presence of S/M components was a prognostic factor on RFS. Results: The proportion of S/M components had no diagnostic value for recurrence (solid: area under curve (AUC)=0.588, P=0.095; micropapillary: AUC=0.566, P=0.106) and death (AUC=0.589, P=0.104; AUC=0.607, P=0.056). The 5-year RFS rate of group S/M-LPA, S/M-P/A and S/M+ were 92.4%, 82.3% and 77.3%, respectively (all P<0.05), while the 5-year OS rate were 97.4%, 94.5% and 83.2%, respectively (all P<0.05). Multivariable analysis showed that the 3 groups were independent predictors of recurrence (S/M-P/A vs. S/M- LPA: HR=2.691, 95%CI: 1.249 to 5.799, P=0.011; S/M+ vs. S/M-LPA, HR=6.763, 95%CI: 3.050 to 14.996, P<0.01). Conclusions: The proportion of S/M components in stage â A lung adenocarcinoma with complete resection cases did not affect survival outcome. New grouping method based on the presence or absence of S/M components were significantly associated with patient survival outcomes: S/M+ patients had the worst prognosis and S/M-LPA patients had the best prognosis.
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Adenocarcinoma del Pulmón , Adenocarcinoma , Neoplasias Pulmonares , Adenocarcinoma/diagnóstico , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/cirugía , China , Femenino , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirugía , Masculino , Proteínas de Mieloma , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Pronóstico , Estudios RetrospectivosRESUMEN
OBJECTIVES: Myeloma is characterised by the presence of monoclonal immunoglobulin (M-protein) and the free light chain (FLC) in blood. We investigated whether these M-proteins and FLC are detectable in myeloma patients' saliva to evaluate its utility for non-invasive screening and monitoring of haematological malignancies. METHODS: A total of 57 patients with monoclonal gammopathy and 26 age-matched healthy participants provided paired serum and saliva samples for immunoglobulin characterisation and quantification. RESULTS: Myeloma patients had IgG or IgA M-protein levels ranging up to five times and FLC levels up to a thousand times normal levels of polyclonal immunoglobulins. Despite these highly elevated levels, only two IgG and no IgA M-proteins or FLC could be detected in paired saliva samples. Most patients had reduced levels of serum polyclonal immunoglobulins, but all had normal levels of salivary IgA. CONCLUSIONS: Immunoglobulin transfer from blood is not determined by levels in the systemic circulation and more likely dictated by periodontal inflammation and the integrity of the oral epithelium. Immunoglobulins secreted by bone marrow plasma cells do not substantially enter saliva, which represents a poor medium for myeloma diagnosis. These findings, along with normal salivary IgA levels despite systemic immunoparesis, support a strong partitioning of oral from systemic humoral immunity.
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Mieloma Múltiple , Proteínas de Mieloma , Humanos , Inmunoglobulina A , Inmunoglobulina G , Cadenas Ligeras de Inmunoglobulina , Inmunoglobulinas , Saliva/metabolismoRESUMEN
Monoclonal gammopathy (MG) is common in autoimmune diseases (AID), but its progression to hematological neoplasm (HN) and the predictors for the progression are unclear. Patients diagnosed with AID and MG in our hospital from January 2010 to June 2017 were reviewed and followed. Cox proportional hazard regression analysis was applied. Of 160 patients with AID and MG, the most common AID was primary SjÓ§gren's syndrome (37, 23.1%). Thirty-nine (24.4%) patients developed HN during follow-up (median: 3.7 years, IQR: 0.3-5.5 years). The cumulative probability of HN progression was 21.8% at one year and 29.3% at six years after the finding of MG. High levels of monoclonal protein (> 14.35% of total serum protein) (HR 11.71, 95%CI: 5.37-25.54), significant weight loss (HR 6.24, 95%CI: 2.87-13.59), and reduction of other types of immunoglobulins (HR 3.02, 95%CI: 1.40-6.48) are independent risk indicators for HN whose presence warrants vigorous follow-up and monitoring.
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Enfermedades Autoinmunes/complicaciones , Neoplasias Hematológicas/etiología , Paraproteinemias/complicaciones , Adulto , Anciano , Enfermedades Autoinmunes/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Proteínas de Mieloma/análisis , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Atención Terciaria de SaludRESUMEN
We retrospectively examined 57 patients with multiple myeloma who underwent autologous stem cell transplantation (ASCT) at our institution. A receiver-operating characteristic curve (ROC) analysis showed that the reduction rate of quantitative serum monoclonal protein (M-protein) before ASCT and the difference in involved and uninvolved free light chains (dFLC) 30 days after ASCT, respectively, had the greatest predictive value for all patients (area under the curve [AUC] 0.791 and 0.660, respectively). Based on the ROC curve-based cutoff values of tumor burden parameters, progression-free survival (PFS) in the high serum M-protein reduction (≥90 %) group was significantly better than that in the low serum M-protein reduction group (<90 %) (2-year PFS 79.5 % vs. 17.0 %, p < 0.001), but there were no significant differences in PFS between the low (<5.2 mg/L) and high (≥5.2 mg/L) dFLC groups (2-year PFS, 72.0 % vs. 46.0 %; p = 0.149). A multivariate analysis identified the reduction in serum M-protein as an independent predictive factor before ASCT for PFS (hazard ratio [HR] 0.287, p = 0.022) and high dFLC on day 30 after ASCT for PFS (HR 3.902, p = 0.040). These results demonstrate that a good prognosis can be expected with a reduction of serum M-protein before and after ASCT.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Mieloma Múltiple/terapia , Carga Tumoral , Adulto , Anciano , Femenino , Humanos , Cadenas Ligeras de Inmunoglobulina/metabolismo , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Mieloma Múltiple/patología , Proteínas de Mieloma/metabolismo , Evaluación de Resultado en la Atención de Salud/métodos , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Tiempo , Trasplante Autólogo , Adulto JovenRESUMEN
PURPOSE: Elotuzumab plus pomalidomide/dexamethasone (E-Pd) demonstrated efficacy and safety in relapsed and refractory multiple myeloma (RRMM). The clinical pharmacology of elotuzumab [± lenalidomide/dexamethasone (Ld)] was characterized previously. These analyses describe elotuzumab population pharmacokinetics (PPK), the effect of Pd, and assess elotuzumab exposure-response relationships for efficacy and safety in patients with RRMM. METHODS: A previously established PPK model was updated with E-Pd data from the phase 2 ELOQUENT-3 study (NCT02654132). The dataset included 8180 serum concentrations from 440 patients with RRMM from 5 clinical trials. Elotuzumab PK parameter estimates were used to generate individual daily time-varying average concentrations (daily Cavg) for multi-variable time-to-event exposure-response analyses of progression-free survival (PFS) and time to the first occurrence of grade 3 + adverse events (AEs) in RRMM. RESULTS: Elotuzumab PK were well-described by a two-compartment model with parallel linear and Michaelis-Menten elimination from the central compartment (Vmax) and non-renewable target-mediated elimination from the peripheral compartment (Kint). Co-administration with Pd resulted in a 19% and 51% decrease in elotuzumab linear clearance and Kint, respectively, versus Ld; steady-state exposures were similar. Vmax increased with increasing serum M-protein. Hazard ratios (95% confidence intervals) for daily Cavg were 0.9983 (0.9969-0.9997) and 0.9981 (0.9964-0.9998) for PFS and grade 3 + AEs, respectively. CONCLUSIONS: The PPK model adequately described the data and was appropriate for determining exposures for exposure-response analyses. There were no clinically relevant differences in elotuzumab exposures between Pd and Ld backbones. In ELOQUENT-3, increasing elotuzumab daily Cavg prolonged PFS without increasing grade 3 + AEs.
Asunto(s)
Anticuerpos Monoclonales Humanizados/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/sangre , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Dexametasona/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/sangre , Mieloma Múltiple/patología , Proteínas de Mieloma/análisis , Recurrencia Local de Neoplasia/tratamiento farmacológico , Supervivencia sin Progresión , Talidomida/administración & dosificación , Talidomida/análogos & derivados , Resultado del TratamientoAsunto(s)
Citometría de Flujo/métodos , Cadenas Ligeras de Inmunoglobulina/sangre , Mieloma Múltiple/sangre , Neoplasia Residual/sangre , Espectrometría de Masa por Ionización de Electrospray/métodos , Médula Ósea/metabolismo , Médula Ósea/patología , Cromatografía Liquida/métodos , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Quimioterapia de Inducción/métodos , Quimioterapia de Mantención/métodos , Espectrometría de Masas/métodos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/patología , Proteínas de Mieloma/análisis , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodosAsunto(s)
Crioglobulinemia/etiología , Mieloma Múltiple/complicaciones , Vasculitis/etiología , Anciano , Bortezomib/uso terapéutico , Dexametasona/uso terapéutico , Humanos , Inmunoglobulina G/análisis , Masculino , Proteínas de Mieloma/análisis , Recurrencia , Ombligo , Vasculitis/tratamiento farmacológicoRESUMEN
BACKGROUND: Plasma cell disorders (PCDs) are typically characterized by excessive production of a single immunoglobulin, defined as a monoclonal protein (M-protein). Some patients have more than one identifiable M-protein, termed biclonal. Traditional immunofixation electrophoresis (IFE) cannot distinguish if two bands of the same isotype represent biclonal proteins or M-proteins with some other feature. A novel assay using immunoenrichment coupled to matrix-assisted laser desorption ionization time-of-flight mass-spectrometry (Mass-Fix) was applied to determine whether two bands of the same isotype represented (1) monomers and dimers of a single M-protein, (2) an M-protein plus a therapeutic monoclonal antibody (t-mAb), (3) an M-protein with light chain glycosylation, or (4) two distinct biclonal M-proteins. METHODS: Patient samples with two bands of the same isotype identified by IFE were enriched using nanobodies against IgG, IgA, IgM, or κ and λ light chains then analyzed by Mass-Fix. Light chain masses were used to differentiate IgGκ M-proteins from t-mAbs. Mass differences between peaks were calculated to identify N-glycosylation or matrix adducts. High-resolution mass spectrometry was used as a comparator method in a subset of samples. RESULTS: Eighty-one residual samples were collected. For IgA, 93% (n = 25) were identified as monoclonal. For IgG, 67% (n = 24) were monoclonal, and 33% (n = 12) were truly biclonal. Among the monoclonal IgGs, the second band represented a glycosylated form for 21% (n = 5), while 33% (n = 8) had masses consistent with a t-mAb. 44% (n = 8) of IgM samples were biclonal, and 56% (n = 10) were monoclonal, of which one was glycosylated. CONCLUSIONS: We demonstrate the utility of mass spectrometry in the characterization of multiple IFE bands of the same isotype. Improved reporting accuracy of M-proteins is useful for monitoring of patients with PCDs.