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Smoldering myeloma

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https://www.readbyqxmd.com/read/28061989/high-risk-smoldering-myeloma-perspective-on-watchful-monitoring
#1
REVIEW
Siyang Leng, Suzanne Lentzsch
In a 2008 paper, Dispenzieri and colleagues at the Mayo Clinic proposed a risk stratification system for patients with smoldering multiple myeloma (SMM) based on the presence of three risk factors: serum M-protein ≥3 g/dL, bone marrow plasma cell percentage ≥10%, and a free light chain (FLC) ratio (κ to λ) of either ≤0.125 or ≥8. The patient in this vignette has all three risk factors, classifying him as high-risk, with an associated median time to progression (TTP) of 1.9 years. This is significantly worse than a patient with intermediate-risk (median TTP 5...
December 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/28061988/treatment-of-high-risk-smoldering-myeloma
#2
REVIEW
Neha Korde
Multiple myeloma (MM) is a hematologic malignancy of the plasma cell that causes symptoms of bone pain, renal failure, and anemia. It is usually preceded by a precursor disease state, such as smoldering multiple myeloma (SMM) or monoclonal gammopathy of undetermined significance (MGUS), and traditional dogma dictates that treatment should be initiated on frank MM symptom development. Emerging evidence suggests that a defined group of "high-risk SMM" may benefit from early treatment, before organ damage and symptoms actually occur...
December 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/28061984/controversies-in-multiple-myeloma-evidence-based-update
#3
REVIEW
Inhye E Ahn, Sham Mailankody
The US Food and Drug Administration (FDA) approved 10 new drugs for the treatment of multiple myeloma (MM) over the last two decades. The influx of new anti-myeloma agents with high efficacy and acceptable tolerability add complexity to the clinical decision-making process. First, treatment of smoldering multiple myeloma (SMM) remains investigational to date, although a randomized trial showed a survival gain in high-risk patients receiving lenalidomide. Second, in newly diagnosed MM, the majority of contemporary induction regimens have been studied in single-arm trials or compared to an older regimen, which complicates evidence-based treatment selection...
December 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/28057743/il21r-expressing-cd14-cd16-monocytes-expand-in-multiple-myeloma-patients-leading-to-increased-osteoclasts
#4
Marina Bolzoni, Domenica Ronchetti, Paola Storti, Gaetano Donofrio, Valentina Marchica, Federica Costa, Luca Agnelli, Denise Toscani, Rosanna Vescovini, Katia Todoerti, Sabrina Bonomini, Gabriella Sammarelli, Andrea Vecchi, Daniela Guasco, Fabrizio Accardi, Benedetta Dalla Palma, Barbara Gamberi, Carlo Ferrari, Antonino Neri, Franco Aversa, Nicola Giuliani
Bone marrow monocytes are primarily committed to osteoclast formation. It is, however, unknown whether potential primary alterations are specifically present in bone marrow monocytes of multiple myeloma patients, smoldering myeloma or monoclonal gammopathy of uncertain significance. Herein, we analyzed the immunophenotypic and transcriptional profiles of bone marrow CD14+ monocytes in a cohort of patients with different types of monoclonal gammopathies to identify alterations involved in myeloma-enhanced osteoclastogenesis...
January 5, 2017: Haematologica
https://www.readbyqxmd.com/read/27998645/thrombotic-microangiopathy-associated-with-monoclonal-gammopathy
#5
Aishwarya Ravindran, Ronald S Go, Fernando C Fervenza, Sanjeev Sethi
Thrombotic microangiopathy (TMA) is a rare disease comprising of a diverse set of disorders linked by a common histologic finding of endothelial injury. Monoclonal immunoglobulins may act as a potential trigger in the pathogenesis of TMA. To determine the prevalence of monoclonal gammopathy and clinicopathological features of TMA associated with monoclonal immunoglobulin, we performed a retrospective study in adults (18 and older) with a clinical diagnosis of TMA. Of 146 patients with TMA, we detected monoclonal immunoglobulin in 20 patients (13...
December 17, 2016: Kidney International
https://www.readbyqxmd.com/read/27983725/a-gene-expression-inflammatory-signature-specifically-predicts-multiple-myeloma-evolution-and-patients-survival
#6
C Botta, M T Di Martino, D Ciliberto, M Cucè, P Correale, M Rossi, P Tagliaferri, P Tassone
Multiple myeloma (MM) is closely dependent on cross-talk between malignant plasma cells and cellular components of the inflammatory/immunosuppressive bone marrow milieu, which promotes disease progression, drug resistance, neo-angiogenesis, bone destruction and immune-impairment. We investigated the relevance of inflammatory genes in predicting disease evolution and patient survival. A bioinformatics study by Ingenuity Pathway Analysis on gene expression profiling dataset of monoclonal gammopathy of undetermined significance, smoldering and symptomatic-MM, identified inflammatory and cytokine/chemokine pathways as the most progressively affected during disease evolution...
December 16, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27974705/are-neurological-complications-of-monoclonal-gammopathy-of-undetermined-significance-underestimated
#7
Normann Steiner, Angelika Schwärzler, Georg Göbel, Wolfgang Löscher, Julia Wanschitz, Eberhard Gunsilius
OBJECTIVES: Monoclonal gammopathy of undetermined significance (MGUS) is a premalignancy preceding multiple myeloma (MM) or related disorders. Neurological symptoms caused by the monoclonal immunoglobulins or free light-chains are often associated with a high morbidity. We analyzed the prevalence of neuropathy, clinical features and the long-term outcome in 223 patients (pts.) with MGUS. PATIENTS AND METHODS: Between 1/2005 and 3/2015, 223 adult pts. with MGUS were identified in our database...
December 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27936757/polyclonal-immunoglobulin-g-n-glycosylation-in-the-pathogenesis-of-plasma-cell-disorders
#8
Stefan Mittermayr, Giao N Lê, Colin Clarke, Silvia Millán Martín, Anne-Marie Larkin, Peter O'Gorman, Jonathan Bones
The pathological progression from benign monoclonal gammopathy of undetermined significance (MGUS) to smoldering myeloma (SMM) and finally to active myeloma (MM) is poorly understood. Abnormal immunoglobulin G (IgG) glycosylation in myeloma has been reported. Using a glycomic platform composed of hydrophilic interaction UPLC, exoglycosidase digestions, weak anion-exchange chromatography, and mass spectrometry, polyclonal IgG N-glycosylation profiles from 35 patients [MGUS (n = 8), SMM (n = 5), MM (n = 8), complete-response (CR) post-treatment (n = 5), relapse (n = 4), healthy age-matched control (n = 5)] were characterized to map glycan structures in distinct disease phases of multiple myeloma...
December 12, 2016: Journal of Proteome Research
https://www.readbyqxmd.com/read/27924175/serum-free-light-chain-assay-and-%C3%AE%C2%BA-%C3%AE-ratio-performance-in-patients-with-monoclonal-gammopathy-high-false-negative-rate-for-%C3%AE%C2%BA-%C3%AE-ratio
#9
Gurmukh Singh
BACKGROUND: Serum free light chain assay (SFLCA) and κ/λ ratio, and protein electrophoretic methods are used in the diagnosis and monitoring of monoclonal gammopathies. METHODS: Results for serum free light chains, serum and urine protein electrophoreses and immunofixation electrophoreses in 468 patients with a diagnosis of monoclonal gammopathy were compared. The results of the two methods were graded as concordant, non-concordant or discordant with the established diagnoses to assess the relative performance of the methods...
January 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/27822103/the-danish-national-multiple-myeloma-registry
#10
REVIEW
Peter Gimsing, Morten O Holmström, Tobias Wirenfelt Klausen, Niels Frost Andersen, Henrik Gregersen, Robert Schou Pedersen, Torben Plesner, Per Trøllund Pedersen, Mikael Frederiksen, Ulf Frølund, Carsten Helleberg, Annette Vangsted, Peter de Nully Brown, Niels Abildgaard
AIM: The Danish National Multiple Myeloma Registry (DMMR) is a population-based clinical quality database established in January 2005. The primary aim of the database is to ensure that diagnosis and treatment of plasma cell dyscrasia are of uniform quality throughout the country. Another aim is to support research. Patients are registered with their unique Danish personal identification number, and the combined use of DMMR, other Danish National registries, and the Danish National Cancer Biobank offers a unique platform for population-based translational research...
2016: Clinical Epidemiology
https://www.readbyqxmd.com/read/27804161/monoclonal-gammopathy-of-undetermined-significance-mgus-and-smoldering-myeloma-smm-a-practical-guide-to-management
#11
Nicola Maciocia, Ashutosh Wechalekar, Kwee Yong
Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma are precursor conditions of symptomatic multiple myeloma (MM). Diagnostic principles are aimed at excluding MM requiring therapy, other conditions associated with paraproteins that may require different management, and risk stratifying patients for the purposes of tailored follow-up and investigation. The International Myeloma Working Group have recently published a revised definition of MM, which singles out a small group of patients with smoldering multiple myeloma who are at very high risk of progression and organ damage; such patients are now included under the definition of MM and recommended to start anti-myeloma treatment...
November 2, 2016: Hematological Oncology
https://www.readbyqxmd.com/read/27796540/effects-of-elotuzumab-on-qt-interval-and-cardiac-safety-in-patients-with-multiple-myeloma
#12
Chaitali Passey, Raymond Darbenzio, Ying-Ming Jou, Mark Lynch, Manish Gupta
PURPOSE: To assess the effect of elotuzumab on corrected QT (QTc) intervals and cardiac safety. METHODS: Patients with high-risk smoldering multiple myeloma who had been treated with elotuzumab monotherapy (10 or 20 mg/kg) in Study CA204011 (NCT01441973) underwent electrocardiogram (ECG) examination over 8-10 weeks (treatment cycles 1-3). ECG intervals and changes relative to baseline were assessed. The key ECG endpoint was change from baseline in QT interval corrected with Fridericia's method (ΔQTcF)...
October 28, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27795519/diagnostics-for-multiple-myeloma
#13
Etsuko Yamazaki
Multiple myeloma (MM) has been diagnosed based on the International Myeloma Working Group (IMWG) diagnostic criteria since 2003. In 2014, the IMWG updated these diagnostic criteria to add three specific biomarkers, i.e., 1) Clonal bone marrow plasma cell percentage ≥60%; 2) Involved: uninvolved serum free light chain ratio ≥100; 3) >1 focal lesion on MRI studies, based on CRAB features (hypercalcemia, renal failure, anemia, and bone lesions). An early diagnosis of MM can be made, allowing timely anti-MM treatment, in patients with the ultra-high-risk smoldering form of this disease...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/27768092/prevalence-incidence-and-survival-of-smoldering-multiple-myeloma-in-the-united-states
#14
A Ravindran, A C Bartley, S J Holton, W I Gonsalves, P Kapoor, M A Siddiqui, S K Hashmi, A L Marshall, A A Ashrani, A Dispenzieri, R A Kyle, S V Rajkumar, R S Go
No abstract text is available yet for this article.
October 21, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27757215/brentuximab-vedotin-therapy-for-cutaneous-lesions-in-t-prolymphocytic-leukemia-a-case-report
#15
Jordan Senchak, Peter Pickens
We present an 88-year-old male with simultaneous T-cell prolymphocytic leukemia and stable smoldering myeloma with excellent initial response to three months of alemtuzumab. The patient relapsed at twelve months with severe cutaneous disease. Biopsy of a representative plaque demonstrated CD30 positivity in rare malignant lymphocytes. The patient demonstrated no response to reintroduction with a full course of alemtuzumab. He was therefore treated with brentuximab vedotin, resulting in partial remission of skin involvement that persisted for three months...
September 28, 2016: Hematology Reports
https://www.readbyqxmd.com/read/27737890/mgus-to-myeloma-a-mysterious-gammopathy-of-underexplored-significance
#16
REVIEW
Madhav V Dhodapkar
All cases of multiple myeloma (MM) are preceded by precursor states termed monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (SMM). Genetic analyses of MGUS cells have provided evidence that it is a genetically advanced lesion, wherein tumor cells carry many of the genetic changes found in MM cells. Intraclonal heterogeneity is also established early during the MGUS phase. Although the genetic features of MGUS or SMM cells at baseline may predict disease risk, transition to MM involves altered growth of preexisting clones...
December 8, 2016: Blood
https://www.readbyqxmd.com/read/27716740/high-levels-of-periostin-correlate-with-increased-fracture-rate-diffuse-mri-pattern-abnormal-bone-remodeling-and-advanced-disease-stage-in-patients-with-newly-diagnosed-symptomatic-multiple-myeloma
#17
E Terpos, D Christoulas, E Kastritis, T Bagratuni, M Gavriatopoulou, M Roussou, A Papatheodorou, E Eleutherakis-Papaiakovou, N Kanellias, C Liakou, I Panagiotidis, M Migkou, P Kokkoris, L A Moulopoulos, M A Dimopoulos
Periostin is an extracellular matrix protein that is implicated in the biology of normal bone remodeling and in different cancer cell growth and metastasis. However, there is no information on the role of periostin in multiple myeloma (MM). Thus, we evaluated periostin in six myeloma cell lines in vitro; in the bone marrow plasma and serum of 105 newly diagnosed symptomatic MM (NDMM) patients and in the serum of 23 monoclonal gammopathy of undetermined significance (MGUS), 33 smoldering MM (SMM) patients, 30 patients at the plateau phase post-first-line therapy, 30 patients at first relapse and 30 healthy controls...
October 7, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27698801/combined-use-of-free-light-chain-and-heavy-light-chain-ratios-allow-diagnosis-and-monitoring-of-patients-with-monoclonal-gammopathies-experience-of-a-single-institute-with-three-exemplar-case-reports
#18
Alfredo Gagliardi, Claudio Carbone, Angela Russo, Rosanna Cuccurullo, Anna Lucania, Paola Della Cioppa, Gabriella Misso, Michele Caraglia, Catello Tommasino, Lucia Mastrullo
Monoclonal gammopathies are characterized by serum monoclonal component (MC) plus an intact immunoglobulin and a free light chain (FLC), or a combination of both. The measurement of FLC with Freelite(®) is the standard practice recommended by International Myeloma Working Group guidelines. Recently, Hevylite(®) heavy/light chains (HLC) assays were introduced to specifically target junctional epitopes between the heavy and light chains of intact immunoglobulins, allowing the independent quantification of the involved (MC) and uninvolved (polyclonal immunoglobulin background) HLC isotype...
October 2016: Oncology Letters
https://www.readbyqxmd.com/read/27696254/mgus-and-smoldering-multiple-myeloma-diagnosis-and-epidemiology
#19
María-Victoria Mateos, Ola Landgren
Monoclonal gammopathy of undetermined significance (MHUS) is characterized by the presence of a serum M-protein less than 3 g/dL, less than 10 % clonal plasma cells in the bone marrow, and the absence of myeloma-defining event. Smoldering multiple myeloma (SMM) is an asymptomatic disorder characterized by the presence of ≥3 g/dL serum M-protein and/or 10-60 % bone marrow plasma cell infiltration with no myeloma-defining event. The risk of progression to multiple myeloma (MM) requiring therapy varies greatly for individual patients, but it is uniform and 1 % per year for MGUS, while higher (10 % per year) and not uniform for SMM patients...
2016: Cancer Treatment and Research
https://www.readbyqxmd.com/read/27622827/aberrant-p15-p16-p53-and-dapk-gene-methylation-in-myelomagenesis-clinical-and-prognostic-implications
#20
Catarina Geraldes, Ana Cristina Gonçalves, Emília Cortesão, Marta Isabel Pereira, Adriana Roque, Artur Paiva, Letícia Ribeiro, José Manuel Nascimento-Costa, Ana Bela Sarmento-Ribeiro
BACKGROUND: Aberrant DNA methylation is considered a crucial mechanism in the pathogenesis of monoclonal gammopathies. We aimed to investigate the contribution of hypermethylation of 4 tumor suppressor genes to the multistep process of myelomagenesis. METHODS: The methylation status of p15, p16, p53, and DAPK genes was evaluated in bone marrow samples from 94 patients at diagnosis: monoclonal gammopathy of uncertain significance (MGUS) (n = 48), smoldering multiple myeloma (SMM) (n = 8) and symptomatic multiple myeloma (MM) (n = 38), and from 8 healthy controls by methylation-specific polymerase chain reaction analysis...
December 2016: Clinical Lymphoma, Myeloma & Leukemia
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