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Smoldering myeloma

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https://www.readbyqxmd.com/read/28417905/analytical-criticalities-associated-to-different-immunological-methods-for-serum-free-light-chain-detection-in-plasma-cell-dyscrasias-a-description-of-particular-clinical-cases
#1
Rocco Sabatino, Antonio Perrone, Marco Cuomo, Sandra Liotti, Vittoria Barchiesi, Monica Cantile, Ernesta Cavalcanti
Current criteria for differential diagnosis of multiple myeloma (MM), Monoclonal gammopathy of undetermined significance (MGUS), and smoldering multiple myeloma (SMM) are included in the 2003 guidelines by the International Myeloma Working Group (IMWG). An updated version was then published in 2014, highlighting the importance of serum free light chain (sFLC) detection, as well as the κ/λ ratio as excellent indicators of clonality. At present, two commercial assays for sFLC quantification are available: the Freelite™ assay and the N-Latex assay...
April 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28341370/management-of-smoldering-myeloma-on-behalf-of-spanish-myeloma-group
#2
María-Victoria Mateos, Joan Bladé, Juan-José Lahuerta, Jesús San-Miguel
No abstract text is available yet for this article.
March 21, 2017: Medicina Clínica
https://www.readbyqxmd.com/read/28316846/donor-derived-smoldering-multiple-myeloma-following-a-hematopoietic-cell-transplantation-for-aml
#3
Bita Fakhri, Mark Fiala, Michael Slade, Peter Westervelt, Armin Ghobadi
Posttransplant Lymphoproliferative Disorder (PTLD) is one of the most common malignancies complicating solid organ transplantation. In contrast, PTLD accounts for a minority of secondary cancers following allogeneic hematopoietic cell transplantation (HCT). Here we report on a 61-year-old woman who received an ABO-mismatched, HLA-matched unrelated donor hematopoietic cell transplantation from a presumably healthy donor for a diagnosis of acute myeloid leukemia (AML). Eighteen months following her transplant, she developed a monoclonal gammopathy...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28286629/impact-of-crab-symptoms-in-survival-of-patients-with-symptomatic-myeloma-in-novel-agent-era
#4
Aya Nakaya, Shinya Fujita, Atsushi Satake, Takahisa Nakanishi, Yoshiko Azuma, Yukie Tsubokura, Masaaki Hotta, Hideaki Yoshimura, Kazuyoshi Ishii, Tomoki Ito, Shosaku Nomura
The acronym CRAB summarizes the most typical clinical manifestations of multiple myeloma, these being hypercalcemia, renal failure, anemia, and bone disease. CRAB can be used to distinguish between active, symptomatic multiple myeloma and monoclonal gammopathy of undermined significance or smoldering myeloma. The distinction is relevant not only for classification and diagnosis but also for therapy. CRAB factors influence the prognosis of multiple myeloma. However, it is unclear whether the presence of CRAB factors has an influence on the prognosis of myeloma treated with novel agents...
February 23, 2017: Hematology Reports
https://www.readbyqxmd.com/read/28229908/multiple-myeloma-tumor-cells-are-selectively-killed-by-pharmacologically-dosed-ascorbic-acid
#5
Jiliang Xia, Hongwei Xu, Xiaoyan Zhang, Chantal Allamargot, Kristen L Coleman, Randy Nessler, Ivana Frech, Guido Tricot, Fenghuang Zhan
High-dose chemotherapies to treat multiple myeloma (MM) can be life-threatening due to toxicities to normal cells and there is a need to target only tumor cells and/or lower standard drug dosage without losing efficacy. We show that pharmacologically-dosed ascorbic acid (PAA), in the presence of iron, leads to the formation of highly reactive oxygen species (ROS) resulting in cell death. PAA selectively kills CD138(+) MM tumor cells derived from MM and smoldering MM (SMM) but not from monoclonal gammopathy undetermined significance (MGUS) patients...
February 16, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28201978/multiple-myeloma-and-the-immune-microenvironment
#6
Yawara Kawano, Aldo M Roccaro, Jamil Azzi, Irene M Ghobrial
One of the great advances in the field of cancer therapy in recent years is the emergence of immune therapies. Immune therapies, especially immune checkpoint inhibitors, have shown promising results in pre-clinical models and clinical trials of solid tumors, such as melanoma, breast cancer and lung cancer. Therapeutic strategies targeting the immune microenvironment have also been applied to hematological malignancies such as multiple myeloma (MM), a plasma cell neoplasia characterized by clonal expansion of malignant plasma cells mainly in the bone marrow (BM)...
February 13, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28188192/multiple-myeloma-version-3-2017-nccn-clinical-practice-guidelines-in-oncology
#7
Shaji K Kumar, Natalie S Callander, Melissa Alsina, Djordje Atanackovic, J Sybil Biermann, Jason C Chandler, Caitlin Costello, Matthew Faiman, Henry C Fung, Cristina Gasparetto, Kelly Godby, Craig Hofmeister, Leona Holmberg, Sarah Holstein, Carol Ann Huff, Adetola Kassim, Michaela Liedtke, Thomas Martin, James Omel, Noopur Raje, Frederic J Reu, Seema Singhal, George Somlo, Keith Stockerl-Goldstein, Steven P Treon, Donna Weber, Joachim Yahalom, Dorothy A Shead, Rashmi Kumar
Multiple myeloma (MM) is caused by the neoplastic proliferation of plasma cells. These neoplastic plasma cells proliferate and produce monoclonal immunoglobulin in the bone marrow causing skeletal damage, a hallmark of multiple myeloma. Other MM-related complications include hypercalcemia, renal insufficiency, anemia, and infections. The NCCN Multiple Myeloma Panel members have developed guidelines for the management of patients with various plasma cell dyscrasias, including solitary plasmacytoma, smoldering myeloma, multiple myeloma, systemic light chain amyloidosis, and Waldenström's macroglobulinemia...
February 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28158311/a-single-arm-open-label-phase-2-clinical-trial-evaluating-disease-response-following-treatment-with-bi-505-a-human-anti-intercellular-adhesion-molecule-1-monoclonal-antibody-in-patients-with-smoldering-multiple-myeloma
#8
Stina Wichert, Gunnar Juliusson, Åsa Johansson, Elisabeth Sonesson, Ingrid Teige, Anna Teige Wickenberg, Björn Frendeus, Magnus Korsgren, Markus Hansson
BACKGROUND: Smoldering multiple myeloma (SMM) is an indolent disease stage, considered to represent the transition phase from the premalignant MGUS (Monoclonal Gammopathy of Undetermined Significance) state towards symptomatic multiple myeloma (MM). Even though this diagnosis provides an opportunity for early intervention, few treatment studies have been done and the current standard of care is observation until progression. BI-505, a monoclonal antibody directed against intercellular adhesion molecule 1 (ICAM-1) with promising anti-myeloma activity in preclinical trials, is a possible treatment approach for this patient category with potential to eliminate tumor cells with minimal long-term side effects...
2017: PloS One
https://www.readbyqxmd.com/read/28140696/siltuximab-and-hematologic-malignancies-a-focus-in-non-hodgkin-lymphoma
#9
REVIEW
Andrea Ferrario, Michele Merli, Claudia Basilico, Margherita Maffioli, Francesco Passamonti
The role of interleukin-6 (IL-6) in tumorigenesis and in particular in haematological malignancies is crucial. On the basis of the favourable results obtained in the subset of multicentric Castleman disease (MCD), Siltuximab, a chimeric, human-murine, immunoglobulin (Ig) Gk monoclonal antibody directed against human IL-6 has been evaluated in haematological malignancies such as multiple myeloma, myelodisplastic syndromes and non Hodgkin lymphomas. Areas covered: This review discusses available data related to the role of IL-6 as a therapeutic target, the characteristics of Siltuximab in term pharmacokinetics and pharmacodynamics properties and a detailed analysis of the studies involving haematological malignancies with a peculiar focus on non Hodgkin lymphoma...
March 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28061989/high-risk-smoldering-myeloma-perspective-on-watchful-monitoring
#10
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
#11
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
#12
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
#13
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
#14
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...
March 2017: Kidney International
https://www.readbyqxmd.com/read/27983725/a-gene-expression-inflammatory-signature-specifically-predicts-multiple-myeloma-evolution-and-patients-survival
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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