Management of monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM).
ABSTRACT Monoclonal gammopathy of undetermined significance (MGUS) is defined as a serum M protein level of less than 3 g/dL, less than 10% clonal plasma cells in the bone marrow, and the absence of end-organ damage. The prevalence of MGUS is 3.2% in the white population but is approximately twice that high in the black population. MGUS may progress to multiple myeloma, AL amyloidosis, Waldenström macroglobulinemia, or lymphoma. The risk of progression is approximately 1% per year, but the risk continues even after more than 25 years of observation. Risk factors for progression include the size of the serum M protein, the type of serum M protein, the number of plasma cells in the bone marrow, and the serum free light chain ratio. Smoldering (asymptomatic) multiple myeloma (SMM) is characterized by the presence of an M protein level of 3 g/dL or higher and/or 10% or more monoclonal plasma cells in the bone marrow but no evidence of end-organ damage. The overall risk of progression to a malignant condition is 10% per year for the first 5 years, approximately 3% per year for the next 5 years, and 1% to 2% per year for the following 10 years. Patients with both MGUS and SMM must be followed up for their lifetime.
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ABSTRACT: This article continues a series on literature-based followup recommendations for conditions commonly encountered in general oncology practice. The accidental discovery of a monoclonal gammopathy (monoclonal protein or M protein, M spike) becomes increasingly common with advanced patient age, affecting approximately 3% to 4% of those over age 50, 5% over age 65 and almost 10% of those 85 or older. Since adult oncology practice is largely concerned with individuals 60 years and older, all oncologists require some familiarity with the investigation, natural history, followup and timing of subspecialist referral of patients with monoclonal gammopathy of undetermined significance (MGUS). Earlier studies suggest that in over 50% of patients in whom an M protein was accidentally detected, no subsequent followup was actually undertaken.5 In order to facilitate an orderly approach, this article utilizes a question-based format to address the most common concerns that arise when oncologists are confronted with a monoclonal protein. Virtually no randomized data exist on this topic, so references are primarily literature-based consensus guidelines and recommendations. Key words MGUS, monoclonal gammopathy, M spike, M protein, Waldenström macroglobulinemia, multiple myeloma, smouldering multiple myeloma, systemic amyloidosis
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ABSTRACT: Targeted modulation of microenvironmental regulatory pathways may be essential to control myeloma and other genetically/clonally heterogeneous cancers. Here we report that human myeloma-associated monocytes/macrophages (MAM), but not myeloma plasma cells, constitute the predominant source of interleukins (IL)1β, IL10 and TNFα at diagnosis, whereas IL6 originates from stromal cells and macrophages. To dissect MAM activation/cytokine pathways, we analyzed Toll-like receptor (TLR) expression in human myeloma CD14+ cells. We observed co-regulation of TLR2 and TLR6 expression correlating with local processing of versican, a proteoglycan TLR2/6 agonist linked to carcinoma progression. Versican has not been mechanistically implicated in myeloma pathogenesis. We hypothesized that the most readily accessible target in the versican-TLR2/6 pathway would be the MAP3-kinase, TPL2 (Cot/MAP3K8). Ablation of Tpl2 in the genetically-engineered in vivo myeloma model, Vκ*MYC, led to prolonged disease latency associated with plasma cell growth defect. Tpl2 loss abrogated the "inflammatory switch" in macrophages within nascent myeloma lesions and licensed macrophage repolarization in established tumors. MYC activation/expression in plasma cells was independent of Tpl2 activity. Pharmacologic TPL2 inhibition in human monocytes led to dose-dependent attenuation of IL1β induction/secretion in response to TLR2 stimulation. Our results highlight a TLR2/6-dependent TPL2 pathway as novel therapeutic target acting non-autonomously through macrophages to control myeloma progression.Blood 04/2014; 123(21). DOI:10.1182/blood-2014-02-554071 · 9.78 Impact Factor
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ABSTRACT: Oncology nurses working in ambulatory care often encounter patients with nonmalignant hematologic disorders because the specialties of hematology and oncology are closely entwined. A variety of nonmalignant hematologic disorders can evolve into blood malignancies; therefore, close surveillance of nonmalignant hematologic disorders in an oncology/hematology clinic is important for early detection of malignancy. Monoclonal gammopathy of undetermined significance (MGUS) is one nonmalignant, hematologic disorder that is usually aproblematic; however, it can evolve into a blood malignancy such as multiple myeloma or be associated with other chronic conditions. This article provides an overview of MGUS with a focus on implications for the oncology nurse and patient education.Clinical Journal of Oncology Nursing 12/2013; 17(6):614-9. DOI:10.1188/13.CJON.614-619