IMWG Guidelines for Facilities and Services for the Management of Myeloma Patients

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The following guidelines are excerpted from Palumbo et al, International Myeloma Working Group Guidelines for the Management of Multiple Myeloma Patients Ineligible for Standard High-Dose Chemotherapy with Autologous Stem Cell Transplantation, Leukemia (2009), 1-15. The most important feature of any clinical unit established to care for myeloma patients is the training and expertise of the medical staff.   Below are the diagnostic and specialty services required to support treatment decision-making and patient management.  Patient support services, though desirable hallmarks of a good specialty center, are not absolutely essential. Facilities It is recommended that a special clinical unit be developed devoted to the treatment of MM, with clear policies and protocols for […]

Survival and years of life lost in different age cohorts of patients with multiple myeloma

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PURPOSE: To assess the impact of age on outcome and to analyze the projected years of life lost in patients with multiple myeloma. PATIENTS AND METHODS: Ten thousand five hundred forty-nine patients were evaluated; 6,996 patients were treated with conventional chemotherapy, and 3,553 patients were treated with high-dose therapy with autologous stem-cell transplantation. RESULTS: Mean observed and relative overall survival times in the entire cohort were 3.7 and 3.9 years, respectively. Observed survival decreased steadily from 6.4 years in patients younger than age 50 years to 2.5 years in patients > or = age 80 years. A similar decrease was noted for relative survival. Higher age correlated significantly with higher […]

IMWG Guidelines on Imaging Techniques in the Diagnosis and Monitoring of Multiple Myeloma

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Up to 90% of myeloma patients develop osteolytic lesions, a major cause of morbidity and mortality, during the course of their disease. 2  Appropriate use of imaging techniques is essential to identify and characterize skeletal complications resulting from MM, to determine the extent of intramedullary and extramedullary foci, and to evaluate disease progression. Several imaging techniques are used to clarify bone and soft tissue disease in the diagnosis and management of myeloma: conventional radiography, computed tomography (CT), magnetic resonance imaging (MRI), and nuclear medicine imaging. The following International Myeloma Working Group (IMWG) guidelines provide recommendations for the use of each of the technologies. The appropriate use of these various technologies […]

IMWG Guidelines for the Use of Bisphosphonates in Myeloma

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Intravenous bisphosphonate therapy has been amply demonstrated to reduce bone complications of myeloma.   Bisphosphonate (BP) therapy is therefore an important component of supportive care for myeloma patients with boney disease. Adverse events associated with BP are usually mild and consist of fever, renal function impairment, myalgias, and hypocalcemia.  A more serious potential side effect of bisphosphonate therapy that was first identified in 20031 is osteonecrosis of the jaw (ONJ), a debilitating problem that can be associated with significant morbidity. The following guidelines for the use of bisphosphonate therapy in myeloma are based upon IMWG and Mayo Clinic guidelines2,3 and are intended to provide safe criteria for bisphosphonate use to minimize […]

Genetic polymorphisms of EPHX1, Gsk3beta, TNFSF8 and myeloma cell DKK-1 expression linked to bone disease in myeloma

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Bone disease in myeloma occurs as a result of complex interactions between myeloma cells and the bone marrow microenvironment. A custom-built DNA single nucleotide polymorphism (SNP) chip containing 3404 SNPs was used to test genomic DNA from myeloma patients classified by the extent of bone disease. Correlations identified with a Total Therapy 2 (TT2) (Arkansas) data set were validated with Eastern Cooperative Oncology Group (ECOG) and Southwest Oncology Group (SWOG) data sets. Univariate correlates with bone disease included: EPHX1, IGF1R, IL-4 and Gsk3beta. SNP signatures were linked to the number of bone lesions, log(2) DKK-1 myeloma cell expression levels and patient survival. Using stepwise multivariate regression analysis, the following SNPs: […]

International myeloma working group (IMWG) consensus statement and guidelines regarding the current status of stem cell collection and high-dose therapy for multiple myeloma and the role of plerixafor (AMD 3100)

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Multiple myeloma is the most common indication for high-dose chemotherapy with autologous stem cell support (ASCT) in North America today. Stem cell procurement for ASCT has most commonly been performed with stem cell mobilization using colony-stimulating factors with or without prior chemotherapy. The target CD34+ cell dose to be collected as well as the number of apheresis performed varies throughout the country, but a minimum of 2 million CD34+ cells/kg has been traditionally used for the support of one cycle of high-dose therapy. With the advent of plerixafor (AMD3100) (a novel stem cell mobilization agent), it is pertinent to review the current status of stem cell mobilization for myeloma as […]

International Myeloma Working Group molecular classification of multiple myeloma: spotlight review

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Myeloma is a malignant proliferation of monoclonal plasma cells. Although morphologically similar, several subtypes of the disease have been identified at the genetic and molecular level. These genetic subtypes are associated with unique clinico- pathological features and dissimilar outcome. At the top hierarchical level, myeloma can be divided into hyperdiploid and non-hyperdiploid subtypes. The latter is mainly composed of cases harboring IgH translocations, generally associated with more aggressive clinical features and shorter survival. The three main IgH translocations in myeloma are the t(11;14)(q13;q32), t(4;14)(p16;q32) and t(14;16)(q32;q23). Trisomies and a more indolent form of the disease characterize hyperdiploid myeloma. A number of genetic progression factors have been identified including deletions of […]

Mobilization in myeloma revisited: IMWG consensus perspectives on stem cell collection following initial therapy with thalidomide-, lenalidomide-, or bortezomib-containing regimens

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The past decade has witnessed a paradigm shift in the initial treatment of multiple myeloma with the introduction of novel agents such as thalidomide, lenalidomide, and bortezomib, leading to improved outcomes. High-dose therapy and autologous stem cell transplantation remains an important therapeutic option for patients with multiple myeloma eligible for the procedure. Before the advent of the novel agents, patients underwent stem cell collection prior to significant alkylating agent exposure, given its potential deleterious effect on stem cell collection. With increasing use of the novel agents in the upfront setting, several reports have emerged raising concerns about their impact on the ability to collect stem cells. An expert panel of […]

International myeloma working group consensus statement and guidelines regarding the current role of imaging techniques in the diagnosis and monitoring of multiple Myeloma

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Several imaging technologies are used for the diagnosis and management of patients with multiple myeloma (MM). Conventional radiography, computed tomography (CT), magnetic resonance imaging (MRI) and nuclear medicine imaging are all used in an attempt to better clarify the extent of bone disease and soft tissue disease in MM. This review summarizes all available data in the literature and provides recommendations for the use of each of the technologies. Conventional radiography still remains the ‘gold standard’ of the staging procedure of newly diagnosed and relapsedmyeloma patients. MRI gives information complementary to skeletal survey and is recommended in MM patients with normal conventional radiography and in all patients with an apparently […]

Genetic associations with thalidomide mediated venous thrombotic events in myeloma identified using targeted genotyping

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A venous thromboembolism (VTE) with the subsequent risk of pulmonary embolism is a major concern in the treatment of patients with multiple myeloma with thalidomide. The susceptibility to developing a VTE in response to thalidomide therapy is likely to be influenced by both genetic and environmental factors. To test genetic variation associated with treatment related VTE in patient peripheral blood DNA, we used a custom-built molecular inversion probe (MIP)-based single nucleotide polymorphism (SNP) chip containing 3404 SNPs. SNPs on the chip were selected in “functional regions” within 964 genes spanning 67 molecular pathways thought to be involved in the pathogenesis, treatment response, and side effects associated with myeloma therapy. Patients […]