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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many studies have characterized the role of growth factors in multiple myeloma (MM) pathogenesis and have derived novel therapies to improve patient outcome based upon targeting cytokines and their signaling cascades both in the MM cell and in the bone-marrow (BM) microenvironment. These cytokines include interleukin 6 (IL-6), insulin-like growth factor 1 (IGF-1), vascular endothelial growth factor (VEGF), tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta), stromal cell-derived factor 1alpha (SDF-1alpha), IL-21, B-cell stimulating factor 3 (BSF-3) and fibroblast growth factor (FGF). These cytokines are secreted from stromal cells (SCs), endothelial cells and/or osteoclasts, and promote MM cell growth, survival and migration, as well as paracrine cytokine secretion and angiogenesis in the BM milieu. Thus inhibition of signaling cascades induced by these cytokine provides rationale for a therapeutic option for MM.
Best Pract Res Clin Haematol 2005
PMID:Cytokines and signal transduction. 1602 34

In recent years, we have seen an explosion in knowledge of the genetics and cytogenetics of the plasma-cell neoplasms. This chapter will deal with these advances and will place them in the integrative context of the pathophysiologic basis of the disease, and will discuss the important clinical implications of these abnormalities. We have learned that myeloma can be classified into increasingly definable subgroups that follow a basic global hierarchical grouping. All gene expression profiling strategies have come to similar conclusions and confirm the subgroups previously identified by karyotype, molecular cytogenetics and other genetic studies. At the top level there are two major pathogenetic pathways for the development of plasma cell tumors: one that is associated with hyperdiploidy and one that is characterized by the presence of chromosome translocations involving the immunoglobulin heavy chain locus (IgH). These translocations are seen in up to 60% of patients, but involve a common recurrent chromosome partner in only 40-50% of patients. Several genetic markers are now shown to be associated with a shortened survival. Of these, the most common ones include abnormalities (deletion and monosomy) of chromosome 13, the global state of hypodiploidy and abnormalities of chromosome 1. Many of the translocations observed in MM are also seen in monoclonal gammopathy of undetermined significance (MGUS), even in individuals without progression to full malignant disease for many years. The identification of critical genetic lesions will pave the way for the development of disease-targeted therapy.
Best Pract Res Clin Haematol 2005
PMID:Genetics of multiple myeloma. 1602 35

Gene expression profiling is a powerful tool through which the biology of multiple myeloma can be dissected. We will describe in this chapter how early studies using this technology have provided meaningful insights into myeloma biology, have led to the identification of new therapeutic targets, and have identified powerful prognostic and pharmacogenomic markers. Specifically, we will demonstrate that gene expression profiling can be used to segregate myeloma patients into prognostic categories within which known IgH translocation signatures can be readily defined. We also show that expression signatures can identify patients with chromosome 13 deletion. Finally, we demonstrate that global gene expression signatures can be distilled to short lists of three genes or more which together impart clinical outcome information, which is significantly more powerful than any previously defined prognostic tool. Expression profiling has also led to the identification of a number of new therapeutic targets not only in myeloma cell survival but also in the pathogenesis of the osteolysis which is a hallmark of this disease.
Best Pract Res Clin Haematol 2005
PMID:Gene expression profiling and multiple myeloma. 1602 36

Multiple myeloma is a malignant plasma-cell proliferative disease with an expected 15,270 new cases and 11,070 deaths in the USA in 2004 alone. This accounts for 1% of all malignancies and slightly more than 10% of all hematologic malignancies in Caucasians and 20% in African Americans. The diagnosis is based on the presence of bone pain, anemia, and plasma-cell infiltrate in the bone marrow or within bone lesions. It is essential that the spectrum of plasma-cell proliferative disorders be recognized: monoclonal gammopathy of undetermined significance (MGUS), smoldering (asymptomatic) multiple myeloma (SMM), and active (symptomatic) MM. These distinctions affect important management decisions. Other related disorders include primary systemic amyloidosis, POEMS syndrome, and acquired Fanconi syndrome.
Best Pract Res Clin Haematol 2005
PMID:Multiple myeloma: clinical features and indications for therapy. 1602 37

The outcome of myeloma patients is highly heterogeneous, with survival ranging from a few months to more than 10 years. Accordingly, investigation of prognostic factors may contribute to identification of risk categories and to provision of more accurate information about individual disease outcome. For many years prognostic factors have relied on clinical parameters such as age, hemoglobin level and renal function. Subsequently, biological parameters such as the proliferative activity of plasma cells and beta2-microglobulin have been added to the prognostic arsenal. More recently, cytogenetic and molecular markers with significant influence on disease outcome have been identified. Here we will review the most relevant prognostic factors reported in the literature in patients treated with both conventional chemotherapy and high-dose therapy followed by autologous stem-cell support, as well as in asymptomatic MM and MGUS patients.
Best Pract Res Clin Haematol 2005
PMID:Prognostic features of multiple myeloma. 1602 38

The treatment of multiple myeloma (MM) has undergone major changes in the last decade. There is now an array of therapeutic options, including autologous stem-cell transplantation, non-myeloablative (mini) allogeneic transplantation, and new drugs such as thalidomide and bortezomib. There is also an awareness that there are subsets of patients with MM who have not gained much from the recent advances, including patients with certain adverse prognostic factors (high-risk MM). In this article, we outline our approach to the diagnosis, risk stratification and treatment of MM with a focus on conventional therapy. We incorporate a risk-based strategy for the treatment of MM that also takes into account the eligibility of the patient to undergo stem-cell transplantation. We also outline the role and current indications for the use of new active agents in this disease.
Best Pract Res Clin Haematol 2005
PMID:Conventional therapy and approach to management. 1602 39

In patient with newly diagnosed multiple myeloma (MM), randomized studies have shown that autologous stem-cell transplantation (ASCT) is superior to conventional chemotherapy, and ASCT is now standard care, at least for younger patients. The best conditioning regimen is melphalan 200 mg/m2, and the best stem-cell source is unselected peripheral progenitor cells. Recent results of the IFM94 trial show that double ASCT is superior to single ASCT, at least in patients who do not achieve a 90% response after one transplant. By combining biologic markers (beta2-microglobulin, albumin) and genetic markers (hypodiploidy, chromosome 13 deletion) it is possible to accurately predict prognosis after ASCT. The results of allogeneic SCT remain disappointing due to a high transplant mortality. Strategies combining ASCT and reduced-intensity allogeneic SCT are currently being studied.
Best Pract Res Clin Haematol 2005
PMID:Stem-cell transplantation in multiple myeloma. 1602 40

The therapeutic management of multiple myeloma (MM) for the last several decades has mainly involved regimens based on use of glucocorticoids and cytotoxic chemotherapeutics. Despite progress in delineating the activity of such regimens, at either conventional or high doses, MM has remained an incurable disease, without substantial improvement in the median overall survival. This has sparked major interest in the development of novel therapies that in part capitalize on recent advances in our understanding of the biology of MM, including the molecular mechanisms by which MM cell-host bone marrow (BM) interactions regulate tumor-cell growth, survival, and drug resistance in the BM milieu. The development of in vitro and in vivo models of MM-stromal interactions has allowed not only for better characterization of these molecular phenomena but also for identification of specific therapeutic strategies to overcome these interactions and achieve an enhanced anti-MM effect, even against MM resistant to conventional therapies. Herein, we review the latest progress in the development of these novel anti-MM therapies, with major focus on therapies which have translated from preclinical evaluation to clinical application, including thalidomide and its more potent immunomodulatory (IMiD) derivatives, the first-in-class proteasome inhibitor bortezomib (formerly known as PS-341), and arsenic trioxide (As2O3).
Best Pract Res Clin Haematol 2005
PMID:Novel biological therapies for the treatment of multiple myeloma. 1602 41

Renal failure is a common complication in patients with multiple myeloma. It is generally due to tubular light-chain damage, and it is reversible in about 50% of patients. The reversibility rate depends on the degree of light-chain nephropathy. The initial therapy should consist of dexamethasone- or cyclophosphamide-based regimens. High-dose therapy/autologous transplant may be of benefit in selected patients. Early plasma exchange may be useful in patients who have severe renal failure but do not yet require dialysis. Renal replacement with dialysis is a worthwhile measure in patients with end-stage renal failure. Anemia is the most common hematologic complication. About 70% of anemic patients respond to recombinant human erythropoietin (rHuEPO), resulting not only in an increase in the hemoglobin level but also in an improvement in the quality of life. The hemoglobin level should ideally be maintained at around 12 g/dL. Infection is the main cause of morbidity and mortality in patients with myeloma. The highest risk of infection is within the first 2 months of initiation of therapy as well as in patients with renal failure and in those with relapsed and refractory disease.
Best Pract Res Clin Haematol 2005
PMID:Renal, hematologic and infectious complications in multiple myeloma. 1602 42

The major clinical manifestation of multiple myeloma is related to the osteolytic bone destruction. The bone disease can lead to pathologic fractures, spinal cord compression, hypercalcemia, and pain. It is also a major cause of morbidity and mortality in these patients. These patients frequently require radiation therapy, surgery and analgesic medications. Bisphosphonates are specific inhibitors of osteoclastic activity, and these agents have been evaluated in myeloma patients with bone disease during the past 15 years. Several large randomized trials have been conducted in myeloma patients also receiving chemotherapy. Orally administered bisphosphonates have shown little ability to slow the development of skeletal complications in these patients. In contrast, more potent intravenous monthly infusions of either pamidronate or zoledronic acid have reduced the skeletal complications among these patients and are now a mainstay of myeloma therapy. A number of other types of new anti-bone-resorptive agents are also in early clinical development.
Best Pract Res Clin Haematol 2005
PMID:Myeloma bone disease. 1602 43


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