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Results for “MULTIPLE MYELOMA”

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PubMed1998

[Prognostic factors and standard therapy of multiple myeloma].

Multiple myeloma (MM) is a B-cell non-Hodgkins lymphoma with a neoplastic proliferation of plasma cells in the bone marrow. In different studies median survival time has been measured between 19 and 50 months. Several prognostic factors help to subdivide the patient population in risk groups. The treatment is palliative until now and the individual concept of therapy includes chemotherapy, radiotherapy and other treatment modalities. Evidence of progressive or symptomatic disease is usually required for initiation of chemotherapy.

Diphosphonates↗

PubMedDate not supplied

[Hematopoietic stem cell transplantation in multiple myeloma].

Multiple myeloma (MM) is the second most common hematologic malignancy, affecting approximately 14,000 new patients per year in the United States. For over four decades, the standard treatment for MM has been a regimen of melphalan combined with prednisone. Using this treatment modality, complete responses are rare, and 50% of patients have had disease that was resistant to chemotherapy. Attempts have been made to improve the outcome of MM by administering combinations of i.v. poli-chemotherapy, but these treatments are equivalent in terms of overall survival. High-dose therapy with peripheral blood stem cell support can be applied safely in these patients and achieves significantly higher complete remission rates as well as better event-free survival and overall survival. However, neither tumor-cell purging, positive selection, intensification of conditioning with additional chemotherapeutic agents, nor total body irradiation have been shown to improve outcome. The role of tandem transplantation with high-dose melphalan seems to be a good selection of treatment in hospitals having all resources. Future research will include the combination of the best remission-induction regimen with tandem transplants and maintenance treatments (thalidomide, idiotype or dendritic cell vaccination) that will sustain complete remission. Development of non-myeloablative allogeneic transplantation in order to exploit the graft-versus myeloma effect provides an alternative for patients who have a compatible donor. Combining all of these modalities with the new drugs developed few years ago (thalidomide, bortezomib, revlimid), we hope that MM will become a manageable chronic disease and perhaps a curable disease at least for 30% to 40% of the patients.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

Angiogenesis in multiple myeloma.

Multiple myeloma (MM) was the first haematological malignancy in which a prognostic relevance of bone marrow microvessel density (MVD) was shown. Myeloma-induced angiogenesis involves either the direct production of angiogenic molecules by myeloma cells or their induction in bone marrow stromal cells or endothelial cells (EC). Recent data demonstrate an increased angiogenic potential and a paracrine stimulatory effect of bone marrow EC on plasma cells (PC) in MM. Soluble angiogenic factors are elevated in bone marrow (BM) and in peripheral blood samples from myeloma patients. Furthermore, correlation with disease stage and prognosis was shown for serum levels of the angiogenic factors basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF). In this review we summarize recent data which give strong evidence for an increased angiogenic activity in bone marrow microenvironment and support the hypothesis that angiogenesis is not only an epiphenomenon of tumour growth but may also promote PC growth in MM.

Angiogenic Proteins↗

PubMed2003

[Isotype switching of produced immunoglobulins in multiple myeloma].

Multiple myeloma is usually characterized by production of a single serum monoclonal protein of constant isotype and light chain restriction. Isotype switching in human lymphomas appears to be an uncommon event. It could be due to altered para-protein production by the malignant plasma cell clone, or oligoclonal Ig production during recovery of B-cell function after chemotherapy. We describe a case of clonal heavy chain isotype switching in a patient with lymphoplasmocytic lymphoma.

Aged↗

PubMed2003

Novel therapeutic approaches for multiple myeloma.

Multiple myeloma (MM) affects 15,000 new patients annually in the US, with 50,000 total patients, and remains incurable. Our preliminary in vitro and animal studies suggest a role for MM-host interactions in regulating MM cell growth, drug resistance, and migration in the bone marrow. Importantly, treatment strategies which target mechanisms whereby MM cells grow and survive in the bone marrow, including thalidomide and its potent immunomodulatory derivatives and proteasome inhibitor PS-341, can overcome classical drug resistance in preclinical and early clinical studies.

Animals↗

PubMed2006

Investigational treatments for multiple myeloma.

Multiple myeloma remains a fatal neoplasm and new treatments are urgently needed. In recent years, advances in understanding the molecular pathophysiology of myeloma and the mechanisms of drug resistance led to the development of several novel agents. The drugs with the most available clinical data are thalidomide, bortezomib and lenalidomide. Impressive results obtained with these agents - both in relapsed disease and in newly diagnosed patients - have significantly improved the outcome of myeloma patients. Several other new targeted agents are presently under investigation. These include monoclonal antibodies, agents that target mammalian target of rapamycin, histone acetylation, heat-shock proteins, growth factor signalling cascades, oncogenes, signal transducer and activators of the transcription pathway, Akt pathway and MAPK pathway. Their mechanisms of action, the available knowledge on their efficacy, safety and possible future clinical application are reviewed.

Aged↗

PubMed2003

Recent developments in hematopoietic stem cell transplantation for multiple myeloma.

Multiple myeloma (MM) is often successfully controlled with conventional chemotherapy; however, complete remissions are uncommon, and cure is rare. High-dose therapy followed by administration of autologous or allogeneic stem cells, used for the treatment of MM in the past 15 years, is promising as a means of increasing remission rates and improving survival. Autologous transplantation has not always demonstrated survival benefits in randomized studies because most of the patients receiving transplants have relapses, whereas patients given conventional therapy can receive salvage transplants when relapse occurs. Efforts to improve the results of autologous transplantation include targeted radiation, tandem transplantation, and posttransplantation immunotherapy. Only allogeneic hematopoietic stem cell transplantation is potentially curative, owing to a graft-versus-myeloma effect. Although patients who receive either allogeneic or autologous stem cell transplants for MM have similar 3- to 5-year survival rates, only allograft recipients appear to enjoy long-term disease-free survival. High transplantation-related mortality associated with allogeneic stem cell transplantation is currently the major limitation to wider use of this potentially curative modality. Strategies designed to improve the therapeutic index of allografts include the use of nonablative conditioning regimens, peripheral blood cells rather than bone marrow, graft engineering, and targeted conditioning therapies, such as bone-seeking radioisotopes.

Hematopoietic Stem Cell Transplantation↗

PubMed2006

High-dose chemotherapy with autologous hematopoietic stem cell transplantation in patients with multiple myeloma.

Multiple myeloma, for all practical purposes, remains an incurable malignancy; however, 5-year survival has improved substantially during the past 30 years. A major contribution to improved outcome is the use of high-dose chemotherapy and stem cell transplantation. This multifaceted approach to therapy requires an understanding of appropriate induction therapy, techniques for stem cell mobilization, appropriate conditioning and supportive care. Also of importance are prognosis, features that predict outcome, the suitability of transplant candidates, and post-transplantation maintenance therapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2000

The role of interleukin-6 and interleukin-6/interleukin-6 receptor-alpha complex in the pathogenesis of multiple myeloma.

Multiple myeloma (MM) is a plasma-cell disorder in which malignant plasma cells accumulate in the bone marrow and usually produce a monoclonal immunoglobulin. Usual presenting features of overt MM include recurrent osteolytic lesions, bacterial infections, anemia and renal insufficiency. MM is responsible for about 1 percent of all cancer-related deaths in Western countries. Its epidemiologic pattern remains obscure, and its cause unknown [1]. The presence of somatic mutations within the immunoglobulin genes of myeloma cells indicate that the putative myeloma-cell precursors have been stimulated by antigens within germinal centers and are either memory B cells or migrating plasmablasts. Myeloma cells proliferate slowly in the bone marrow and display a weak apoptotic index in vivo [2]. This suggest that some defects in the apoptotic process could be involved in this neoplasia. Interleukin-6 (IL-6) is known to be an essential survival factor of myeloma cells and to protect them from apoptosis induced by different stimuli (e.g. dexamethasone, CD95, serum starvation, gamma-irradiation). More recently, important works have been devoted to the biology of the soluble form of the IL-6R alpha i.e., sIL-6R alpha. These works give IL-6/sIL-6R alpha complex an important role in the biology of IL-6. The purpose of the current review is to emphasize the role of this complex in the pathogenesis of MM.

Animals↗

PubMed2002

CD19 expression and growth inhibition of tumours in human multiple myeloma.

Multiple myeloma (MM) is a proliferative disorder of monoclonal plasma cells which accumulate in human bone marrow (BM). CD19 is a hallmark differentiation antigen of the B cell lineage and positively regulates antigen receptor signal transduction in mature B cells. We have previously shown that malignant plasma cells (myeloma cells) isolated from the MM patients lack the CD19 expression, while non-malignant plasma cells isolated from the healthy donors do express the CD19 antigens. It is also intriguing that there exists both CD19- and CD19+ plasma cells in some cases in pre-myeloma states including monoclonal gammopathy of undetermined significance (MGUS). It indicates that MGUS is usually composed of phenotypically non-malignant (CD19+) and malignant (CD19-) plasma cells. Furthermore, we recently demonstrate that, expression of the CD19 gene markedly inhibits the proliferation of human myeloma cell lines in vitro, and exhibits the reduced tumorigenicity in vivo and no anchorage-independent growth in vitro of a tumorigenic myeloma cell line. This inhibitory effect might result from the CD19-mediated intracellular signals because it is not observed in cells expressing the mutant CD19, which lacks the cytoplasmic domain. In this review, we suggest that loss of CD19 in MM could contribute to the proliferative advantage of the malignant plasma cell clones in this disease. Furthermore, we propose the usefulness of the phenotypic analysis of plasma cells in human plasma cell dyscrasia as a new diagnostic tool, and the CD19 gene as a potential target for the gene therapy in MM.

Antigens, CD19↗

PubMed2000

The role of human and viral cytokines in the pathogenesis of multiple myeloma.

Multiple myeloma (MM) is characterized by the accumulation of monoclonal plasma cells, a terminally differentiated form of B lymphocyte, in the bone marrow. This disease is most often associated with bone destruction, anemia and renal failure. Besides the malignant plasma cells, it has become clear that nonmalignant cells in the bone marrow also contribute to the development of this malignancy by the release of cytokines. Further support for the importance of the supporting cells comes from our recent finding of the human herpesvirus 8 (HHV-8) in the nonmalignant bone marrow stromal cells from these patients.

Cytokines↗

PubMed2003

[Pulmonary and chest wall involvement in multiple myeloma].

Multiple myeloma (MM) may manifest as diffuse bony disease (myelmatosis), as a solitary plasmacytoma of bone, or as extramedullary (extraosseous) plasmacytoma (EMP). The most frequent thoracic involvement by MM is bone involvement or pulmonary infiltrate secondary to an infectious process. Because MM, which is a disorder of the aged population, with its severe clinical course and heterogeneous symptoms, the diagnosis is difficult. The aim of this study was to investigate the causes, the frequency and the effects of prognosis of the pulmonary involvement in 38 patients with this disorder who were treated between January 1995 and April 2001 at the Department of Chest and Haematology-Oncology at Erciyes University Medical School. The patients with MM; 25 (66%) was male and 13 (34%) was female, and their mean age was 61 +/- 11 range 40-80 years. Of the 38 patients; 19 (50%) had thoracal involvement which included pulmonary involvement in 13 (%35) and thoracal bone invasion in 9 (24%). According to their clinical and radiological findings, the 13 cases with pulmonary involvement were evaluated and six had pneumonia, two had mass lesion, two had multiple nodular lesion, three had intersitial infiltration. Five (13%) of the patients with respiratory symptoms were admitted to the Chest Clinic. Malign plasma cell infiltration was detected by transthoracal lung biopsy in two patients with mass lesions, and with transbronchial lung biopsy in one patient with intersitial infiltration. The cases with pulmonary involvement were associated with progressive diseases, which included mainly renal failure and pathological bone fractures. Pulmonary involvement of MM is frequently associated with rapid progression of the disease and demonstrates the variability of roentgenographic manifestations. MM should be taken into consideration in the differential diagnosis of pulmonary infiltration in older patients with systemic complaints.

Adult↗

PubMedDate not supplied

Clinicopathologic features in two cases of multiple myeloma.

Multiple myeloma is a serious and fatal condition with various ocular manifestations. In two of these cases, pathologic findings included opaque ciliary body cysts, a ciliochoroidal effusion, retinal microaneurysms and hemorrhages, and detachment of both the sensory retina and the retinal pigment epithelium. In one case, a recanalized thrombus within a retrolaminar vein and direct continuity of a superonasal retinal detachment with a large pars plana cyst was observed. The proteinaceous material in the anterior chamber, ciliary body cysts, choroid and ciliary body, subretinal, and subretinal pigment epithelial areas was identified as immunoprotein using an immunoperoxidase technique.

Aneurysm↗

PubMed2004

An update of novel therapeutic approaches for multiple myeloma.

Multiple myeloma (MM) remains an incurable malignancy, despite conventional and high-dose therapies, and novel biologically based treatment approaches are urgently needed. Recent studies have characterized the molecular mechanisms by which MM cell/host bone marrow (BM) interactions regulate tumor cell growth, survival, and migration in the BM milieu. These studies have not only enhanced our understanding of disease pathogenesis, but they have also provided the framework for a new treatment paradigm targeting the MM cell in its BM microenvironment to overcome drug resistance and improve patient outcome. Clinical trials are confirming the remarkable activity and improved tolerability of some of the new agents identified through this paradigm, providing exciting evidence of translational success in MM.

Antineoplastic Agents↗

PubMed2005

The role of the bone marrow microenvironment in multiple myeloma.

Multiple myeloma (MM) is a malignant disease that results from an excess of monotypic plasma cells in the bone marrow (BM). This malignancy is characterised by complex karyotypic aberrancies. In 60% of all MM there are recurrent primary translocations involving the heavy chain gene locus. The MM cells strongly interact with the BM microenvironment, which is composed of endothelial cells, stromal cells, osteoclasts, osteoblasts, immune cells, fat cells and the extracellular matrix. This interaction is responsible for the specific homing in the BM, the proliferation and survival of the MM cells, the resistance of MM cells to chemotherapy, the development of osteolysis, immunodeficiency and anaemia. New therapeutic agents target both the MM, as well as the interaction MM cell - BM microenviroment.

Animals↗

PubMed2006

Biology and treatment of multiple myeloma.

Multiple myeloma (MM) is a B cell malignancy that accounts for 10% of all hematologic cancers. In recent years much has been learned regarding the biology of the myeloma clone; specifically on the chromosomal alterations that can be more frequently found and on the involved oncogenes. It has been also demonstrated that, in MM, bone marrow microenvironment, both in its cellular (stromal cells, osteoblasts, osteoclasts, endothelia) and protein (extracellular matrix) components, plays an important role in promoting growth and survival of malignant plasma cells. Much of this knowledge will be translated into a better patients treatment; although high-dose therapy programs can be considered the treatment of choice for patients aged 70 or younger, novel drugs, targeting MM clone in its microenvironment can be incorporated into these therapeutic programs improving response rate and patients survival.

Adolescent↗

PubMed2007

Towards a new age in the treatment of multiple myeloma.

Multiple myeloma (MM) is an incurable disease characterized by the proliferation of end-stage B lymphocytes (plasma cells, PCs). As a consequence of myeloma growth in the bone marrow, a number of signaling pathways are activated that trigger malignant PC proliferation, escape from apoptosis, migration, and invasion. Thanks to new insights into the molecular pathogenesis of MM, novel approaches aimed at targeting these abnormally activated cascades have recently been developed and others are under study. These strategies include the inhibition of membrane receptor tyrosine kinases, inhibition of the proteasome/aggresome machinery, inhibition of histone deacetylases, inhibition of farnesyltransferases, targeting of molecular chaperones, and others. We will herein review and discuss these novel biological approaches with particular emphasis on those based on biochemical pathways which drive cell signaling. By providing the rationale for innovative therapeutic strategies, the above mechanisms represent targets for new compounds being tested in the management of this disease.

Animals↗

PubMed2004

Molecular and clinical follow-up after treatment of multiple myeloma.

Multiple myeloma (MM) is a B cell malignancy characterized by accumulation of plasma cells (PCs) in the bone marrow. Traditional methods for the detection of minimal residual disease (MRD) measure the presence of monoclonal immunoglobulin protein secreted by the malignant PCs. However, changes in the level of MRD in MM may span 6 logs, and methods with a high sensitivity and dynamic range are necessary for quantitating MRD in MM. The two main technologies used in MRD detection are flow cytometry and patient-specific reverse transcription (RT) PCR. Patient-specific RT-PCR has high sensitivity and may be beneficial in monitoring patients receiving allogeneic transplantation. However, for the MRD evaluation of autotransplants, where few patients achieve molecular remission, flow cytometry monitoring seems to be sufficient.

Clinical Trials as Topic↗