SEARCH · PubMed Health

Results for “MULTIPLE MYELOMA”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources

PubMed2004

Immunomodulation of multiple myeloma.

Multiple myeloma is a multi-process disease, and these different processes are responsible for the reduced sensitivity to chemotherapy and radiotherapy, hence the relapse and refractory nature of multiple myeloma. Emphasis is now placed on the hypothesis that myeloma cell growth, inhibition of apoptosis and drug resistance are dependent on immunomodulatory cytokines such as IL-6 and pro-angiogenic factors such as VEGF. In addition to its anti-angiogenic effects, the immunomodulatory properties of thalidomide make it a possible therapy for patients with advanced multiple myeloma. This has lead to the clinical development of a number of immunomodulatory thalidomide analogues (IMiDs) which are more potent and have less side effects than the parent drug, thalidomide. In the August 15(th) issue of Journal of Clinical Oncology, Schey SA et al. suggested that an IMiD (CC-4047) maybe efficacious due to T-cell co-stimulation, and safe in patients with relapsed or refractory multiple myeloma. This article demonstrates a supporting role for IMiDs as immunomodulatory adjuvant therapy.

Angiogenesis Inhibitors↗

PubMed2005

8-Amino-adenosine induces loss of phosphorylation of p38 mitogen-activated protein kinase, extracellular signal-regulated kinase 1/2, and Akt kinase: role in induction of apoptosis in multiple myeloma.

Multiple myeloma is a slowly proliferating B-cell malignancy that accumulates apoptosis-resistant and replication-quiescent cell populations, posing a challenge for current chemotherapeutics that target rapidly replicating cells. Multiple myeloma remains an incurable disease in need of new therapeutic approaches. The purine nucleoside analogue, 8-amino-adenosine (8-NH2-Ado), exhibits potent activity in preclinical studies, inducing apoptosis in several multiple myeloma cell lines. This cytotoxic effect requires phosphorylation of 8-NH2-Ado to its triphosphate form, 8-amino-ATP, and results in a concomitant loss of endogenous ATP levels. Here, we show the novel effect of 8-NH2-Ado on the phosphorylation status of key cellular signaling molecules. Multiple myeloma cells treated with 8-NH2-Ado exhibit a dramatic loss of phosphorylation of several important signaling proteins, including extracellular signal-regulated kinase 1/2, p38 mitogen-activated protein kinase, and Akt kinase. Cells depleted of ATP independent of 8-NH2-Ado do not exhibit the same decrease in phosphorylation of vital cellular proteins. Therefore, the significant shifts in endogenous ATP pools caused by 8-NH2-Ado treatment cannot account for the changes in phosphorylation levels. Instead, 8-NH2-Ado may influence the activity of select regulatory protein kinases and/or phosphatases, with preliminary data suggesting that protein phophatase 2A activity is affected by 8-NH2-Ado. The distinctive effect of 8-NH2-Ado on the phosphorylation status of cellular proteins is a novel phenomenon for a nucleoside analogue drug and is unique to 8-NH2-Ado among this class of drugs. The kinetics of 8-NH2-Ado-mediated changes in phosphorylation levels of critical prosurvival and apoptosis-regulating proteins suggests that the modulation of these proteins by dephosphorylation at early time points may be an important mechanistic step in 8-NH2-Ado-induced apoptosis.

Adenosine↗

PubMed1995

Use of clodronate in multiple myeloma.

Multiple myeloma is characterized by bone disease including osteoporosis, osteolytic lesions, pathological fractures and hypercalcaemia leading to pain, immobilization and decrease in the quality of life. Clodronate, a bisphosphonate, has been shown to be effective in the treatment of hypercalcaemia in patients with multiple myeloma. In addition, clodronate reduces the progression of osteolytic lesions and the amount of vertebral fractures and may also relieve pain in these patients. Recent studies suggest that oral clodronate should be considered in the adjunctive treatment of all patients with active multiple myeloma independently of the presence of bone lesions at diagnosis. Due to its safety and efficacy, clodronate seems to have gained an important role in the management of patients with multiple myeloma.

Antimetabolites↗

PubMed1992

[Recent biological and therapeutic advances in multiple myeloma].

Multiple myeloma still remains a fatal disease. However, in the last months new biological and clinical informations have been provided about this disease. In particular, the immunophenotype of myeloma cells seems indicate, in some patients, a clonal involvement of a stem cell in the pathogenesis of mieloma. Moreover, new biological insights concerning the cytokine network, have revealed a probable effect of some cytokines, such as IL6, IL3, IL4. Finally, new insights in the biology of multiple myeloma have been provided by studies of molecular biology and flow cytometry. As for therapy, the best conventional induction treatment still remains to be defined. In the last years, the increased use of alpha Interferon and new therapeutic modalities, such as transplantation procedures in multiple myeloma, open new hopes toward a cure of this disease. Therefore, in the future a better knowledge of the multiple myeloma biology, associated with a wider use of new effective therapeutic approaches will certainly improve the natural course of this disease.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1990

The effect of ranitidine on cellular immunity in patients with multiple myeloma.

Multiple myeloma is characterized by an increased susceptibility to infections and to other malignancies. In a double-blind, placebo-controlled study the potential impact of immunomodulation by ranitidine was studied in 20 patients with multiple myeloma. Three patients were untreated, while 17 after previous cytotoxic therapy were in a stable phase of their disease. All were without clinical signs of infections and at that time had not been treated with other immunomodulating agents. The patients were randomized to oral ranitidine 300 mg twice a day for 21 days or placebo, and several immunological parameters related to multiple myeloma were studied. The blood monocyte chemotactic response was improved in patients treated with ranitidine, and superoxide anion production increased from 2.02 nmol/min to 3.86 nmol/min (median values), while it was unchanged in patients given placebo (2.19-2.25 nmol/min) (P less than 0.005 between groups). Among ranitidine-treated patients spontaneous NK cell activity was unchanged, while in vitro interleukin-2- and interferon-alpha-stimulated NK cell activity decreased (P less than 0.03, respectively). As production of oxygen radicals constitutes an important mechanism of monocyte killing activity against microorganisms and probably against malignant cells, it is suggested that ranitidine may be of beneficial impact in the treatment of multiple myeloma.

Adjuvants, Immunologic↗

PubMed2006

New questions about transplantation in multiple myeloma.

Multiple myeloma is now the most common indication for autologous stem cell transplantation (ASCT) in North America, with over 5,000 transplants performed yearly (Center for International Blood and Marrow Transplant Research [CIBMTR] data). While the role of ASCT as initial therapy in multiple myeloma has been established by randomized studies, newer therapies are challenging the traditional paradigm. The availability of novel induction agents and newer risk stratification tools, and the increasing recognition of durability of remissions are changing the treatment paradigm. However, even with arduous therapy designed to produce more complete remissions-for example, tandem autologous transplants-we have seen no plateau in survival curves. A tandem autologous procedure followed by maintenance therapy may be performed in an attempt to sustain remission. Sequential autologous transplants followed by nonmyeloablative allotransplants are pursued with the hope of "curing" multiple myeloma. We examine how the key challenges of increasing the response rates and maintaining responses are being addressed using more effective induction and/or consolidation treatments and the need for maintenance therapies after ASCT. We argue that given the biologic heterogeneity of multiple myeloma, risk-adapted transplant approaches are warranted. While the role of curative-intent, dose-intense toxic therapy is still controversial, conventional myeloablative allogeneic transplants need to be reexamined as an option in high-risk aggressive myeloma, given improvements in supportive care and transplant-related mortality.

Humans↗

PubMed2006

Case report: amyloid tumors in a case of non-secretory multiple myeloma.

Multiple myeloma (MM) is a neoplastic disorder characterized by proliferation of a single clone of plasma cells derived from B cells, which proliferates in the bone marrow and frequently invades the adjacent bone, producing skeletal destruction that results in bone pain and fractures. Patients with MM can furthermore present with anemia, hypercalcemia and renal failure. Non-secretory multiple myeloma (NSMM) is characterized by the absence of a monoclonal (M) protein in both the serum and urine. The reported incidence is 1-5% of all multiple myeloma cases. Development of amyloid tumors in NSMM has been described in the literature only occasionally. The clinical features of a 49-year-old female patient with NSMM and amyloid tumors in the breast, lung and rib are presented in this report. Conventional histology, Congo red staining with and without potassium permanganate pretreatment, aldehyde bisulfite-toluidine blue (ABT) reaction, sialic acid specific topo-optical reaction, toluidine blue topo-optical reaction as well as immunohistochemistry were performed. An attempt is made to explain the lack of monoclonal immunoglobulins in the serum and urine, although extensive organ amyloidosis of AL type (kappa-light chains) has been found. It is assumed that the plasmocytic plasma cells possess an excretory mechanism, which allows the pathologic immunoglobulins to be secreted either as amyloid proteins polymerizing into amyloid fibrils, or as immunoglobulin fragments that are subject to degradation as soon as they are excreted out of the tumor cell. In this paper, we review the occurrence of amyloid tumors in non-secretory multiple myeloma and, in a single case report, we confirm the existence of carbohydrate residues, including sialic acids and sulfated GAGs, in amyloid deposits.

Amyloid↗

PubMed1983

Psychiatric complications of multiple myeloma.

Multiple myeloma is an uncommon cancer, but of eight patients with multiple myeloma admitted to a general hospital over 5 months, five had psychiatric illness, and four of the five had delirium. Consulting psychiatrists should be aware of the common occurrence of impaired cognition in patients with multiple myeloma.

Aged↗

PubMed2004

[Involvement of apoptosis and proinflammatory cytokines in the pathogenesis of anemia in multiple myeloma].

Multiple myeloma is a neoplasmatic disease of the hematopoietic system which constitutes about 10% of all hematological proliferations. Anemia is a common symptom of myeloma, especially in patients with advanced disease, and its severity correlates with the clinical stage of myeloma. There are several factors involved in the pathogenesis of anemia in multiple myeloma: infiltration of the bone marrow with monoclonal plasma cells, inadequate secretion of erythropoietin, shortened erythrocyte survival time, dysregulated iron metabolism, impaired marrow function due to proinflammatory cytokine secretion, and interaction between erythroblasts and malignant plasma cells. Recent findings indicate an important function of apoptosis in regulating physiological erythropoiesis. In physiological conditions some erythroblasts undergo apoptosis, which is induced by proteins belonging to the TNF family, i.e. Fas(CD95), FasL(CD95L),and TRAIL (TNF-related apoptosis inducing-ligand) with its receptors--DR4 (Death Receptor 4), and DR5 (Death Receptor 5). Expression of Fas, DR4, and DR5 is detected on the cell membrane of erythroblasts in all stages, whereas FasL and TRAIL are present only in more mature erythroblasts. Interaction of mature erythroblast FasL+/TRAIL+ with immature erythroblast FasL-/TRAIL--results in apoptosis of the immature cell, which contributes to the down-regulation of physiological erythropoiesis. The expression of proteins involved in erythropoiesis regulation is controlled by erythropoietin (EPO), which decreases erythroblast susceptibility to FasL and TRAIL stimulation and prevents apoptosis. On the other hand interferon gamma (IFN-gamma) and tumor necrosis factor (TNF) increase Fas expression on erythroid cells and enhance their apoptosis. Malignant plasma cells show increased expression of FasL and TRAIL and decreased expression of Fas, which make them more resistant to apoptotic signals. FasL+/TRAIL+ plasmocytes are involved in anemia pathogenesis in multiple myeloma patients by inducing apoptosis of erythroid cells. Monoclonal plasmocytes also secrete numerous cytokines involved in plasma cell growth, bone marrow neovascularisation and anemia.

Anemia↗

PubMed2006

Current status of new drugs for the treatment of patients with multiple myeloma.

Multiple myeloma, a malignant disorder of plasma cells, is the second most common haematological malignancy. Although treatable, multiple myeloma remains incurable in virtually all cases, with a median survival of 3-4 years. Fortunately for patients with this disease, traditional treatment paradigms have been challenged with the emergence of a number of new therapies entering clinical practice over the last 6 years. In this review, we focus on the use of thalidomide (Thalidomide Pharmion; Boulder, CO, USA), lenalidomide (Revlimid; Celgene Corporation, Summit, NJ, USA) and bortezomib (Velcade; Janssen Pharmaceutica N.V., Belgium) in the treatment of myeloma. We present the current clinical experience with respect to efficacy and toxicity of these promising new agents and how the incorporation of these drugs with traditional therapies may improve the outcome for patients with multiple myeloma.

Antineoplastic Agents↗

PubMedDate not supplied

Recent progress in multiple myeloma.

Multiple myeloma is recognized as a neoplasm of phenotypically mature plasma cells which produces a variety of clinical symptoms related both to tumour infiltration of the bone marrow and cytokine production. The latter results in bone disease and a complex interactive network between plasma cells, marrow stromal cells and other hematopoietic cells. This serves to sustain the myeloma proliferative pool and promote maturation and secretion of monoclonal immunoglobulin. Whereas the recognizable tumour cells in myeloma are the most mature B cells, early lymphoid cells are involved in the disease and probably represent the proliferative pre-plasma cell compartment. The definition of the myeloma 'stem cell' remains controversial, but our understanding of early pre-plasma cell differentiation in multiple myeloma has been aided by studies on normal non-neoplastic equivalents. Techniques like high resolution flow cytometry, flow cytometric DNA analysis and improvements in our ability to obtain karyotypic data in multiple myeloma will improve our understanding of myeloma cell biology, hopefully yielding new prognostic information. Finally, improvements in assessing prognosis will help identify patients whose survival with standard therapy is limited and who may require innovative or aggressive treatment protocols. These individuals must be separated from patients who either require no initial therapy or who are likely to have good outcomes with standard approaches.

Antigens, Surface↗

PubMed1993

[Interferon therapy in multiple myeloma].

Multiple myeloma is a B-cell malignancy characterised by a clonal expansion of plasma cells. Prognosis of the disease can be based upon clinical stage and biological features of myeloma cells as well as of their products. Cytostatic therapy is a standard in the treatment of multiple myeloma. A new aspect is the therapeutic administration of recombinant interferons (rIFNs). Some experience has been gathered that chemotherapy-induced remissions (plateau phase) can be maintained by IFN-therapy. In induction therapy, IFN in combination with cytostatic agents has some therapeutical relevance, either. The administration of IFN in the treatment of multiple myeloma represents a new therapeutic strategy.

Biomarkers, Tumor↗

PubMed2004

The current status of hematopoietic stem cell transplantation for multiple myeloma.

Multiple myeloma is often successfully controlled with conventional chemotherapy, but complete remissions are uncommon and cure is rare. High-dose therapy followed by autologous or allogeneic stem cells, employed for the treatment of multiple myeloma in the past 20 years, is promising as a means to increase remission rates and improve survival. Autologous transplants have not always demonstrated survival benefits in randomized studies because most of the patients transplanted relapse, while patients given conventional therapy can receive salvage transplants when they relapse. Efforts to improve the results of autologous transplant include targeted radiation, cytoprotective agents, tandem transplants, or post-transplant immunotherapy. Only allogeneic hematopoietic stem cell transplantation is potentially curative, due to a graft-versus-myeloma effect. While patients who receive either allogeneic or autologous stem cell transplants for multiple myeloma have similar 3-5 year survival, only allograft recipients appear to enjoy long-term disease-free survival. High transplant-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.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2002

[The role of human herpesvirus-8 infection in the pathogenesis of multiple myeloma].

Multiple myeloma is a B-cell neoplasm characterized by abnormal proliferation and accumulation of monoclonal plasma cells in the bone marrow. Recently some laboratories have detected human herpesvirus-8 (HHV-8) DNA sequences in bone marrow dendritic cells from myeloma patients. It has been suggested that the cytokines expressed by HHV-8 gene, such as vIRF, vIL-8R and vIL-6, may play a role in the pathogenesis of multiple myeloma. However, the majority of European investigators failed to find evidence to confirm this observation. It remains unclear whether HHV-8 is consequentially associated with myeloma or only a regional opportunistic infection. Controversy still focuses on the role of specific HHV-8 strains involved in pathogenesis of multiple myeloma and causality between the

Cytokines↗

PubMed2001

[Role of thalidomide in the treatment of multiple myeloma].

Multiple myeloma is a relatively common hematologic malignancy with no definitive treatment available. Although, therapy may include allogenic bone marrow transplantation, high-dose ablative chemotherapy followed by bone marrow or peripheral stem cell transplantation, melphalan/corticosteroid therapy, alpha-interferon treatment, and combined cytostatic chemotherapy, currently none of these alternatives offers cure for the disease. Thalidomide is an infamous molecule for its teratogenicity, yet it possesses potent immunomodulatory, anti-angiogeneic and, in higher concentrations, direct anti-myeloma-cell properties. At present, the drug is only approved for the treatment of erythema nodosum of leprosy, however, there are several preliminary results that show clinical efficacy in multiple myeloma. This drug has especially potent anti-myeloma effects in combinations with dexamethasone and certain cytostatic chemotherapeutic agents. The effects are evident both in polyresistant, and relapsing myeloma, a form with no accepted effective treatment options. In this paper, the fundamental molecular and cellular effects of thalidomide are summarized then the most important clinical studies with thalidomide are reviewed. It is the authors' hope that thalidomide will soon be a full member of the medical arsenal in the fight against multiple myeloma.

Antineoplastic Agents↗

PubMed2002

Molecular mechanisms of novel therapeutic approaches for multiple myeloma.

Multiple myeloma remains largely incurable despite conventional and high-dose therapies, and so novel biologically based treatment approaches are urgently required. Recent studies have characterized the molecular mechanisms by which multiple myeloma cell-host bone-marrow interactions regulate tumour cell growth, survival and migration in the bone-marrow microenvironment. These studies have not only enhanced our understanding of disease pathogenesis, but have also provided the framework for a new treatment model that targets the multiple myeloma cell in its bone-marrow microenvironment to overcome drug resistance and improve patient outcome.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1995

The clonogenic precursor cell in multiple myeloma.

Multiple myeloma is characterized by the monoclonal expansion of plasma cells in the bone marrow. Although the predominant cell type is the plasma cell, the initial oncogenic transformation is considered to take place in a more immature B cell. There is still much controversy about this precursor cell type. Phenotypic analysis of bone marrow and peripheral blood revealed that in multiple myeloma a great diversity exists in the phenotype of the cells considered to be involved. Because of the lack of a myeloma specific genetic lesion it is very difficult to trace back the cell in which the transforming event, leading to multiple myeloma, took place. The only real clonal marker is the idiotype of the immunoglobulin molecule expressed by the myeloma cells. With recombinant DNA technology it is now possible to produce clonal markers for each individual myeloma patient which recognize only the immunoglobulin genes expressed by the myeloma cell and its precursors. The sequences of these myeloma immunoglobulin genes do reveal a lot of information about the stage in the B-cell differentiation pathway in which the oncogenic event might have taken place. The presence of somatic mutations in a non-random fashion without intraclonal variation leads to the conclusion that the precursor myeloma cell could not possibly be a pre-B cell or stem cell but has to be a mature B cell that has been in contact with antigen and has past through the phase of somatic mutation, like a memory B cell or plasmablast.(ABSTRACT TRUNCATED AT 250 WORDS)

B-Lymphocytes↗

PubMedDate not supplied

[Management of multiple myeloma].

Multiple myeloma (MM) remains an incurable malignancy, the median overal survival of patients receiving conventional chemotherapy being only 36-60 months. MGUS can evolve to MM in a percentage of 0.6-3% per year. The therapeutic management of multiple myeloma (MM) for the last several decades has mainly involved regimens based on use of glucocorticoids and cytotoxic chemotherapeutics. Melphaln and Prednisone (MP) are recognized as the classic treatment of MM. In patients candidate to bone marrow transplantation, VAD (Vincrisrine, Adriamicin, Dexamethasone) regimen is more indicated because it does not cause stem cell injury. High dose chemotherapy and and Autologous stem cells transplantation represent the best treatment for patients with MM who are younger than 65 years and free of severe comorbidities. Thalidomide alone or in combination with steroids has significant activity in multiple myeloma (MM). After the role of thalidomide in the management of patients with advanced or refractory MM had been established, many studies are evaluating the efficacy and toxicity of thalidomide as first-line therapy for patients with newly diagnosed disease. Recent studies have enhanced our understanding of disease pathogenesis and also provided the framework for a new treatment paradigm targeting the MM cell in its bone marrow 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.

Humans↗