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

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.
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PMID:The role of the bone marrow microenvironment in multiple myeloma. 1613 4

Immunodeficiency is a barrier to successful vaccination in individuals with cancer and chronic infection. We performed a randomized phase 1/2 study in lymphopenic individuals after high-dose chemotherapy and autologous hematopoietic stem cell transplantation for myeloma. Combination immunotherapy consisting of a single early post-transplant infusion of in vivo vaccine-primed and ex vivo costimulated autologous T cells followed by post-transplant booster immunizations improved the severe immunodeficiency associated with high-dose chemotherapy and led to the induction of clinically relevant immunity in adults within a month after transplantation. Immune assays showed accelerated restoration of CD4 T-cell numbers and function. Early T-cell infusions also resulted in significantly improved T-cell proliferation in response to antigens that were not contained in the vaccine, as assessed by responses to staphylococcal enterotoxin B and cytomegalovirus antigens (P < 0.05). In the setting of lymphopenia, combined vaccine therapy and adoptive T-cell transfer fosters the development of enhanced memory T-cell responses.
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PMID:Restoration of immunity in lymphopenic individuals with cancer by vaccination and adoptive T-cell transfer. 1627 72

Plasmablastic lymphoma is an aggressive diffuse large B-cell lymphoma classically arising in the oral cavities and jaws of individuals infected with the human immunodeficiency virus (HIV). More recently, cases of plasmablastic lymphoma have been identified in individuals negative for HIV. We report a case of plasmablastic lymphoma presenting as a rapidly expanding upper extremity mass in a 66-year-old individual negative for HIV. Aggressive multiple-agent chemotherapy resulted in a dramatic improvement of all symptoms. Increasing awareness of plasmablastic lymphoma in individuals who are HIV negative can allow for a better understanding of its clinical course and for specific chemotherapeutic regimens to be developed.
Clin Lymphoma Myeloma 2006 May
PMID:Plasmablastic lymphoma presenting as an arm mass in an individual negative for human immunodeficiency virus: a case report. 1679 82

Neutralizing antiviral antibodies (Abs) can hinder systemic virotherapy. Here, we used activated T cells as carriers to deliver oncolytic measles viruses (MV) to multiple myeloma xenografts in the presence of anti-MV antibodies (Abs). Virus-infected T cells expressing measles H/F fusogenic envelope glycoproteins could efficiently transfer MV infection by heterofusion, even after exposure to virus-inactivating anti-MV antisera. Severe-combined immunodeficiency (SCID) mice bearing subcutaneous or disseminated human myeloma xenografts were given MV-luciferase (MV-Luc) or MV-Luc-infected T cells intravenously. Indium111 labeling indicated that 1-2% of the virus-infected T cells trafficked to tumors. Preinfected T cells fused with tumor cells in vivo and transferred MV-Luc to tumor xenografts where intratumoral viral spread was monitored non-invasively using bioluminescent imaging. In mice passively immunized with high titers of measles immune serum, intravenous virus and cell delivery were both inhibited. Decreasing the amount of measles immune serum given to mice permitted tumor infection by virus-infected T cells and cell-free virus. In conclusion, virus-loaded T cells may facilitate systemic measles virotherapy in the presence of antiviral Abs and they warrant further investigation as potential MV cell carriers.
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PMID:Evaluation of T cells as carriers for systemic measles virotherapy in the presence of antiviral antibodies. 1705 Dec 48

The age-adjusted prevalence rate of monoclonal gammopathy of undetermined significance (MGUS) is three-fold higher in African Americans than whites. Similarly, there is a higher preponderance of multiple myeloma (MM) in African-American patients. Since the risk of progression of MGUS to MM is equal in both races, identification of exogenous and genetic risk factors of MGUS [such as genetic pre-disposition; diet; and chronic antigenic exposure related to sexually transmitted diseases, including human immunodeficiency virus (HIV) infection] is essential for unraveling the etiology of the racial disparity for MM. HIV infection, a well-documented risk factor for MGUS, is more frequent in African-American patients. Future epidemiologic studies dealing with plasma cell disorders should carefully examine the relationship between race, HIV infection status, prevalence of MGUS and its ultimate progression to MM.
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PMID:Higher prevalence of monoclonal gammopathy of undetermined significance in African Americans than whites--the unknown role of underlying HIV infection. 1712 99

Multiple myeloma is a clonal plasma cell malignancy within the bone marrow associated with bone loss, renal disease and immunodeficiency. Despite new insights into the pathogenesis of multiple myeloma and novel targeted therapies, the median survival remains 3-5 years. It is now well established that the intimate relation between the tumor cells and components of the microenvironment plays a key role in multiple myeloma pathogenesis. Specifically, tumor cells impact the bone marrow and thereby cause immune suppression and lytic bone lesions; conversely, components of the bone marrow provide signals that influence the behavior of multiple myeloma cells, including tumor cell growth, survival, migration and drug resistance. Important contributing effectors are tumor cell-stroma cell and cell-extracellular matrix contacts, the bone marrow vasculature, and a variety of cytokines and growth factors in the bone marrow milieu.
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PMID:Targeting the vascular endothelial growth factor pathway in the treatment of multiple myeloma. 1742 75

Plasmablastic microlymphoma (PML) is defined as the accumulation of monotypic but polyclonal plasmablasts in lymphoid tissues involved in human herpes virus 8 (HHV-8)-positive multicentric Castleman's disease (MCD). So far, the nature of this very rare condition remains poorly determined. In this study, we describe a human immunodeficiency virus (HIV)-seropositive patient who developed a PML in the setting of HHV-8-positive MCD. In contrast to the cases previously reported, most of the plasmablasts in our patient were localized within the germinal center (GC) of lymphoid follicles. These plasmablasts expressed the multiple myeloma-1/interferon regulatory factor-4 (MUM1/IRF4) protein as well as IgMlambda in a monotypic fashion. They did not show any immunoreactivity with antibodies directed against Pax-5, CD20, CD79a, CD10, CD30, CD23, CD138, epithelial membrane antigen (EMA) or BCL-6. These cells exhibited a high proliferation rate, expressed the HHV-8 latent nuclear antigen-1, and secreted the HHV-8 viral homologue of human interleukin-6. Polymerase chain reaction analysis did not demonstrate any clonal rearrangement of the genes coding for the heavy chain of the immunoglobulin. Moreover, no Epstein-Barr virus (EBV) RNA transcript could be found, using in situ hybridization. The present case illustrates that PML may arise within the GC of lymphoid follicles in the absence of EBV coinfection. In our opinion, PML occurring in MCD likely represents a variant of HHV-8-positive MCD in which lytic HHV-8 replication is particularly prominent, due to a local or systemic immune imbalance.
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PMID:Plasmablastic microlymphoma occurring in human herpesvirus 8 (HHV-8)-positive multicentric Castleman's disease and featuring a follicular growth pattern. 1761 57

Haematopoietic stem cell transplantation (HSCT) is now an established treatment fora number of non-malignant and malignant conditions. Bone marrow- or peripheral blood-derived allogeneic SCT from an HLA-identical sibling or matched unrelated donor cures more than half the patients with severe aplastic anaemia, thalassaemia major, congenital immunodeficiency diseases and genetic metabolic disorders. Among the malignant conditions, acute and chronic leukaemia, multiple myeloma, Hodgkin and non-Hodgkin lymphoma, and high risk neuroblastoma are important conditions that can be treated by HSCT. The major morbidities associated with HSCT are regimen-related toxicities, development of acute or chronic graft-versus-host disease (GVHD), failure of engraftment of the bone marrow and complications related to the immunodeficiency that occurs in the post-transplant period. Peripheral blood stem cells are now being used as an alternative to bone marrow stem cells for allogeneic HSCT and exclusively for autologous HSCT. Reduced intensity conditioning for allogeneic HSCT has resulted in a lower frequency and severity of GVHD and risk of infections. This has resulted in allogeneic HSCT being done in older patients and for those with co-morbid conditions. Patients with low grade Hodgkin and non-Hodgkin lymphoma, chronic lymphocytic leukaemia and multiple myeloma appear to benefit more with this approach. Prevention of acute GVHD while maintainingthe graft-versus-tumour effect and close monitoring of the kinetics of chimerism hold promise for improving the outcome of those receiving reduced intensity allogeneic HSCT. In recipients ofautologous HSCT, identification of patients at increased risk for relapse and use of agents (interferon, interleukin-2) post-transplant to augment the graft-versus-tumour effect are possible areas of further research.
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PMID:Haematopoietic stem cell transplantation: current status. 1786 17

Osteoprotegerin (OPG) acts as a decoy receptor for receptor activator of nuclear factor-kappaB ligand (RANKL) and TNF-related apoptosis-inducing ligand (TRAIL). OPG regulates bone remodeling and the immune response. The primary objective was to decipher, among human peripheral blood mononuclear leukocytes (PBML) that produce OPG, the subset(s) responsible for this synthesis and its regulation. To this end, normal human PBML and CD4-, 8-, 19-, 14-enriched subpopulations were studied in vitro for OPG synthesis. PBML were subjected to adherence and immunomagnetic separation, and OPG expression was analyzed by PCR, northern and western blotting, and ELISA. The antiapoptotic effects of OPG were studied on TRAIL-stimulated RPMI 8226 myeloma cells. OPG was time-dependently produced by primary CD4+ T lymphocytes exclusively. OPG secretion was upregulated by anti-CD3 antibody stimulation or incubation with interleukin (IL)-4, IL-1beta, TNF-alpha, GM-CSF, and vitamin D(3). In contrast, IL-10 inhibited the basal and IL-4-induced production of OPG by T cells. Conditioned media from activated T lymphocytes decreased TRAIL-induced apoptosis of RPMI 8226 cells. This effect was reversed by addition of RANKL to the T-cell conditioned media. As human immunodeficiency virus-1 (HIV-1) targets CD4+ T cells, we evaluated the effects of recombinant HIV-1 gp120 proteins on OPG synthesis. The gp120 from three different HIV-1 strains significantly reduced the basal output of OPG from T cells. Furthermore, all four protease inhibitors (PIs) used in highly active antiretroviral therapy decreased OPG synthesis by human blood T cells, nelfinavir being the most efficient PI. The simultaneous presence of an HIV-1 gp120 and a PI abrogated the basal output of OPG. In conclusion, these results highlight a new role for T lymphocytes involved in pathologies. Activated CD4+ T cells could, through OPG release, have a paracrine effect on adjacent cells and contribute to reduce the local process of bone remodeling and cellular apoptosis.
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PMID:Normal human primary CD4+ T lymphocytes synthesize and release functional osteoprotegerin in vitro. 1804 Feb 68

A 17-year-old Croatian boy with Nijmegen breakage syndrome (NBS) who developed diffuse large B-cell non-Hodgkin lymphoma is presented. The majority of the patients with this rare autosomal recessive disease are of Slavic origin and, in most of them, the disease is caused by NBS1 mutation 657del5, as was found in our patient. Nijmegen breakage syndrome is characterized by microcephaly, growth retardation, abnormal facial appearance, spontaneous chromosomal rearrangements, immunodeficiency, and a high predisposition to cancer development, predominantly lymphoma. Because of increased sensitivity to radiation therapy and chemotherapy, the treatment of malignancies in patients with NBS can be difficult. To our knowledge, our patient is the first with NBS reported in the literature who was successfully treated for diffuse large B-cell lymphoma with the anti-CD20 monoclonal antibody rituximab in addition to a modified dose of CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) chemotherapy. He has been in complete remission for 3 years after finishing the treatment.
Clin Lymphoma Myeloma 2007 Nov
PMID:Successful treatment of diffuse large B-cell non-hodgkin lymphoma with modified CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) chemotherapy and rituximab in a patient with Nijmegen syndrome. 1818 68


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