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

Recent advances in the biology of multiple myeloma cell growth and survival have suggested new avenues for treatment and potential cure of this disease. Adhesion molecules on the myeloma cell surface mediate their localization in the bone marrow via binding to extracellular matrix proteins and stromal cells. Stromal cell to tumor cell contact and the secretion of transforming growth factor by tumor cells triggers interleukin-6 secretion from stromal cells and paracrine tumor cell growth. CD40 activation of myeloma cells changes their cell surface phenotype, triggers autocrine interleukin-6 secretion, and can regulate myeloma cell cycle in a p53-dependent fashion. Interleukin-6 is both a growth and survival factor for myeloma cells, and delineation of the signaling cascades mediating its effects permits the development of novel therapies either to interrupt growth or trigger apoptosis. New immune therapies offer the opportunity to treat minimal residual disease after stem cell transplantation, thereby improving outcome. Selected donor lymphocyte infusions after allografting and infusion of activated autologous T cells following autografting are examples of adoptive immunotherapy. Myeloma cell to dendritic cell fusions have been used in a vaccination strategy both to prevent and treat myeloma in an animal model, providing the rationale for similar clinical trials in humans. For the first time, a variety of novel treatment strategies derived from advances in understanding the disease pathogenesis offer the potential to achieve long-term disease-free survival in patients with multiple myeloma.
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PMID:Advances in the biology of multiple myeloma: therapeutic applications. 1052 90

The confirmation that most cancers express one or more molecular changes, which may act as tumour-associated antigens (TAA), combined with the knowledge that T lymphocytes recognize even single amino acid differences in MHC presented peptides has stimulated renewed clinical interest in immunotherapeutic strategies. Dendritic cells (DC) are now recognized as specialist antigen-presenting cells, which initiate, direct and regulate immune responses. Recent data suggest that DC are not recruited into, or activated by, cancers and that other abnormalities in DC function are associated with malignancy, including multiple myeloma. This provides a rationale for designing immunotherapeutic strategies, which exploit DC as nature's adjuvant either in vivo or in vitro. Low-grade lymphoma and multiple myeloma are slowly progressive malignancies, which generally express a unique immunoglobulin idiotype as a potential TAA. Data from animal models and clinical studies suggest that DC-based immunotherapy strategies, applied when the patient has minimal residual disease, may improve the long-term prognosis in these diseases.
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PMID:Dendritic cell immunotherapy for cancer: application to low-grade lymphoma and multiple myeloma. 1054 Feb 12

A sensitive, safe and cheap method to detect minimal residual disease (MRD) is here presented. The PCR-GS technique includes: (a) a fluorescent PCR for the IgH region with CDR3/JH consensus primers; (b) the electrophoresis on an automatic sequencer (ABI PRISM 310); (c) the analysis of results by the GeneScan program. A total of 72 samples were analysed: 34/49 B-cell Non-Hodgkin's Lymphoma (NHL) (69%), six out of seven Multiple Myeloma (MM) (86%), 1/2 Hodgkin's Disease (HD) and 4/4 Acute Lymphoblastic Leukaemia (ALL) were found to be positive, showing a monoclonal IgH rearrangement. The major bias of the PCR-GS method are the 21% of false negatives, but 13/15 negative patients carried t(14;18); consequently, the association of the evaluation by PCR assays of the IgH and BCL2/JH rearrangement allowed to detect a molecular marker of B-neoplasia in more than 94% of tested samples.
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PMID:An advantageous method to evaluate IgH rearrangement and its role in minimal residual disease detection. 1057 38

We have taken advantage of the selection power of phage display technology to define specific peptide mimotopes that recognize individual M-proteins, isolated from patients with multiple myeloma. Preferred amino acid motifs of phages binding to M-proteins were identified in 6/9 patients investigated. Chemically synthesized peptides, corresponding to the phage-displayed peptide inserts, were used to verify the specificity of binding in competition assays. The peptides were able to bind to the M-proteins, as well as the myeloma cells, with high sensitivity and specificity. Employing simple immunological techniques, < 0.01 g/l of M-protein could be quantified, suggesting a novel way for monitoring minimal residual disease in the production of guidelines for adjusting or reintroducing conventional chemotherapy. The peptide mimotopes defined by this technology may be useful as tumour-specific targeting agents and as a tool for purging cells in autologous bone marrow transplantation.
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PMID:Identification of patient-specific peptides for detection of M-proteins and myeloma cells. 1058 25

Dendritic cells (DCs) are extremely efficient antigen-presenting cells that are potent stimulators of both B and T cell immune responses. Although DCs are normally present in extremely small numbers in the circulation, recent advances in DC biology have made it possible to generate DCs in culture. DCs can be generated in vitro from various cellular sources including bone marrow, cord blood and peripheral blood. Although culture conditions are extremely diverse, the majority of protocols grow DCs in GM-CSF and either TNF-alpha and/or IL-4. The addition of other growth factors such as SCF and Flt-3 ligand can dramatically enhance DC recovery. It is important to appreciate that DC subsets have been identified. Thus, DC at different stages of maturation, based on phenotype and capacity to capture antigen, can be obtained depending on culture conditions. For clinical applications, DCs can be generated in serum-free media and cryopreserved for future clinical applications. The ability to obtain DCs in numbers suitable for manipulating immune responses has pushed DC-based immunotherapies into the spotlight for treatment of various malignancies, including multiple myeloma, a B cell malignancy that is presently incurable. Although high-dose chemotherapy and transplantation have improved complete remission rates and overall survival in myeloma, immunotherapeutic strategies are needed for the additional cytoreduction needed to achieve a cure. Because DCs specialize in antigen capture and are extremely potent at stimulating T cell responses, they are ideally suited for generating anti-myeloma T cell responses in vivo. Several studies have demonstrated that myeloma protein, also called idiotype (Id), is sufficiently immunogenic and can be used to generate in vivo T cell responses in myeloma patients. Clinical trials using Id-pulsed DCs as a vaccine to treat minimal residual disease or relapsed myeloma are currently underway. Feasibility studies indicate that antigen-pulsed autologous DCs can be used to elicit in vivo Id-specific T cell responses. Additional studies are needed to optimize current DC vaccination protocols and determine clinical benefits associated with this approach. It is hoped that, following conventional therapies, a combination of adoptive immunotherapeutic modalities such as DCs together with myeloma-specific T cells may lead to improved clinical responses in multiple myeloma, and ultimately lead to complete remission and cure.
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PMID:Dendritic cell biology and the application of dendritic cells to immunotherapy of multiple myeloma. 1071 54

BACKGROUND: The treatment of multiple myeloma, relatively stagnant for many years, appears to be entering a promising era for improvement. This paper reviews treatment interventions available for patients with multiple myeloma to indicate a standard approach and to evaluate the spectrum of current standard therapy. METHODS: The author reviews published literature on the treatment of multiple myeloma. Both journal articles and papers presented at national and international meetings are utilized. RESULTS: Intensive combination chemotherapy offers relatively modest improvement over standard melphalan plus prednisone, but the use of interferon for maintenance therapy lengthens response duration and possibly survival. High-dose chemotherapy with stem-cell transplantation is a relatively safe and effective treatment modality for patients under 70 years of age at first relapse. Studies in progress will determine its role in first response consolidation. Use of hematopoietic growth factors, prophylactic antibiotics, and bisphosphonate treatment of lytic bone disease has diminished disease morbidity. CONCLUSIONS: While cure of multiple myeloma remains elusive and 10-year survival is still uncommon, newer treatment approaches offer better control of disease manifestations and perhaps a real opportunity to prolong functional life. Future treatments that will address minimal residual disease may improve long-term survival.
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PMID:Management of Myeloma: Current and Future Approaches. 1076 Oct 55

Aiming to target the minimal residual disease in patients with multiple myeloma, a phase I/II single centre study was undertaken for feasibility and tolerance of intensive acute lymphoblastic leukaemia consolidation chemotherapy (ALL-IC) as part of a strategy for post-transplant consolidation targeted at pre-B cells. Seventeen newly diagnosed patients with myeloma (median age 55 years; 30-65) were initially treated with courses of infused cyclophosphamide, vincristine, adriamycin and methylprednisolone (C-VAMP) followed by melphalan 200 mg/m2(HDM) and peripheral blood stem cell rescue (PBSC). Forty-seven percent were in CR and the rest in PR after HDM. ALL-IC consisted of vincristine, daunorubicin, etoposide, cytarabine, 6-thioguanine and prednisolone given over 5 days. All patients became neutropenic (<0.5 x 109/l) at a median of 10 days (4-18) and one of the 17 patients (5.8%) died 15 days post ALL-IC of sepsis. A further four have died of relapse with an overall survival (OS) of 67% at 4 years. Two of nine patients in PR at the time of ALL-IC achieved CR. Matched-pair analysis of 34 control patients shows no difference for OS and event-free survival between ALL-IC and controls. We conclude that ALL-IC given to myeloma patients after HDM/PBSC is as safe as when used in ALL and warrants further assessment in randomised trials for myeloma.
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PMID:Acute lymphoblastic leukaemia-type intensive chemotherapy to eliminate minimal residual disease after high-dose melphalan and autologous transplantation in multiple myeloma - a phase I/II feasibility and tolerance study of 17 patients. 1080 62

The majority of patients with multiple myeloma (MM) have persistence of minimal residual disease (MRD), as determined by polymerase chain reaction (PCR) detection of clonal immunoglobulin H (IgH) gene rearrangements. As a result, PCR analysis has not provided clinically useful prognostic information in myeloma patients. Instead, quantitative PCR approaches are required to predict patient outcomes and assess response to novel treatment strategies. We adapted real-time PCR technology to quantify myeloma cells using the IgH rearrangement and then assessed the utility of this approach in 29 patients with myeloma who had undergone autologous stem cell transplantation. Because of the high cost of producing a specific reporting probe for each patient, H-chain V-region family-specific consensus probes were used in association with allele-specific oligonucleotides for PCR amplification. Because of the high frequency with which somatic hypermutation at the immunoglobulin locus occurs in MM, a number of mismatches occurred between the patient sequences and the consensus probe. However, construction of a limited number of probes allowed real-time PCR with a sensitivity of 10(-4) to 10(-5). To validate this method, we extensively evaluated assay accuracy and reproducibility. Results indicate that real-time PCR using consensus probes provides a feasible, accurate, and reproducible method for evaluating MRD in M M and possibly in other differentiated B-cell malignancies, and one that is less expensive than the use of patient-specific probes. This technique is being used to assess tumor depletion after immunologic purging and changes in tumor burden in patients undergoing stem cell transplantation and novel treatment approaches.
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PMID:Real-Time polymerase chain reaction of immunoglobulin rearrangements for quantitative evaluation of minimal residual disease in multiple myeloma. 1087 Nov 49

Multiple myeloma remains an incurable disease, and a new perspective on the approach to therapy is required. The aim of this review is to focus on a number of key areas where recent advances in the biology of the disease have not only yielded an understanding of the disease pathogenesis but have also suggested novel treatment approaches. Factors mediating myeloma cell growth, survival and the complex interaction of myeloma cells with the bone marrow microenvironment have provided a framework for the rational design of therapeutic agents. The development of such biologically based treatments which target both the tumour cell and the microenvironment, in order to achieve more complete and selective eradication of myeloma cells and the maintenance of minimal residual disease states, may ultimately lead to improved disease-free survival and potentially a cure.
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PMID:Novel therapeutic targets in multiple myeloma. 1090 89

The advent of new therapeutic approaches to multiple myeloma made necessary the introduction of novel methods for detection of minimal residual disease. Among others approaches residual disease can be detected by the immunofluorescence using flow cytometry. We have examined the co-expression of CD19, CD38, CD45, CD54, CD56, and CD138 molecules in cells of peripheral blood and bone marrow aspirates in patients with multiple myeloma by 3-color flow cytometry. For the detection and characterization of multiple myeloma cells, combinations of following antibodies were used: anti-CD19 FITC, anti-CD38 FITC, anti-CD38 PE, anti-CD54 FITC, anti-CD56 PE-Cy5, anti-CD45 PE, anti-CD45 PE-Cy5 (Immunotech) and anti CD138 PE (Serotec). The samples were analyzed using EPICS XL (Coulter) flow cytometer, and the analysis was based on at least 10,000 events. Samples from 17 patients were analyzed. The percentage of multiple myeloma cells ranged between 0.3% and 54.2% in bone marrow aspirates and between 0.0 and 11.8% in periferal blood. The expression of CD138, CD38, CD54 and CD56 molecules was found in 100%, 100%, 85% and 68% of examined cases, respectively. In our opinion, multiple myeloma cells are best characterized by following combinations of antibodies: CD38 FITC/CD138 PE/CD45 PE-Cy5, CD54 FITC/CD138 PE/CD56 PE-Cy5 or CD54 FITC/CD38 PE/CD 56 PE-Cy5. The identification of a malignant clone is the first and the most important step in the characterization of the disease, determination of its prognosis and the detection of residual disease after treatment. Three-color flow cytometry represents a method which can meet these goals.
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PMID:[Detection of multiple myeloma cells using multicolor immunofluorescence and flow cytometry]. 1095 45


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