Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Traditionally, response to treatment in multiple myeloma has been measured by the serum or urinary paraprotein and the percentage of plasma cells in the bone marrow. The use of allogeneic and autologous transplantation has increased the complete response rate and overall survival in patients with myeloma, and in order to assess the effects of such treatments accurately more sensitive methods for assessing residual disease have been introduced. The aim of this chapter, therefore, is to describe the available techniques to assess response, monitor residual disease and predict relapse in myeloma. The traditional techniques of paraprotein measurement using electrophoresis and immunofixation are compared with more sensitive approaches involving the polymerase chain reaction for detecting rearrangements of the immunoglobulin heavy-chain region and flow cytometry for detecting malignant plasma cells. Emphasis is placed on the advantages and disadvantages of each method and its utility in the clinical setting.
 ...
PMID:Minimal residual disease monitoring in multiple myeloma. 1198 24

Immune responses towards malignant plasma cells have clearly been demonstrated in the course of monoclonal B cell dyscrasias and shown to be mostly specific for idiotypic determinants of the monoclonal immunoglobulin (Ig). These responses are specifically efficient against lymphoma cells expressing a membrane form of the monoclonal Ig. In myeloma, such immune responses are often weak and a number of strategies are currently assayed in order to boost the cell-mediated responses against the secreted monoclonal Ig. The use of cytokines promoting Th1 responses could be helpful for the induction of anti-tumour immunity and the control of residual disease in patients treated with myeloablative therapy, and such strategies need to be evaluated. In a light chain myeloma model where the monoclonal Ig can only be secreted, we tried to induce protective immune responses through immunization of animals with transfected malignant plasma cells. An expression plasmid encoding GM-CSF and IL-12 proved to be highly efficient for the induction of both cytotoxic and proliferative responses after immunization of animals with transfected and irradiated tumour cells. Anti-tumour immunization according to this protocol was successful in protecting 93.4% of the animals against a subsequent tumour challenge.
 ...
PMID:GM-CSF and IL-12 production by malignant plasma cells promotes cell-mediated immune responses against monoclonal Ig determinants in a light chain myeloma model. 1216 80

This study examined the safety of adding 153Sm lexidronam to standard conditioning regimens in patients undergoing stem cell transplantation for marrow based haematological malignancies in whom total-body irradiation as part of conditioning was desirable but not feasible. Ten such patients were enrolled, seven with multiple myeloma. An escalating regimen of 19-45 GBq of 153Sm lexidronam was added 12-14 days prior to the standard transplantation regimen. Evaluation parameters included time to engraftment, status at day +100 by International Bone Marrow Transplant Registry (IBMTR) criteria and toxicity during this period. Absorbed marrow radiation doses were estimated using the MIRDOSE 3 program. No adverse events were attributable to 153Sm lexidronam. Of the seven patients with multiple myeloma, four achieved complete response, two partial response, and another had stable monoclonal band at 3 months post-transplant. One patient with Refractory Anaemic with Excess Blasts in transformation (RAEBt) died of a presumed fungal infection, whilst another with acute myeloid leukaemia relapsed, dying at day +153. A patient with low-grade lymphoma showed no evidence of residual disease at day +100. The total marrow absorbed dose was estimated to be 0.7+/-0.2 mGy x MBq(-1). Regional uptake was markedly non-uniform with poor uptake in the appendicular skeleton. Dose-limiting toxicity was not attained. At the activities used 153Sm lexidronam was not associated with additional toxicity in this population. Adequate absorbed radiation dose to appendicular marrow is unlikely to be deliverable by this approach alone.
 ...
PMID:153Sm EDTMP for bone marrow ablation prior to stem cell transplantation for haematological malignancies. 1241 39

The aim of this work was to evaluate the long-term immunological and clinical impact of idiotype (Id) vaccination in multiple myeloma (MM) patients in first remission after high-dose chemotherapy. A total of 15 patients received a series of subcutaneous (s.c.) injections of autologous Id, conjugated to keyhole limpet hemocyanin (KLH) and in association with low doses of GM-CSF. The median duration of follow-up was 110 months from diagnosis. The vaccine induced immune responses that lasted almost 2 years after the end of treatment. Antibody responses included anti-KLH IgM and IgG (90% of patients), anti-KLH IgE (30%), anti-GM-CSF IgG (20%), anti-Id IgG (20%), and anti-Id IgE (30%). Id-specific delayed type hypersensitivity skin tests were positive in 85% of tested patients. Following vaccination, a progressive recovery of T-cell receptor (TCR) diversity was observed and the loss of oligoclonality was significantly correlated with the remission duration. Although Id/KLH conjugates did not eliminate the residual tumor burden, the median progression-free survival, and overall survival were 40 and 82 months, respectively. A retrospective case-matched analysis showed similar results in patients treated with IFN-alpha alone or in association with steroids. This vaccine formulation can overcome Id-specific immune tolerance by inducing clinical responses that are worthy of further investigation.
 ...
PMID:Long-term follow-up of idiotype vaccination in human myeloma as a maintenance therapy after high-dose chemotherapy. 1457 32

Multiple myeloma (MM) is a malignant clonal neoplasm of plasma cells of B-lymphocyte origin that commonly results in overproduction of large amounts of monoclonal immunoglobulins. Important advances in the therapeutic management of this disease in the past decade have resulted in higher rates of durable complete remission, prolonged event-free survival, and improved overall survival. Clearer understanding of the effects of abnormal plasma cells on bone has led to therapeutic approaches that help prevent vertebral body fractures. Current imaging technologies and, in particular, survey marrow studies with magnetic resonance (MR) imaging have improved detection of the extent and location of disease in MM patients. In newly diagnosed cases, MR surveys of the axial skeleton accurately demonstrate the extent of disease-diffuse or focal involvement-and the presence of associated compression fractures and cord compression. After treatment, MR images show the effects of treatment and the presence of residual disease. Multiple sites of focal bone lesions detected on MR studies allow a more appropriate choice of biopsy site than the usual random iliac marrow biopsy. Use of MR to determine biopsy sites and computed tomographic guidance for biopsy performance have increased the safety and accuracy of sampling. These biopsies have resulted in increased identification of cytogenetic abnormalities, particularly the presence of chromosome 13 deletion, which is a grave prognostic indicator in MM.
 ...
PMID:Multiple myeloma: clinical review and diagnostic imaging. 1561 90

We combined the specificity of tumor-specific antibody with the chemokine function of interferon-gamma inducible protein 10 (IP-10) to recruit immune effector cells in the vicinity of tumor cells. A novel fusion protein of IP10-scFv was constructed by fusing mouse IP-10 to V(H) region of single-chain Fv fragment (scFv) against acidic isoferritin (AIF), and expressed in NS0 murine myeloma cells. The IP10-scFv fusion protein was shown to maintain the specificity of the antiAIF scFv with similar affinity constant, and bind to the human hepatocarcinoma SMMC 7721 cells secreting AIF as well as the activated mouse T lymphocytes expressing CXCR3 receptor. Furthermore, the IP10-scFv protein either in solution or bound on the surface of SMMC 7721 cells induced significant chemotaxis of mouse T cells in vitro. The results indicate that the IP10-scFv fusion protein possesses both bioactivities of the tumor-specific antibody and IP-10 chemokine, suggesting its possibility to induce an enhanced immune response against the residual tumor cells in vivo.
 ...
PMID:A novel fusion protein of IP10-scFv retains antibody specificity and chemokine function. 1521 58

To improve the antimyeloma effect of donor lymphocyte infusion (DLI) after allogeneic stem cell transplantation in multiple myeloma, we investigated in a phase 1/2 study the effect of low-dose thalidomide (100 mg) followed by DLI in 18 patients with progressive disease or residual disease and prior ineffective DLI after allografting. The overall response rate was 67%, including 22% complete remission. Major toxicity of thalidomide was weakness grade I/II (68%) and peripheral neuropathy grade I/II (28%). Only 2 patients experienced mild grade I acute graft versus host disease (aGvHD) of the skin, while no grades II to IV aGvHD was seen. De novo limited chronic GvHD (cGvHD) was seen in 2 patients (11%). The 2-year estimated overall and progression-free survival were 100% and 84%, respectively. Adoptive immunotherapy with low-dose thalidomide and DLI induces a strong antimyeloma effect with low incidence of graft versus host disease.
 ...
PMID:Low-dose thalidomide and donor lymphocyte infusion as adoptive immunotherapy after allogeneic stem cell transplantation in patients with multiple myeloma. 1529 62

Standard fluorescence in situ hybridization (FISH) easily detects nonrandom karyotypic abnormalities in multiple myeloma (MM) at disease presentation, when tumor burden is high. In contrast, the detection of residual MM using the standard 200 unselected nonmitotic nuclei FISH approach correlates poorly with residual disease detected by morphology, flow cytometry, immunohistochemistry, or reverse-transcription polymerase chain reaction (RT-PCR). We have used sequential May-Grunwald Giemsa stain to identify plasma cell populations, followed by FISH analyses (target FISH or T-FISH) to detect immunoglobulin heavy-chain gene (IGH) rearrangements, 13q or 17p deletions, or hyperdiploidy. In this study, 115 samples were collected from 100 patients with MM regardless of treatment status. In this proof-of-principle prospective study, T-FISH detected MM in 52 samples (45%), a percentage similar to that obtained by pathology. Disease detection increased from 5.6% with standard FISH to 48% with T-FISH, and cell culture experiments showed that T-FISH consistently detected a clonal abnormality at dilutions of 10(-3). In five patients, T-FISH further identified myelodysplastic-associated karyotypic changes restricted to myeloid cells. Our observations suggest that T-FISH identifies cell lineage involvement of cytogenetic abnormalities, improves detection of low-level or residual MM, and may define the coexistence of hematologic karyotypic changes in individual patients.
 ...
PMID:Targeting plasma cells improves detection of cytogenetic aberrations in multiple myeloma: phenotype/genotype fluorescence in situ hybridization. 1579 56

Multiparametric immunophenotyping of multiple myeloma (MM) and other plasma cell (PC) dyscrasias represents an attractive approach not only for research purposes but also in clinical practice. Based on well-established antigenic patterns, discrimination between myelomatous and normal PCs can be easily achieved in various types of samples, and this can be particularly valuable for the differential diagnosis between MGUS and MM and for monitoring residual disease in the latter. In addition, immunophenotyping may be an alternative and more reproducible method than morphology for evaluating PC infiltration, as well as for specifically analyzing DNA content and the cell-cycle distribution of different subsets of PCs. Despite the widespread use, standardization of methods and protocols still remains a challenge. In this chapter, we describe in detail the protocols and precise instructions for specimen collection, sample preparation, together with the methods for staining PCs and flow cytometry, data acquisition, and data analysis, including the more recent developments in the field. We highlight the most frequent limitations, and provide troubleshooting and practical recommendations that could help to solve them. The goal of this chapter is to emphasize the relevance of methodological issues in order to obtain reproducible and high-quality results regarding the phenotypic analysis of PCs.
 ...
PMID:Immunophenotyping of plasma cells in multiple myeloma. 1596 91

Immunoglobulin idiotypes (Id) of malignant B cells are tumor-specific antigens that may be targeted for immunotherapy. Id-directed immunotherapy by immunization with autologous Id has been initiated in clinical trials to control residual disease in B-cell lymphoma and multiple myeloma. The effector mechanisms responsible for destruction of B-cell tumors are a controversial issue. The authors show that vaccination with Id-pulsed dendritic cells (DCs) or with soluble Id-KLH in adjuvant induced immune responses that eliminated both B-cell lymphoma and myeloma in tumor-bearing mice; however, the two vaccination regimens resulted in distinct immune responses. Whereas soluble Id plus adjuvant induced high levels of anti-Id antibodies, the Id-pulsed DCs did not induce anti-Id or any antitumor antibodies. Immunization with Id-pulsed DCs induced a significant increase in the frequency of Id-reactive T cells. Depletion studies in DC-vaccinated mice showed that the predominant effector cells responsible for tumor rejection were of the CD8 subset. The finding that DC-based Id vaccines elicit tumor protection, which is entirely based on cell-mediated effector mechanisms, is of particular importance for plasma cell tumors because these tumors do not express Id on the surface and hence do not bind anti-Id antibodies.
 ...
PMID:B-cell lymphoma and myeloma protection induced by idiotype vaccination with dendritic cells is mediated entirely by T cells in mice. 1611 2


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>