UMLS:C0026764 - FACTA Search

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

Severe bronchial hyperresponsiveness to methacholine developed after intravenous therapy with OK-T3 and IL-2 in a patient with multiple myeloma, in whom no factors known to be associated with bronchial hyperresponsiveness were present. A substantial increase and activation of peripheral T-lymphocytes was observed after immunotherapy. Bronchial responsiveness and lymphocyte subsets both returned to normal baseline values 2 months after the patient was shifted to subcutaneous low dose administration of IL-2. The strict association between peripheral T-lymphocytes activation and the development of bronchial hyperresponsiveness suggests a causal relationship.
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PMID:Reversible bronchial hyperresponsiveness induced by OK-T3/IL-2 administration in a patient with multiple myeloma. 857 20

The polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes (POEMS) syndrome is a rare multisystem disorder of obscure pathogenesis associated with osteosclerotic myeloma. Circulating levels of proinflammatory cytokines (tumor necrosis factor-alpha (TNF-alpha) interleukin-1 beta [IL-1 beta], IL-2, IL-6, and interferon-gamma [IFN-gamma]), anti-inflammatory cytokines (transforming growth factor beta 1 [TGF beta 1], IL-4, IL-10, and IL-13), the cytokine carrier protein alpha 2 macroglobulin, IL-1 receptor antagonist (IL-1ra), soluble TNF receptors (sTNFr) p55 and p75, and soluble IL-6 receptor (sIL-6r) were determined in 15 patients with POEMS syndrome and 15 with multiple myeloma. Patients with POEMS syndrome had higher serum levels of IL-1 beta, TNF-alpha, and IL-6 and lower serum levels of TGF beta 1 than did patients with multiple myeloma. Serum levels of IL-2, IL-4, IL-10, IL-13, IFN-gamma, alpha 2 macroglobulin, and sIL-6r were similar in both groups. IL-1ra and sTNFrs were increased in POEMS syndrome, but out of proportion to the increase of IL-1 beta and TNF-alpha. Serial evaluations in 1 patient showed that proinflammatory cytokine serum levels paralleled disease activity assessed by platelet count and neurologic involvement. Our results suggest that the manifestations of POEMS syndrome might be regarded as the result of a marked activation of the proinflammatory cytokine network (IL-1 beta, IL-6, and TNF-alpha) associated with a weak or even decreased (TGF beta 1) antagonistic reaction insufficient to counteract the noxious effects of cytokines.
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PMID:Overproduction of proinflammatory cytokines imbalanced by their antagonists in POEMS syndrome. 860 36

CD3 engagement has been used as a surrogate for antigen-specific stimulation to trigger T cell effector functions. Exogenous IL-2 has been used to prolong and amplify CD3-induced T cell activation. Previous studies have been shown that CD3 reactivity is increased in cancer patients with preactivated (> 10% HLA-DR+) T cells in the peripheral blood. In this study, we report 9 courses of a single infusion of anti-CD3 mAb (OKT3) followed by continuous infusion of intermediate dose IL-2 in 4 cancer patients [2 multiple myeloma (MM), 1 B-cell lymphoma (NHL), 1 metastatic melanoma (ME)] with advanced disease and > 10% HLA-DR+ T cells in the peripheral blood. An increase of lymphocytes, equally distributed between CD4+ and CD8+ subsets, was observed during treatment. Activation was phenotypically documented by the emergence of CD25+ cells in the peripheral blood. Unexpectedly, functional studies [including proliferation to mitogens (PHA, OKT3) and cytotoxicity assays (NK and LAK activities)] did not parallel phenotypic data and a slight decrease of all functions was observed after OKT3 and IL-2 treatment. OKT3 and IL-2 infusions were well tolerated and no limiting toxicity was observed. The treatment did not revert tumor progression in the 2 patients with progressive disease (NHL, ME) and had only minimal effects in the 2 MM patients with stable disease. These data indicate that the sequential administration of OKT3 and IL-2 had no anti-tumor activity in this small series of patients with advanced cancer who were selected for treatment because of an increased number of HLA-DR+ T cells in the peripheral blood. A discrepancy was observed between the emergence of CD25+ T cells and the clinical outcome.
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PMID:Clinical and immunological studies in advanced cancer patients sequentially treated with anti CD3 monoclonal antibody (OKT3) and interleukin-2. 872 15

The monoclonal antibody (MAb) G250 binds to a tumour-associated antigen, expressed in renal cell carcinoma (RCC), which has been demonstrated to be a suitable target for antibody-mediated immunotherapy. A bispecific antibody having both G250 and anti-CD3 specificity can cross-link G250 antigen-expressing RCC target cells with T cells and can mediate lysis of such targets. Therapy studies with murine antibodies are limited by immune responses to the antibodies injected (HAMA response), which can be decreased by using chimeric antibodies. We generated a chimeric bispecific G250/anti CD3 MAb by transfecting chimeric genes of heavy and light chains for both the G250 MAb and the anti-CD3 MAb into a myeloma cell line. Cytotoxicity assays revealed that the chimeric bispecific MAb was capable of mediating lysis of RCC cell lines by cloned human CD8+T cells or by IL-2-stimulated peripheral blood lymphocytes (PBLs). Lysis mediated by the MAb was specific for target cells that expressed the G250 antigen and was effective at concentrations as low as 0.01 microgram ml-1. The chimeric bispecific G250/anti-CD3 MAb produced may be an effective adjuvant to the currently used IL-2-based therapy of advanced renal cell arcinoma.
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PMID:Generation of chimeric bispecific G250/anti-CD3 monoclonal antibody, a tool to combat renal cell carcinoma. 879 76

During the last decade, the availability of large numbers of cytokines and growth factors has greatly favoured the use of biotherapies in several haematological disease. For MM, the majority of clinical studies have dealt with the use of IFN-alpha. From these studies it appears that IFN-alpha has a definite role in the treatment of MM especially in the setting of minimal residual disease, as maintenance therapy after response to conventional therapies or HDC followed by BMT procedures or PBSCI. Data on the use of EPO have consistently demonstrated the role of this growth factor in ameliorating the grade of anaemia as well as the quality of life of those MM patients whose disease is complicated by the presence of a severe or moderate anemia. Despite the large amount of experimental data indicating a role for IL-2 and IL-6 in controlling tumour growth, there are only a few clinical studies dealing with their use in MM. From these, it appears that IL-2 and anti-IL-6 antibodies should be further investigated as therapeutic tools useful in maintaining responses, because results show that they arrest tumour progression rather than aid, tumour regression. Finally, in the next years, there will be a wider diffusion of biotherapies in MM that should take into account the roles that IL-1 beta and TNF alpha play in myeloma cell proliferation and bone destruction and the finding that retinoic acid is capable of inhibiting the growth of human myeloma cells in vitro through modulation of IL-6 and its receptor.
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PMID:The role of biotherapies (interleukins, interferons and erythropoietin) in multiple myeloma. 884 74

In a group of 70 patients with multiple myeloma (MM), formed by 25 patients examined while establishing the diagnosis and 45 patients examined in different stages of the disease, the authors evaluated the relationship of the bromodeoxyuridine "labelling index" (BrdUrd-LI) of myeloma plasma cells assessed by the method of double immunofluorescence (using antibody BU-1) and selected laboratory indicators of the disease. In the whole group the median and mean values of BrdUrd-LI of myeloma plasma cells were 2.0 (0.6-4.4%) and 2.1 +/- 0.9%, in the group of 25 patients examined during diagnosis it was 1.8 (0.6-4.1%) and 1.9 +/- 0.9%, in the group of 45 patients examined during different stages of MM it was 2.4 (0.6-4.4%) and 2.4 +/- 0.8%. Neither in the whole group nor in the sub-groups any statistically significant correlations were found between BrdUrd-LI values and the degree of anaemia, values of S-creatinine, S-MIG, S-albumin, S-B2M, S-ferritin, S-thymidine kinase, S-IL-6, S-IL-2, S-kIL-2R, the percentage ratio of myeloma plasma cells in bone marrow and the synthetic index of myeloma plasma cells paraprotein.
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PMID:[The bromodeoxyuridine index in multiple myeloma. I. Relation with selected laboratory indicators of the disease]. 892 21

It is known that anti-alpha(1 --> 3) dextran antibodies of BALB/c mice are ordinarily of distinctive idiotypes (Id), one of which is the individual idiotype (IdI) that is represented by J558 or M104E to myeloma protein. In the present study, we established T cell line of Th1 type which recognized the Id of anti-alpha(1 --> 3) dextran antibody, and investigated its specificity and functions. The T cell line, named J-2R, had a phenotype of CD3+ CD4+ CD8- and expressed alphabeta-T cell receptors (TcR). J-2R proliferated in response to J558 in an I-Ed-restricted manner but did not respond to M104E which had substitution at amino acids 100 and 101. We confirmed that J-2R recognized J558 IdI, using synthetic peptides corresponding to two serial amino acid residues, Arg100 and Tyr101, spanning the J558 IdI in the third hypervariable region (hv3) of the heavy chain. alpha(1 --> 3) dextran-binding B cells which were isolated from dextran-immunized mice activated J-2R, but B cells from nonimmune mice did not. J-2R produced IL-2, IFN-gamma and IL-6, but did not produce IL-4, IL-5, or IL-10. Furthermore, J-2R inhibited the growth of J558 myeloma cells inoculated to the syngeneic mice in vivo. These findings suggest that Id-specific CD4+ T cells, J-2R, are involved in Id network and may play a role in vivo. J-2R is useful for analysis of the role of the Id-specific helper T cells in immune network because J558 IdI is frequently present on anti-alpha(1 --> 3) dextran antibodies.
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PMID:Establishment and characterization of an anti-idiotypic CD4+ CD8- T cell line to murine anti-alpha(1 --> 3) dextran antibody. 895 18

Tumour-specific CD4+ T helper (Th) and CD8+ T cytotoxic (Tc) cells may participate in the control and eradication of tumour cells. In the present study, idiotype-specific stimulation of CD4+ and CD8+ blood T cells from patients with monoclonal gammopathy of undetermined significance and patients with untreated multiple myeloma stage I was examined. Activation was measured in the CD4+ and CD8+ subsets enriched by magnetic microbeads as the incorporation of 3H-thymidine and the secretion of interferon (IFN)-gamma, interleukin (IL)-2 and IL-4 by single cells using the enzyme-linked immunospot assay. Idiotype-specific T cells were found in four of seven patients. Stimulation was mainly confined to the CD4+ subset in three of the four responding patients. This type of response was major histocompatibility complex (MHC) class II restricted as it could be inhibited by monoclonal antibodies against MHC class II (HLA-DR), but not against class I (HLA-ABC) molecules. Idiotype-specific CD8+ T cells were also demonstrated in these patients although at a lower frequency. One patient showed a strong and dominating activation of CD8+ T cells which could be blocked by antibodies against HLA-ABC but not against HLA-DR. Idiotype-specific CD4+ or CD8+ T cells were mainly of the type-1 subsets as judged by their secretion of IFN-gamma and IL-2. Thus, this study provides evidence for the presence of idiotype-specific and MHC-restricted CD4+ and CD8+ T cells of the type-1 subsets in patients with monoclonal gammopathies. Such T cells with the potential to control the growth of tumour B cells may be a suitable target for immunotherapeutic interventions in patients.
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PMID:Idiotype-specific T lymphocytes in monoclonal gammopathies: evidence for the presence of CD4+ and CD8+ subsets. 902 23

The success of autologous stem cell transplantation (ASCT) for hematologic malignancy is limited largely by a high relapse rate. It is postulated that IL-2 administered after ASCT may eliminate minimal residual disease and thereby reduce relapses. A phase I/II study was performed to identify a regimen of IL-2 (Chiron) that could be given early after ASCT in phase III trials. In the phase I study, beginning a median of 46 days after ASCT for hematologic malignancy, cohorts of three to four patients received escalating doses of 'induction' IL-2 of 9, 10, or 12 x 10(6) IU/m2/day for 4 or 5 days by continuous i.v. infusion (CIV), followed by a 4-day rest period, and then 1.6 x 10(6) IU/m2/day of maintenance IL-2 by CIV for 10 days. The maximum tolerated dose (MTD) of induction IL-2 was 9 x 10(6) IU/m2/day x 4. In the phase II study, 52 patients received the MTD. Eighty percent of patients completed induction IL-2. Most patients exhibited some degree of capillary leak. One patient died of CMV pneumonia and one died of ARDS. Maintenance IL-2 was well tolerated. In the phase I/II study, 16 of 31 patients with non-Hodgkin lymphoma (NHL), 3/8 with Hodgkin disease (HD), 4/17 with AML, and 4/5 with ALL remain in CR. Two of six multiple myeloma (MM) patients remain in PR. Although the regimen of IL-2 identified had significant side-effects in some patients, it was well tolerated in the majority of patients. Phase III prospectively randomized clinical trials are in progress to determine if this IL-2 regimen will decrease the relapse rate after ASCT for AML and NHL.
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PMID:Interleukin-2 after autologous stem cell transplantation for hematologic malignancy: a phase I/II study. 905 8

Cytogenetics in multiple myeloma (MM) cases are generally difficult to perform due to the low proliferation index of malignant plasma cells (PC) in most cases. Although IL-6 and GM-CSF stimulate the in vitro proliferation of malignant plasma cells, their usefulness for improving cytogenetic results in multiple myeloma patients remains questionable, because results which compare various culture conditions in a sufficient number of patients are not available. By using a miniaturized karyotypic method, we compared in 30 multiple myeloma patients the number and percentage of clonal abnormal mitoses obtained from 3 and 6 d bone marrow cultures performed without or with two combinations of cytokines: IL-6 + GM-CSF or IL-6 + GM-CSF + IL-2 + IL-4 + TNFalpha. The percentage of patients with an abnormal karyotype, which varied with the Durie and Salmon stage of the disease, as well as the type of numerical and structural karyotypic abnormalities that we detected, were in agreement with published results. The detection of clonal karyotypic abnormalities was better after 3d of culture without cytokine than in all other culture conditions. The higher percentage of patients at all stages of MM with an abnormal karyotype in our study (76.6%) than in previous ones (20% to 60%) is largely explained by the large number of mitoses analysed in six different culture conditions due to the use of a miniaturized karyotypic method.
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PMID:Cytogenetic study of 30 patients with multiple myeloma: comparison of 3 and 6 day bone marrow cultures stimulated or not with cytokines by using a miniaturized karyotypic method. 905 68

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