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

Monoclonal IgG gammopathy of the lambda light-chain type was detected in a 51-year-old woman who had unexplained fever, muscle fatigue, and myalgia. One year later, myasthenia gravis was diagnosed. There was no evidence of myelomatosis or other malignancy. On the assumption that her M-component (gammopathic paraprotein) was related to myasthenia, she was treated with melphalan and cyclophosphamide, but her clinical condition was not improved. Despite therapeutic trials of other agents and a time course of 6 years, the quantity of the M-component remained unchanged. Serum AChR antibody activity was not located in the paraprotein peak. The findings do not support a relationship between the M-component and myasthenia gravis.
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PMID:Myasthenia gravis and monoclonal IgG gammopathy. 10 88

From June 1988 to November 1990 the Southwest Oncology Group initiated nine protocols for the phase II evaluation of recombinant human tumor necrosis factor alpha (rhuTNF alpha) in cancer patients. Patients with diverse metastatic malignancies including breast, colon, gastric, pancreatic, endometrial, and bladder cancers, as well as multiple myeloma and various sarcomas received 150 micrograms/m2 of rhuTNF alpha daily for 5 days every other week. Of 147 patients entered in the study, 127 were eligible and were evaluated for toxicity and response. Of 124 patients known to have completed treatment, 92 (74%) went off study for progression, 21 (17%) for toxicity, and 12 (10%) for other causes, mainly that of worsening medical condition. Thirteen percent of patients experienced grade 4 or fatal toxicity. The most serious toxicities were pulmonary failure and coagulopathies. The predominant grade 3 toxicities were symptomatic (chills, fever, malaise, headache, myalgia, and nausea or vomiting). Only one partial remission was seen in a patient with metastatic bladder cancer lasting 4 months (rate 0.8%, exact 95% confidence interval 0-4%). At the study dose and schedule, rhuTNF alpha does not appear to have significant antitumor activity. The biological basis for this finding is discussed.
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PMID:Phase II studies of recombinant human tumor necrosis factor alpha in patients with malignant disease: a summary of the Southwest Oncology Group experience. 176 76

The case of 65 year old woman with progressive enlargement and "wooden" induration of the pelvic girdle and thigh muscles due to an amyloid infiltration is reported. Muscle changes appeared two years after a diagnosis of myeloma with free lambda light chains. The patient complained of muscle pain, lassitude and weakness. Macroglossia was present. Skeletal muscle (vastus lateralis) contained large amounts of amyloid substance and showed type 2B atrophy. There was no fiber type grouping. Some amyloid deposits abutted on the muscle fiber, destroyed the basal lamina and sarcolemma, but never infiltrated it. Besides the amyloid phagocytosis by macrophages, a relationship between amyloid filaments and fibroblasts was present. Another non-congophilic substance was revealed using the Avidin-Biotin peroxidase complex to localize lambda light chains by light microscopy and corresponded to a granular substance in electron microscopy. Clinicopathological results are discussed with a review of thirteen similar cases previously reported.
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PMID:[Pseudo-hypertrophic pelvi-crural amyloid myopathy in lambda light-chain myeloma. Clinical, morphological and immunocytochemical study]. 311 Sep 2

Blood and/or bone marrow cells from patients with hematological malignancies, chronic lymphocytic leukemia (CLL), chronic myeloid leukemia in blastic phase, acute lymphoid leukemia, acute myeloid leukemia, prolymphocytic leukemia, multiple myeloma and myelofibrosis, were incubated with Lonidamine at different concentrations (50, 100 and 160 micrograms/ml) for 1-2 h. B lymphocytes of CLL had the highest sensitivity to the drug: a decrease of more than 30% in the viable nucleated cells was recorded in 8 out of 10 experiments. Subsequent in vivo studies were performed to investigate the effectiveness of Lonidamine in the treatment of CLL. The drug was administered orally for a period of 7 days to 19 selected patients, both previously treated and untreated, in different stages of the disease. Only 5 patients responded: 2 of them had a significant decrease (greater than 30%) in the lymphocyte count, and the remaining 3 showed an appreciable reduction of the spleen (1 case) and of the lymph node size (2 cases). Generalized myalgia was the most common side effect induced by Lonidamine.
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PMID:Lonidamine in the treatment of chronic lymphoid leukemia. 671 3

The widespread use of alpha-interferon (IFN-alpha) therapy in different diseases draws attention to its side effects, such as autoimmune-related diseases, especially thyroid autoimmune dysfunctions. Data about hepatitis and nonhematologic neoplasia are available, while data about hematologic malignancies are fragmentary. We studied the incidence of autoimmune-related disturbances and thyroid dysfunctions in 54 consecutive patients suffering from hematologic malignancies, treated with recombinant human IFN-alpha for a mean time of 15.9 +/- 8.9 months. Our results minimize the incidence of autoimmune dysfunctions in hematologic malignancies as side effects of IFN-alpha therapy. We registered the appearance of autoantibodies in only 3 females (5% of total): 2 patients (1 affected with essential thrombocythemia and one with multiple myeloma) presented antithyroglobulin antibodies with no clinical symptoms; 1 patient, affected with essential thrombocythemia, developed antinuclear antibodies with arthralgia and myalgia. ARA criteria for systemic lupus erythematosus were not fulfilled but the therapy had to be interrupted. No patient developed thyroid dysfunction. In patients with hematologic malignancies, the dosage and the duration of IFN-alpha treatment do not seem to influence the appearance of autoantibodies, while female sex appears to be a risk factor.
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PMID:Autoimmune thyroid dysfunctions in hematologic malignancies treated with alpha-interferon. 772 47

Osteolytic bone destruction, caused by the aberrant production and activation of osteoclasts, results in significant morbidity for patients with multiple myeloma (MM). Pamidronate [(3-amino-1-hydroxypropylidene)-1,1-bis-phosphonate] inhibits osteoclastic activity and reduces bone resorption. A potency of zoledronic acid (2-[imidazol-1-yl]-1-hydroxyethylidene-1,1-bisphosphonic acid, a new third generation bisphosphonate, as inhibitor of resorption was 850-fold greater than pamidronate, as was shown in preclinical models of bone resorption. Randomized, double-blind study was conducted to compare the efficacy and safety of zoledronic acid and pamidronate for treating myeloma bone disease. Since March 1999 the efficacy and safety of pamidronate and zoledronic acid is evaluated in MM patients all receiving anti-myeloma chemotherapy acc. to VMCP/VBAP alternating regimen. Nine patients with stage III myeloma and osteolytic lesions (3 female, 6 male, median age 57 years, range 52-67, with monoclonal protein: IgG-7, IgA-2) were randomly assigned (1:1:1 ratio) to treatment with either 4 or 8 mg of zoledronic acid via 15-minute intravenous infusion or 90 mg of pamidronate via 2-hour intravenous infusion every 3 to 4 weeks for 12 months. All patients have received 500 mg of calcium supplements and 500 IU of vit.D, orally, once daily, for the duration of administration of study medication. In extension phase of the study (June 2000-April 2002) patients did not received bisphosphonates. In 7 patients 18 cycles of assessed treatment was administered to each of them and one patient received 16 cycles. One patient died after receiving of 12 pamidronate therapy cycles at 11 month of the trial duration (and at 49 month since MM diagnosis and anti-tumour treatment). The patient's death occurred during the progression of plasma cell proliferation due to acute left ventricle cardiac failure. During the 12-month-period of bisphosphonate treatment skeletal related events (SRE) and progression of osteolysis occurred with the same frequency in 3 treatment groups. One patient experienced spinal cord compression and received radiation to bone and 2 patients experienced vertebral fracture. Time from study entry to the first SRE was 304 days in pamidronate and 366 and 392 days in 4 and 8 mg zoledronic acid group, respectively. The skeletal morbidity rate was identical in all treatment groups. Single hypocalcemic events occurred in 2 patients, mild hypertransaminasemia was observed in 3, worsening of renal function parameters in 2 patients (transient in one of them). Muscular pain and fever up to 39 degrees C (transient and self-limiting "flu-like" symptoms) occurred in 6 patients after several or some dozens of hours from study drug administration. Adverse events were similar in nature and frequency with zoledronic acid and pamidronate and were experienced by a similar proportion of patients in each treatment group. Median time of patient's observation duration after completing of administered treatment with zoledronic acid and pamidronate amounts to 20 months. At present actual median survival time of analysed patients since MM diagnosis is 42 months, since the beginning of treatment with pamidronate and zoledronic acid--33 months, and since completing treatment--20 months and is similar in 3 treatment groups. As was shown in our single center study in MM patients the safety and efficacy of pamidronate 90 mg and zoledronic acid 4 mg and 8 mg in monthly i.v. infusion are comparable. Thus the recommended dosage of zoledronic acid is 4 mg administered as a 15 minute i.v. infusion at intervals of 3 to 4 weeks.
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PMID:Comparative evaluation of safety and efficacy of pamidronate and zoledronic acid in multiple myeloma patients (single center experience). 1266 77

Bortezomib, as a single agent and in combination with dexamethasone, was examined as first-line treatment in 32 consecutive patients with untreated symptomatic multiple myeloma. Patients received bortezomib 1.3 mg/m(2) for a maximum of six 3-week cycles; oral dexamethasone 40 mg was added if a less than partial response (PR) was achieved after two cycles or a less than complete response (CR) was achieved after four cycles. The response rate (CR + PR) was 88%, with undetectable paraprotein (CR) in 6%, and detectable by immunofixation only in 19% [near (n)CR]. All 32 patients completed the first two cycles of bortezomib alone, of whom 3% achieved CR, 9% nCR, and 28% PR. Ten patients received single-agent bortezomib on study, and dexamethasone was added in 22, leading to 15 improved responses. The most common adverse events >/=grade 2 included sensory neuropathy (31%), constipation (28%), myalgia (28%) and fatigue (25%). Sensory neuropathy grade 2 or 3 was reversible within a median of 3 months in five of 10 patients. Bortezomib treatment did not affect stem cell mobilization in eight or transplantation in six patients. Bortezomib alone or in combination with dexamethasone is an effective induction therapy with a high CR and nCR rate and manageable toxicities in previously untreated patients with myeloma.
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PMID:Bortezomib therapy alone and in combination with dexamethasone for previously untreated symptomatic multiple myeloma. 1595 4

High-dose chemotherapy and autologous peripheral blood progenitor cell transplantation is an effective treatment for multiple myeloma. Progenitor cells are generally mobilised into the peripheral blood by administration of filgrastim. Pegfilgrastim is a covalent conjugate of filgrastim with a longer half-life. The results of a phase II study of pegfilgrastim, administered as a single injection to mobilise autologous peripheral blood progenitor cells in patients with multiple myeloma, is reported. All patients (n = 19) received 12 mg of pegfilgrastim. Leukaphaeresis was started when the peripheral blood CD34(+) count was >0.015 x 10(9)/l. Daily, leukaphaeresis was performed until the target progenitor cell dose was obtained. The median number of leukaphaeresis procedures required to collect the target CD34(+) cell dose was 2 (range 1-5). A median of 8.4 x 10(6) CD34(+) cells/kg (range 4.1-15.8) was collected. The most common toxicity was bone pain/myalgia. Sustained haematological recovery occurred in all the patients who underwent high-dose chemotherapy followed by autologous peripheral blood progenitor cell transplantation with pegfilgrastim-mobilised cells. A single fixed dose of pegfilgrastim was effective in mobilising adequate peripheral blood progenitor cells in patients with multiple myeloma. The efficacy and toxicity profile was similar to that described with filgrastim treatment.
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PMID:Fixed-dose single agent pegfilgrastim for peripheral blood progenitor cell mobilisation in patients with multiple myeloma. 1668 42

The toll-like receptor (TLR) 7 agonist 852A, a small-molecule imidazoquinoline, stimulates plasmacytoid dendritic cells to produce multiple cytokines. We conducted a Phase II study of 852A in patients with recurrent hematologic malignancies. The primary objective was assessing the activity of 852A administered subcutaneously twice weekly for 12 weeks. Secondary objectives were assessing the safety of 852A and its ability to activate the immune system with prolonged dosing. Patients with relapsed hematologic malignancies of any age with adequate organ function were eligible. Patients initiated dosing at 0.6 mg/m(2) twice weekly and escalated by 0.2 mg/m(2) after every two doses as tolerated to a target dose of 1.2 mg/m(2) . Patients with responses or stable disease were eligible for additional cycles. Seventeen patients (15 males) entered the study: 6 with AML, 5 ALL, 4 NHL, 1 Hodgkin's lymphoma, and 1 multiple myeloma. The mean age was 41 years (12-71 years). The median number of prior chemotherapy regimens was 5 (range = 1-14). Thirteen patients completed all 24 injections. Grade 3-4 toxicities included nausea, dyspnea, fever, myalgia, malaise, and cough. Responses included one complete response (ALL), one partial response (AML), two stable disease (AML and NHL), and 9 progressive disease. This is the first in-human hematologic malignancy trial of a subcutaneously (SC) delivered TLR7 agonist using a prolonged dosing schedule. 852A was safely administered up to 1.2 mg/m(2) twice weekly with evidence of sustained tolerability and clinical activity in hematologic malignancies. Systemic TLR agonists for the treatment of hematologic malignancies warrant further study.
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PMID:Prolonged subcutaneous administration of 852A, a novel systemic toll-like receptor 7 agonist, to activate innate immune responses in patients with advanced hematologic malignancies. 2271 33

Plasmacytoma is a rare disease, which afflicts 2 to 3 people per every 100,000 of the general population. Solitary plasmacytoma accounts for 5% of the plasma cell neoplasm. Solitary plasmacytoma of the bone appears more vividly in the axial skeleton (25-60%), which has the red marrow and usually affects the thoracic vertebrae. We report a case of 54-year-old man who has a chest pain on the right side. After being treated for the muscle pain, his symptoms of pain were changed into weakness and allesthesia. We checked the MRI and found a mass lesion in the T5 vertebra, but there were no significant laboratory findings, in blood and urine samples. Finally, he got an operation due to the aggravation of the weakness. The result of biopsy indicated that it was a solitary plasmacytoma of the spine. After 5 months later, the weakness and allesthesia had disappeared.
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PMID:Atypical thoracic solitary plasmacytoma. 2318 43


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