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)

A single rising dose tolerance trial of rDNA interferon-alpha 2 (IFN-alpha 2) was conducted in eight patients with the diagnoses of non-Hodgkin's lymphoma (NHL), multiple myeloma, and chronic lymphocytic leukemia (CLL). Patients received a total of six i.m. doses at weekly intervals as follows: 1, 3, 10, 30, 60, and 100 x 10(6) IU. Patients were monitored at each dose level for serum IFN activity, anti-IFN antibodies, immunomodulation, clinical toxicity, and response. All patients exhibited clinical toxicity, including fever, chills, fatigue, headache, anorexia, mild-to-moderate leukopenia, nausea, and vomiting. Toxicity was dose-related, with significant side effects occurring in all patients at levels of 10 x 10(6) IU and above and some evidence of tachyphylaxis at higher doses. All side effects, including leukopenia and thrombocytopenia, were of short duration and were resolved within 3-5 days. Fevers, rigors, myalgias, and fatigue were partially alleviated by premedication with acetaminophen or hydrocortisone. Pharmacokinetic data indicated mean peak serum IFN titers greater than 90 at a dose of 10 x 10(6) IU and greater than or equal to 200 at doses greater than or equal to 30 x 10(6) IU 8 h after injection. No anti-IFN antibodies were detected. However, the serum levels achieved at higher doses were not linear, possibly indicating in vivo degradation. Total T cells, B cells, monocytes, and T subsets monitored by flow cytometry with monoclonal antibodies remained essentially constant throughout the trial. Although some patients demonstrated minor augmentations of antibody-dependent cellular cytotoxicity (ADCC) and natural killing (NK) activity at the lowest IFN-alpha 2 doses, the majority of patients demonstrated decreases in NK activity after higher IFN doses. No correlation between immunomodulation and clinical response to IFN was observed. At higher dose levels, the predominant immunomodulatory effect of IFN-alpha 2 was suppression of NK, ADCC, and blastogenic responses to T-cell mitogens and recall antigens. B-cell functional deficits as well as radioresistant T-helper and radiosensitive T-suppressor function assessed in a pokeweed mitogen-driven immunoglobulin secretion assay appeared unaffected by IFN administration. One myeloma patient showed progression and was discontinued after 60 x 10(6) IU. There were four patients (3 NHL, 1 myeloma) who achieved partial remission (greater than or equal to 50% tumor reduction) and three (1 CLL, 2 NHL) who showed objective tumor responses of less than 50%. These data suggest that rDNA IFN-alpha 2 is well-tolerated and may have significant antitumor activity against lymphoproliferative malignancies. Clin
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PMID:Immunomodulation by recombinant interferon-alpha 2 in a phase I trial in patients with lymphoproliferative malignancies. 660 23

Thirty-three patients with advanced malignancy were treated with Wellferon. Doses ranging from 0.75 X 10(6) to 50 X 10(6) U were administered intramuscularly every 12 h for a 7-day course of therapy. Courses were repeated every 4 weeks as a function of tumor response. Toxicity resulted in fever, chills, malaise, leukopenia, thrombocytopenia, nausea and/or vomiting, diarrhea, hepatocellular damage, and, in a single case, gastrointestinal bleeding (which was a possible cause of patient death). Toxicity tended to increase with increasing dose, and 30 X 10(6) units every 12 h for 7 days was considered to be the maximally tolerated dose. Partial responses were seen in three patients with diagnoses of renal cell carcinoma, diffuse histocytic lymphoma, and Hodgkin's disease. Minimal responses were seen in four patients with diagnoses of chronic lymphocytic leukemia, multiple myeloma (two patients), and breast cancer. Positive response to therapy did not correlate with dose level.
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PMID:Phase I study of Wellferon (human lymphoblastoid alpha-interferon) as cancer therapy: clinical results. 664 35

Hemostasis was studied in 55 patients with myeloma, grouped in three groups according to the clinical stage of the disease. Thrombocytic adhesion, aggregation, activity of TF3 and TF4, of antithrombin III, FMDC level, FDP titre and fibrinolysis test were determined on the background of the screening coagulation tests. The studies were carried out before the treatment and were followed up after the therapeutic response or in the absence of improvement. Thirty per cent of the patients had manifestations of hemorrhagic diathesis, and 5 per cent - thromboembolism. Essential hemostatic deviations were found: progressive thrombocytopenia and thrombopathia and DIC syndrome that correlate with the stage of the disease, being most severe among the stage III patients. The patients that responded to the treatment had a great part of the hemostatic disorders corrected, and in case of no effect from the treatment - the deviations persisted, intensified and in 5 of the patients were responsible for the fatal end. The pathogenesis of the hemostatic deviations is complex and is associated with the characteristics of the basic disease and the concomitant complications.
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PMID:[Proceedings of the 7th Congress of Internal Medicine]. 665 83

A phase II trial was conducted to determine the clinical activity of amsacrine (m-AMSA) in patients with heavily pretreated solid tumors, myeloma, and lymphoma at the University of Arizona Cancer Center. Additionally, m-AMSA was evaluated at other Southwest Oncology Group institutions in breast cancer, myeloma, melanoma, and oat cell cancer of the lung. At a dose of 120 mg/m2 given iv every 28 days, 12 partial responses were observed in 221 patients evaluable for response. Some antitumor activity was observed in breast cancer (four responses of 65 patients), non-Hodgkin's lymphoma (three of nine), Hodgkin's disease (two of five), and sarcoma (two of 15). A partial response was also documented in one of two patients with cervical cancer. Among the 135 patients treated at the University of Arizona who were extensively evaluated for toxic effects, only myelosuppression and anemia were seen in a significant number of patients. At this dose and schedule, 29% of patients developed leukopenia of less than 3000 cells/mm3, 16% developed a thrombocytopenia of less than 100,000 cells/mm3, and 29% had an acute fall in hemoglobin of greater than or equal to 2 g/100 ml. In addition, two patients suffered grand mal seizures which were not clearly drug-related. These results suggest that further study of m-AMSA in lymphoma, sarcoma, and cervical cancer is warranted.
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PMID:Phase II evaluation of amsacrine (m-AMSA) in solid tumors, myeloma, and lymphoma: a University of Arizona and Southwest Oncology Group Study. 668 99

This paper over-viewed the clinical studies on various interferons including HLBI (human lymphoblastoid interferon), HuIFN-beta (human fibroblast interferon) and r-IFN-alpha A (recombinant leukocyte A interferon) which have been tried widely in Japan. These interferons have shown some antitumor effects on various malignancies such as malignant lymphoma, multiple myeloma, renal cell carcinoma, leukemias, brain tumors, malignant melanoma, mycosis fungoides and others. Adverse reactions included fever, general fatigue, leukopenia and thrombocytopenia, and abnormal liver function tests were experienced.
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PMID:[Effects of interferon on various malignancies]. 669 57

The Eastern Cooperative Oncology Group evaluated cyclophosphamide 600 mg/m2 intravenously daily X 4 (total dose each cycle 2400 mg/m2) as an aggressive approach to the treatment of patients with advanced multiple myeloma. The overall objective response rate is 43%. This includes a 38% response rate for all previously treated patients and a 29% response rate for patients refractory to prior therapy with cyclophosphamide. The objective response duration was 3 months and the survival of responding patients 9 months. A subjective response rate of 63% was observed, characterized by effective pain relief and improved performance. Sixty-nine percent of patients experienced leukocyte cell nadirs less than 500/mm2 with a mean time to marrow recovery of 17 days. Thrombocytopenia was less severe but required platelet transfusion in 43% of patients. Bone marrow toxicity was encountered in all patients, and death in aplasia is a significant risk. Strict adherence to entry criteria, and a systematic plan for hospitalization for antibiotic and blood component support is required for treatment with this regimen.
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PMID:High-dose cyclophosphamide. An effective treatment for advanced refractory multiple myeloma. 669 91

Five patients with multiple myeloma were treated with human lymphoblastoid interferon (HLBI). HLBI, 3 X 10(6) IU/day, was administered daily for more than two weeks by intramuscular injection. Out of four evaluable patients, a minor response was obtained in 3 patients. In these responders, one patient developed pleural effusion due to the infiltration of myeloma cells during the administration of HLBI, and drug resistance was observed in another patient during the re-administration of HLBI. Therefore, out of six evaluable courses, a minor response was obtained in 3 courses of HLBI treatment. No severe side effects were observed. Thrombocytopenia, general malaise, liver dysfunction and anorexia were the main reasons for discontinuation of HLBI administration. On the basis of the preliminary study, it is concluded that HLBI is worth trying in the management of refractory multiple myeloma.
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PMID:[Clinical effect of human lymphoblastoid interferon in patients with multiple myeloma]. 674 66

Platelet-associated IgG (PAIgG) was measured by a simple rapid nephelometric technique using washed solubilized platelets and commercially available, prestandardized reagents. Normal subjects with normal platelet counts had PAIgG levels of 2.1-6.7 fg/platelet. Subjects with idiopathic immune thrombocytopenic purpura (ITP) had levels of 7.2-43.3 fg/platelet. Ninety percent of ITP patients had values exceeding 2 SD units of the mean of normal subjects. Elevated values were also found in 17% of patients with recovered ITP, patients with SLE with and without thrombocytopenia, patients with thrombocytopenia occurring during septicemia, and patients with IGg myeloma. Results can be obtained within several hours of receipt of blood specimen, and are similar to the reports that used more complex techniques.
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PMID:A rapid quantitation of platelet-associated IgG by nephelometry. 680 16

130 patients with multiple myeloma were reviewed for a retrospective study of their classification according to Durie & Salmon. No significant difference was found in survival between patients in stages I, II and III (median survival 24.8, 32.1, and 17.3 months, respectively). Of the classical criteria affecting survival, only the Hb level showed any significant influence (P less than 0.04). In accordance with this finding, the survival time was much shorter (P less than 0.001) in patients with renal failure than in patients without (median survival 7.4 and 24.8 months, respectively); in addition, thrombopenia, fever, old age, and above all, the % of bone-marrow plasmocytes present, were shown to be decisive factors.
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PMID:Critical study of staging in multiple myeloma. 686 Apr 19

An autopsy study of 218 cases of lymphoproliferative disease was performed to establish the cause of death. It covered 144 cases of malignant nonHodgkin's lymphoma, 23 cases of Hodgkin's disease and 51 cases of myeloma. It was established that infection is by far the most frequent cause (34% of cases) followed by tumor invasion (11.5% of cases), hemorrhage (9% of cases) and other pathologies linked to the basic process (10% of cases). The proportion of patients who die from intercurrent illness is still considerable (62 cases, 28%). Infection is most often pulmonary or systemic; gram-negative bacteria play a predominant role. Toxicity of treatment is obvious in causing neutropenia and thrombocytopenia among other side effects with fatal consequences.
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PMID:[Causes of death in cases of lymphoma, myeloma and Hodgkin disease. Study of 218 cases]. 686 58


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