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)

Multiple myeloma (MM) is characterized by an increased susceptibility to infections and to other malignancies. Selected related immune functions were studied. Spontaneous and interleukin-2-stimulated natural killer (NK) cell activities were normal in 19 patients with MM compared with 62 controls. In contrast, interferon-stimulated NK cells had a significantly lower increase in activity in MM than in controls. The normal improvement in lytic NK cell activity after addition of indomethacin to the mononuclear cell cultures (to inhibit prostaglandin-mediated suppression) was not observed in cultures from MM patients. As reported for other lymphoproliferative disorders, the levels of soluble interleukin-2 receptors in serum were significantly higher in MM (600 U/ml median value) compared with controls (317 U/ml median value), P less than 0.0001, and the concentration of interleukin-2 receptors was significantly correlated with the concentration of monoclonal immunoglobulin in serum. Blood monocyte chemotactic responsiveness was significantly lower in MM patients with both zymosan-activated serum and f-Met-Leu-Phe as cytotaxins, suggesting reduced ability to accumulate at inflammatory foci. In contrast, release of reactive oxygen radicals, believed to be associated with the killing ability of monocytes, was normal after in vitro stimulation.
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PMID:Immune dysfunction in multiple myeloma. Reduced natural killer cell activity and increased levels of soluble interleukin-2 receptors. 203 17

Pentostatin, a novel inhibitor of adenosine deaminase, has shown activity in various lymphoid malignancies of both the T and B cell lineage. This agent has unique side effects and in general myelosuppression has been mild. Interferon has both antiviral and antineoplastic properties. This agent has shown activity in hairy cell leukemia, chronic granulocytic leukemia, low grade lymphoma, and myeloma. Side effects from interferon are in general dissimilar to those that have been seen with pentostatin and in particular myelosuppression has not been a major toxicity with low doses of interferon. This current trial explored the combination of pentostatin and interferon in hematologic malignancies. Fifteen patients were enrolled in this phase I trial at a fixed dose of pentostatin of 4 mg/m2 biweekly and interferon at doses of 0.5, 1, 2, or 4 million units/m2 of interferon. At the first three dose levels of interferon nausea and vomiting were the predominant toxicity and appeared to worsen with time on study. Fatigue also was seen at the lowest level of interferon and was severe enough to cause two individuals to discontinue the study medications. At higher dose levels of interferon, myelosuppression, nausea and vomiting, and fatigue were the predominant toxicities. One patient with hairy cell leukemia had a complete response and a second patient with T cell cutaneous lymphoma had a partial response which lasted for 6 to 7 weeks. The maximum tolerated dose of interferon with pentostatin in this patient population was four million units/m2.
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PMID:A phase I trial of alpha-interferon in combination with pentostatin in hematologic malignancies. 205 72

Three patients with multiple myeloma were treated with recombinant alpha-interferon (r IFN-alpha 2b Intron AR) along with combination chemotherapy i.e. melphelan and prednisolone. In one case it was given as an initial therapy, while the other two patients had refractory and relapsing disease respectively. IFN-alpha 2b was given in the dose of 2 x 10(6) Mu/m2 by subcutaneous injection thrice in a week for six months in two patients and for three months in one patient. All three patients experienced improvement in bone pains; partial response with reduction in the paraprotein level was seen in one patient; while there was no radiological, biochemical or haematological improvement in two patients. Side effects noted were flu like syndrome in all three patients and urticaria in one patient. They were treated symptomatically and did not require cessation of interferon therapy.
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PMID:Recombinant alpha-interferon therapy in multiple myeloma. 209 May 74

Three patients with symptomatic multiple myeloma who had achieved an objective response after conventional induction chemotherapy were treated with alpha-2b-interferon plus intermittent high-dose dexamethasone as consolidation therapy. This treatment included three mega units of alpha-2b-interferon three times a week, plus 4 days pulsed high-dose dexamethasone every 28 days for 6 months. Toxicity was limited to a mild flu-like syndrome. A further and significant M-component reduction (50%), obtained after conventional chemotherapy, suggests the value of intermittent high-dose dexamethasone plus interferon as consolidation therapy.
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PMID:Consolidation treatment with dexamethasone and alpha-2B recombinant interferon further reduces the M-component level in multiple myeloma patients responding to conventional induction chemotherapy. 209 2

The use of interferon for the induction treatment of multiple myeloma has been shown to be effective in about 20 percent of patients. We studied its effects on long-term survival when it was used for maintenance treatment. Between April 1985 and May 1988, 101 patients with symptomatic multiple myeloma who had had a substantial objective response or a lesser objective response with disappearance of symptoms ("disease stabilization") after 12 courses of induction chemotherapy were randomly assigned to receive recombinant interferon alfa-2b as maintenance therapy (n = 50) or to receive no treatment (n = 51). As of December 1989, 66 of the 101 patients have relapsed (25 given interferon and 41 not treated). The median duration of response (from the time of randomization) was 26 months in the patients given interferon and 14 months in the untreated patients (P = 0.0002). A total of 37 patients have died (14 given interferon and 23 not treated). The median duration of survival (from randomization) was 52 months in the interferon group and 39 months in the control group (P = 0.0526). Among the patients who had had a substantial objective response to induction chemotherapy, the difference in survival time was statistically significant (P = 0.03526). Interferon had to be stopped because of toxic effects in 3 of 12 patients initially treated with 10 MU (megaunits) per square meter of body-surface area. After the dose was reduced to 3 MU per square meter, the only toxic effect was a mild influenza-like syndrome lasting two to three weeks. We conclude that maintenance treatment with interferon prolongs response and survival in patients with multiple myeloma who have responded to conventional induction chemotherapy.
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PMID:Maintenance treatment with recombinant interferon alfa-2b in patients with multiple myeloma responding to conventional induction chemotherapy. 218 56

Myeloma is a malignancy of plasma cells that are terminally differentiated B-lymphocytes. The clinical spectrum varies from the incidental discovery of a pathologically raised monoclonal immunoglobulin on routine electrophoresis in asymptomatic patients to widespread skeletal involvement with incapacitating bone pain. Symptoms may result from a solitary tumor mass, described as an extramedullary plasmacytoma, in virtually any part of the body. Metabolic abnormalities commonly include hypercalcemia, elevated plasma urate levels, or the development of amyloidosis, all of which may disturb renal function. High paraprotein levels cause hyperviscosity, resulting in generalized debility and varying degrees of disturbed mental function. The natural history is determined by the mass of the tumor coupled with its unique biologic features. Median survival of unselected patients, without effective treatment but once symptoms are evident, is approximately 7 months; this period can be significantly prolonged with appropriate therapy. As a first step, urgent medical management is often necessary, centering on rehydration, correction of hyperviscosity, and reversal of metabolic defects, each of which may improve renal function. Over the longer term, specific antitumor drugs have extended median survival to approximately 30 months, and most regimens include a combination of melphalan and prednisone, with or without other cytotoxic drugs. Alternative forms of treatment include sequential hemibody irradiation, recombinant alpha interferon, and in suitably selected patients, high-dose chemoradiotherapy followed by bone marrow transplantation. The latter approaches offer promising management options and are currently the subject of evaluation in controlled clinical trials.
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PMID:Myeloma. 218 18

The present pilot study was designed to analyse the efficacy and toxicity of the association of interferon (IFN) and dexamethasone (Dx) in 32 resistant and relapsed myeloma patients. Among the evaluable cases, 15 (68 per cent) responded to treatment (32 per cent achieved an objective response--OR--and 36 per cent a partial response--PR--), the 'remission' status lasting for more than one year in six of them. Moreover, four out of the seven OR patients showed a reduction in B.M. plasma cells to less than 5 per cent. Five out of 11 patients that were previously refractory to VBAD, that includes high dose dexamethasone (Dx), responded to IFN-Dx. The protocol was generally well tolerated with only four patients discontinuing therapy due to adverse effects. The present results show that the combination IFN + Dx is a promising therapeutic approach for patients with refractory myeloma.
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PMID:Combination of interferon and dexamethasone in refractory multiple myeloma. 221 Jun 87

During the past 5 years, several new treatments and strategies have been developed for patients with multiple myeloma. For patients with disease resistant to standard therapies, these include the VAD regimen, dexamethasone alone, high-dose melphalan, and intensive chemoradiotherapy with bone marrow transplantation. Alpha interferon appears to have its greatest potential as part of early induction therapy or during remission maintenance. The role of hemopoietic growth factors or blood stem cells in support of high-dose therapy and drugs that may overcome multiple drug resistance continues under study. A sequence of non-cross resistant therapies early in the disease course seems worthy of investigation, especially in patients at high risk for early relapse.
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PMID:New treatment strategies for multiple myeloma. 222 Jul 63

Alpha-2a-interferon (IFN) has demonstrable activity in advance and refractory multiple myeloma (MM), because of the in vitro synergism between IFNs and cytotoxic agents we report the preliminary results of a therapeutic trial of 50 patients with MM. Twenty-eight patients were randomized to receive melphalan plus prednisone (MP) and 22 were randomized to receive IFN plus MP (IFN-MP). Criteria for response, progression and relapse were those of the Southwestern Oncology Group. 95% of the patients receiving IFN-MP responded to therapy as opposed to 68% of the patients receiving MP (P less than 0.05). Response was independent of M-component immunoglobulin class but in stage III it was higher in the IFN-MP group than in the MP group (P less than 0.05). The combination IFN-MP was well tolerated without unusual or unexpected toxic effects. The response duration time was longer in the IFN-MP group than in the MP group (P less than 0.025). The median survival was 80 weeks in the MP group and in the IFN-MP group the 93% of patients were still alive after 90 weeks (P less than 0.025). Our results show that the use of the IFN as an adjuvant to MP improves the percentage of responders, the response duration time and the median survival of untreated patients with MM.
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PMID:Alpha-2a-interferon/melphalan/prednisone versus melphalan/prednisone in previously untreated patients with multiple myeloma. 226 47

The influence of interferon-induced fever on oral melphalan pharmacokinetics has been studied in 10 myeloma patients in a randomized crossover design. The melphalan dose (0.25 mg/kg) was given alone and 5 hours after the administration of human interferon alpha (7 x 10(6) IU/m2), respectively. The plasma concentration of melphalan was determined by liquid chromatography with fluorometric detection after derivatization of melphalan with N-acetylcysteine. The area under the plasma concentration-time curve (AUC) was significantly lower (p = 0.02) when melphalan was given with interferon. There was a significant negative correlation (p = 0.008) between body temperature and dose normalized AUC, whereas no effect was noticed on the maximum plasma concentration (Cmax) and on the time to obtain Cmax. The rate of elimination showed a tendency (p = 0.06) to increase with increasing body temperature. It is suggested that the cytotoxicity of the drug is most probably enhanced because of the higher alkylating activity of the compound at elevated body temperatures.
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PMID:Oral melphalan pharmacokinetics: influence of interferon-induced fever. 229 23


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