Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Before proceeding to treatment selection for multiple myeloma, it is important to exclude monoclonal gammopathy of unknown significance or any similar smouldering or indolent type of myeloma not requiring immediate chemotherapy. In patients with active myeloma, pretreatment prognostic classification is important for appropriate balancing of the risks and benefits of particular treatment options. For example, conventional chemotherapy such as melphalan/prednisone may be appropriate for an elderly patient with active stage III myeloma, whereas high dose chemotherapy with or without bone marrow transplantation or cytokine support may be considered for the patient under age 45 with even earlier stage disease. A variety of options are now available for patients with relapsing or resistant disease, particularly using agents with potential for reversal of multi-drug resistance. The use of interferon-alpha as maintenance following initial response to chemotherapy is important for prolongation of remission, duration and potentially survival. A variety of supportive measures are also helpful including the use of epoetin (erythropoietin) to improve refractory anaemia and bisphosphonates for the inhibition of ongoing bone resorption. With the availability of various treatment options, it has become important for patients to be evaluated by a specialist in the field.
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PMID:Multiple myeloma. New treatment options. 138 12

A total of 25 patients with metastatic renal cancer were treated on a phase II protocol with 5 days of continuous-infusion fluorodeoxyuridine (FUDR), (0.1 mg/kg daily) together with high-dose oral leucovorin (100 mg 4 h) and daily x6 high-dose interferon-alpha 2b (30 x 10(6) IU/m2). Despite the good performance status of the patients and the inclusion of 14 previously untreated patients in the cohort, no response was observed among the 20 evaluable patients. Toxicities included high fever, moderate anemia, transient leukopenia, transient and mild elevations of transaminases, and moderate to severe nausea, vomiting, diarrhea, and mucositis. There were also two episodes each of confusion, fluid retention, and pancreatitis and one episode of increased creatinine levels. During the study three deaths occurred, two of which were possibly therapy-related. Despite previous reports of activity of FUDR in metastatic renal cancer, the present regimen cannot be recommended.
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PMID:Continuous-infusion fluorodeoxyuridine with leucovorin and high-dose interferon: a phase II study in metastatic renal-cell cancer. 146 58

As a result of a pathophysiologically unexplainable bone marrow failure, most patients with progressive stages of human immunodeficiency virus (HIV) infection develop anemia, leukopenia, and thrombocytopenia. Besides the possibility of immune-mediated cytolysis or of direct viral infection of hemopoietic progenitor cells, the inhibitory influence of cytokines, for example interferon-alpha (IFN-alpha) and IFN-gamma, on hemopoiesis of HIV-infected patients might be considered as one parameter that contributes to myelosuppression. Therefore, progenitor cells from the bone marrow of HIV+ and HIV- persons were exposed to increasing concentrations of recombinant human IFN-alpha and IFN-gamma in methylcellulose assays. The colony formation of pluripotent (CFU-GEMM), erythroid (BFU-E), and granulocyte-macrophage (CFU-GM) progenitor cells was inhibited by both interferons. The 50% inhibitory doses (ID50) of IFN-alpha were 125.6 U/mL and 131.5 U/mL for BFU-E from HIV-infected persons and normal controls, respectively; the corresponding ID50 of IFN-alpha for CFU-GM growth was 1095.8 U/ml and above 3000 U/ml. When IFN-gamma was studied the ID50 was 341.7 and 2794.6 U/ml for BFU-E from HIV-infected and healthy individuals, respectively, while the ID50 for CFU-GM was above the highest dose levels in both groups (greater than 3000 U/ml). The ID50 for CFU-GEMM was below the lowest dose levels of IFN alpha and IFN gamma tested in both groups (less than 10 U/ml). The inhibitory effects could be specifically neutralized by monoclonal antibodies against IFN-alpha and IFN-gamma, thus confirming that the suppressive effects were due to the cytokines used.
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PMID:Influence of human recombinant interferon-alpha and interferon-gamma on bone marrow progenitor cells of HIV-positive individuals. 159 59

To determine the safety, maximum tolerated dose, and preliminary efficacy of concomitant interferon-alpha and zidovudine therapy in AIDS-related Kaposi's sarcoma (KS), 56 patients with biopsy-proven KS and documented human immunodeficiency virus type 1 (HIV) infection were enrolled into a phase I study. Interferon-alpha was given intramuscularly at a dose of 9, 18, or 27 mu once a day and zidovudine was administered as 100 or 200 mg every 4 h for 8 weeks followed by a 48-week maintenance period. The major toxicities were anemia, neutropenia, and hepatotoxicity. Neutropenia was dose limiting with 1,200 mg of zidovudine/day and the lowest dose of interferon-alpha (9 mu/day). Hepatotoxicity was dose limiting with 27 mu of interferon and 600 mg of zidovudine/day. Cumulative dose-related anemia or neutropenia was not seen during long-term follow-up. The maximum tolerated doses for the combination were defined as 18 mu daily for interferon-alpha and 600 mg daily for zidovudine. Variable changes in CD4 lymphocytes occurred during the first 8 weeks of therapy. At higher doses of the combination, sustained increases in median CD4 lymphocyte numbers were noted (p less than 0.001). In HIV antigenemic patients, progressive antigen suppression was seen with increasing doses of the combination (p less than 0.005). The overall antitumor response rate was 47%. Tumor regression was associated with better survival benefits (p less than 0.001) and a pretreatment CD4 cell count greater than or equal to 200 cells/mm3 (p = 0.01). In conclusion, intermediate doses of interferon-alpha and lower doses of zidovudine appear to be relatively well tolerated and associated with disease improvement, including survival benefits.
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PMID:A phase I study of recombinant human interferon-alpha 2a or human lymphoblastoid interferon-alpha n1 and concomitant zidovudine in patients with AIDS-related Kaposi's sarcoma. 167 May 85

Twenty-four patients infected with human immunodeficiency virus type 1 (HIV-1) who had CD4+ counts of 0.2-0.5 x 10(9) cells/l received granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination with zidovudine plus escalating doses of daily subcutaneous interferon-alpha. Mean neutropenia-inducing doses of interferon-alpha were 9.4 x 10(6) and 10.6 x 10(6) IU/day for groups receiving 100 or 200 mg zidovudine every 4 h, respectively. Mean GM-CSF doses used to reverse neutropenia were 0.64 and 0.63 microgram/kg/day for these two groups, respectively, although the mean minimum effective GM-CSF dose for both was only 0.30 microgram/kg/day. Serum p24 antigen declined greater than 70% in all 5 antigenemic patients. Toxicities included a dose-dependent increase in lymphokine-like side effects (100%), anorexia and weight loss (42%), fatigue (42%), and anemia (50%). While toxicities of the combination can be significant, low-dose GM-CSF readily ameliorated neutropenia associated with zidovudine and interferon-alpha therapy without adversely affecting the antiviral properties of the combination.
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PMID:A phase I/II trial of zidovudine, interferon-alpha, and granulocyte-macrophage colony-stimulating factor in the treatment of human immunodeficiency virus type 1 infection. 167 45

The recombinant cytokines are increasingly important therapeutic agents for patients with AIDS. Recombinant interferon-alpha has demonstrated antitumor and antiretroviral activities in patients with Kaposi's sarcoma. Limited studies with interferon-beta suggest that it also has antitumor effects in patients with Kaposi's sarcoma, but interferon-gamma appears to be ineffective in controlling this tumor. The hematopoietic growth factors, including erythropoietin, granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF), have been evaluated in several populations of human immunodeficiency virus (HIV)-infected individuals. The combination of G-CSF and recombinant human erythropoietin completely reversed the zidovudine-induced neutropenia of AIDS patients but was only partially effective in reversing anemia. In several clinical trials, GM-CSF induced marked increases in leukocyte counts and improved neutrophil function in some AIDS patients. In severely immunocompromised patients with disease caused by HIV who were receiving therapy with either G-CSF or GM-CSF, opportunistic infections continued to occur despite increases in circulating white blood cell counts. Recombinant cytokines may be used in the future in AIDS patients as adjunctive treatment with myelosuppressive antibiotics and chemotherapeutic drugs, as a possible means of enhancing host defense, or as agents of immune reconstitution.
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PMID:Use of recombinant interferons and hematopoietic growth factors in patients infected with human immunodeficiency virus. 196 13

A 60-year-old woman was admitted to our hospital because of gastric ulcer, anemia, and leukocytosis in November 1984. Blood cell counts on admission were as follows: RBC 407 x 10(4)/microliters, Hb 9.8 g/dl, WBC 33,000/microliters (baso 8%, eo 7%, myelo 11%, meta 2%, stab 4%, seg 54%), Plt 93.7 x 10(4)/microliters. Bone marrow showed hypercellular and myeloid hyperplasia. She was diagnosed as Ph1-chromosome positive chronic myelogenous leukemia. She received natural interferon-alpha at the dosage of 600 x 10(4) IU daily for 22 days from January 14, 1985. After March 1985, she has been given intermittent administration of interferon once in 10 to 20 days, and maintained normal blood cell counts. Cytogenetic improvement was seen on 35 months after the start of IFN and complete suppression of Ph1 chromosome was observed at July 1990 (66 months after).
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PMID:[Intermittent administration of natural interferon-alpha for over 5 years induced complete suppression of Philadelphia chromosome in a patient with myelogenous leukemia]. 177 60

A successful induction of remission in two patients with resistant multiple myeloma using a new combination therapy of modified M-2 protocol and interferon-alpha (IFN-alpha) is described. The first case was a 32-year-old man with K type urinary Bence-Jones protein who became resistant after treatment with melphalan and prednisone (MP protocol). IFN-alpha alone had a marginal response. The modified M-2 protocol proved insufficient. Therefore, IFN-alpha was administered in the interval of M-2 protocol. This combination therapy showed remarkable responses. The second case was a 59-year-old woman with advanced IgA myeloma who was treated with M-2 protocol and became resistant. IFN-alpha alone resulted in a slight response. After addition of IFN-alpha to the modified M-2 protocol, a rapid reduction in the level of serum IgA was found and clinical symptoms including bone pain, anaemia and so on were dramatically improved. No infection and/or intolerable side effects were observed in either case. This combination treatment appears worthy to try in cases of resistant or relapsing myeloma patients.
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PMID:Combination therapy of M2-protocol and interferon-alpha as remission induction in refractory multiple myeloma. 181 63

The antiretroviral activity, tolerance and toxicity of two different antiviral drug combinations were assessed and compared in a randomized, crossover pilot study in 16 HIV-1 p24 antigenaemic subjects with asymptomatic HIV infection. Oral zidovudine 250 mg twice daily was combined with either oral acyclovir 800 mg twice daily or lymphoblastoid interferon-alpha 1.5 x 10(6) IU administered subcutaneously three times weekly. The 12-week treatment period was followed by a 4-week washout period and a further 12-week crossover phase. During the entire treatment period a decline in p24 antigen was observed in all patients. No significant differences were found between the two treatment regimens. No patient showed clinical progression of HIV infection. Three patients were withdrawn from the study, one due to serious anaemia and two due to severe clinical adverse events. Long-term efficacy and tolerance data in asymptomatic HIV-infected patients with these regimens would be valuable.
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PMID:Low-dose zidovudine in combination with either acyclovir or lymphoblastoid interferon-alpha in asymptomatic HIV-infected patients: a pilot study. 181 9

A 69-year-old man with agnogenic myeloid metaplasia was treated with interferon-alpha 2 as part of a Phase II clinical trial. The patient responded to this treatment with a definite improvement in bone marrow histology, demonstrating increased numbers of hematopoietic colonies and partial resorption of the myelofibrosis. Chromosomal analysis on 20 cells suggested the re-emergence of normal hematopoietic progenitor cells: whereas previously, all metaphase spreads demonstrated a deletion in chromosome 20, the patient was now chimeric, with two of 20 cells exhibiting a normal karyotype. Nevertheless, the patient's anemia progressed during interferon therapy, with the development of an immunologically mediated hemolytic disorder. This hemolytic process developed after prolonged treatment with interferon, accelerated during therapy, and resolved following splenectomy and withdrawal of the drug. Initially, screening tests failed to detect the presence of the autoantibody. Similar immunologic processes may have been overlooked in other patients treated with interferon, especially if tests for autoantibodies were obtained early in their course of treatment. This case suggests a therapeutic role for interferon-alpha 2 in the management of the myeloproliferative diseases. It is presented, too, to underscore the immunomodulatory potential of the biologic response modifiers and their capacity to induce immunologic disorders.
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PMID:Interferon therapy for agnogenic myeloid metaplasia complicated by immune hemolytic anemia. 189 85


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