Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antiviral and antigrowth activity of interferon (IFN) makes this agent a promising approach to cancer therapy. Three tumors that are unusually sensitive to IFN-a are chronic myelogenous leukemia (CML) in the benign phase, hairy-cell leukemia, and the T-cell lymphomas associated with mycosis fungoides. Studies using partially purified IFN-a or IFN-A2a (Roferon-A) therapy have shown that most patients with benign-phase CML achieve hematologic remission. Furthermore, in some patients, long-term therapy results in hematologic remission and complete suppression of the Philadelphia chromosome. Early intervention, within six months after diagnosis, increases the response rate among CML patients treated with IFN-A2a. IFN-a, IFN-A2a (Roferon-A) and IFN-A2b (Intron A) are remarkably active against hairy-cell leukemia, with similar results achieved in clinical studies. The question of antibody formation in trials of recombinant IFN-a products will be discussed in this paper. Neutralizing antibody development and antibody positivity as determined by enzyme-linked immunosorbent assay (ELISA) have been reported with both IFN-A2a and IFN-A2b (Intron A), but the rate reported with IFN-A2b was significantly lower. However, possible differences in the sensitivity of the assays have been mentioned. The effects of differing dosing regimens also were noted. Additional trials conducted by clinical investigators using identical methods will help answer questions arising from these discrepancies and determine the full value of interferon in cancer therapy.
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PMID:The role of interferons in the treatment of hematologic malignancies. 245 80

Interferons are new and effective agents in the treatment of various haematological neoplasias. Alpha-interferon (natural or recombinant) has a high efficacy (90% response rate) in hairy cell leukaemia. Complete remissions are, however, rare and definite cure of the disease is unlikely. Alpha-interferon induces haematological remissions in about two thirds of patients with chronic myeloid leukaemia and leads to a reduction in Philadelphia chromosome in about 40% of patients. It is uncertain, however, whether this treatment will actually prolong the life of these patients as compared with conventional treatment. Alpha-interferon has a beneficial effect in some patients with low malignant non-Hodgkin lymphomas (in particular follicular lymphomas). The response rate in myeloma is rather small (20%). Gamma-interferon is not effective in hairy cell leukaemia, non-Hodgkin lymphoma and myeloma. It is, however, of some efficacy in chronic myeloid leukaemia (the response rate in lower than with alpha-interferon) and possibly has some effect in patients with acute myeloid leukaemia and myelodysplastic syndromes. The toxicity of interferons (alpha and gamma) consists of an influenza-like syndrome during the first days of treatment. Low doses of alpha-interferon show virtually no long-term toxicity. However, bone and muscular pain is sometimes dose-limiting with intermediate doses (5 to 15 million units) of alpha-interferon.
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PMID:[Interferon therapy in hematologic neoplasms]. 245 54

In the past decade, interferon, the first of a new class of biologic response modifiers, has undergone extensive Phase I and II clinical evaluation in a broad spectrum of cancers, including hematologic malignancies, lymphomas, and solid tumors. Interferon has been found to have important clinical activity in hairy-cell leukemia, low-grade non-Hodgkin's lymphoma, cutaneous T cell lymphoma, chronic myelogenous leukemia, previously untreated multiple myeloma, acquired immunodeficiency syndrome-related Kaposi's sarcoma, malignant carcinoid tumors, intravesically treated superficial bladder cancer, intraperitoneally treated ovarian carcinoma, renal cell carcinoma, and malignant melanoma. Recombinant DNA technology has produced molecules such as the interferons, which are antigenic and can induce antibody formation as part of a generalized immune response. The frequency of antibody occurrence, the magnitude of the antibody response, and the type of antibody induced by the interferons is thought to be related to several factors. These include the specific type of neoplasm for which interferon was administered; the specie of interferon administered; the dose, route, schedule, and duration of interferon administered; and the assay method and sampling time used to determine the antibody titer. Opinions and clinical observations about how these antibodies affect the clinical course of a disease vary among investigators. Some studies have demonstrated that antibody formation is associated with an abrogation of the clinical response, while others have not found any effects on the clinical course of a disease due to antibody presence.
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PMID:Biotherapy with interferon--1988. 246 49

Only the recent production of large amounts of highly purified recombinant interferons has made it possible to elucidate precisely the in vitro and in vivo effect of alpha- and gamma-interferon. Interferon-alpha has significantly widened the treatment modalities for some rare tumors such as hairy cell leukemia and chronic myelogenous leukemia. Although treatment results in solid tumors are disappointing, tumor regression greater than 50% is achieved in 15-25% of patients with hypernephroma or melanoma, cancers highly resistant to cytotoxic drugs. The solid tumors must be treated with high doses of interferon-alpha which causes severe side effects. Interferon-induced toxicity can be reduced by continuous subcutaneous infusion. Interferon-alpha is also used for the treatment of viral diseases such as chronic hepatitis-B, as well as for patients with AIDS and Kaposi sarcoma. Other virus infections such as herpes simplex and condylomata acuminata represent the few established indications for treatment with interferon-beta. Interferon-gamma has distinct immunomodulatory effects in vitro and in vivo, although the clinical significance of this potential has not yet been established. Thus far the treatment results in tumor patients have been poor. The future will show if the combination of interferons with other biological response modifiers, such as tumor necrosis factor or interleukin-2, or with cytotoxic drugs, brings further progress in cancer treatment.
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PMID:[Possibilities and limits of the use of interferons in the clinic]. 247 77

The effects and toxicities of interferon alfa are described, and the role of the pharmacist in making decisions and providing education about biologic response modifiers (BRMs) is discussed. Interferons have both direct antitumor activity and extensive effects on the immune system. Two recombinant interferon alfa products--interferon alfa-2a and interferon alfa-2b are available commercially. Indications in FDA-approved labeling for interferon alfa include the treatment of hairy-cell leukemia, acquired immunodeficiency syndrome-related Kaposi's sarcoma, and genital warts; however, it also is being used successfully against early chronic myelogenous leukemia, low-grade non-Hodgkin's lymphoma, cutaneous T-cell lymphoma, and previously untreated multiple myeloma. Other malignancies that respond to treatment with interferon alfa are malignant melanoma, ovarian carcinoma, and renal cell carcinoma. The toxic pattern of interferon alfa consists of flu-like symptoms, which are seen at all doses, on all schedules, and in virtually all patients. After repeated dosing, the chronic toxicities of anorexia, weight loss, and malaise and fatigue may develop. Myelosuppression, central nervous system toxicity, increased hepatic enzyme concentrations, nausea and vomiting, and cardiovascular toxicity also are possible. Serum neutralizing antibodies may be formed during therapy; this phenomenon may affect the clinical outcome. Numerous BRMs are being investigated for clinical use, and pharmacists must become conversant in the issues that surround these agents. Areas in which pharmacist involvement and knowledge are important include overall cost, product similarities and differences, dosing and scheduling, drug delivery systems, ways to minimize waste, adverse effects and their management, drug interactions, storage requirements, differences in production and purification techniques among manufacturers, and education of patients and staff.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biologic response modifiers: the interferon alfa experience. 248 96

Tumor necrosis factor alpha (TNF-alpha) and gamma-interferon (IFN-gamma) have been shown to suppress clonogenic growth in cultures containing blast cells obtained from patients with acute myeloid leukemia. We report that recombinant human TNF-alpha and IFN-gamma are also able to induce functional and morphological maturation in fresh myeloid leukemic cells in vitro. Assessing suspension cultures containing cells from patients with acute myeloid leukemia (11 patients) or myeloid blast crisis of chronic myeloid leukemia (5 patients), it was found that recombinant human TNF-alpha and IFN-gamma significantly enhanced the number of cells reducing nitroblue tetrazolium, as compared to control cultures containing no cytokine (P less than 0.001 and P less than 0.001, respectively). Cells from responders showed alterations characteristic of monocyte/macrophage differentiation, adherence to plastic surfaces, development of positive staining for alpha-naphthyl acetate esterase, typical morphology, and expression of cell surface antigens detected by the monoclonal antibodies Mo-1, Mo-2, and My-4. Both cytokines decreased the number of viable cells, the number of blast cells, and the number of cluster-forming units in suspension culture, suggesting inhibitory actions on the growth capacity of leukemic cells. Compared to the maximum effects of either factor alone, the combination of recombinant human TNF-alpha and IFN-gamma significantly increased the extent of growth inhibition and cell adherence but did not result in further increases in nitroblue tetrazolium reduction. The presence of Auer rods in IFN-gamma or TNF-alpha differentiation-induced macrophages with cells from a patient with M5 acute myeloid leukemia demonstrates that these cytokines can induce differentiation of a leukemic clone in primary cells from patients with leukemia.
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PMID:Differentiation-inducing effect of recombinant human tumor necrosis factor alpha and gamma-interferon in vitro on blast cells from patients with acute myeloid leukemia and myeloid blast crisis of chronic myeloid leukemia. 249 71

The clinical, hematologic and cytogenetic effects of human recombinant gamma interferon (IFN) were investigated in 14 patients with Ph+ chronic myeloid leukemia (CML). Gamma-IFN was given at a daily dosage of 0.50 mg (= 10 x 10(6) U)/m2 from the 3rd week of treatment on, but the dosage had to be reduced to 0.25 mg/m2 in 10 cases and to 0.35 mg/m2 in 2 cases, because of the severity and persistence of side effects (mainly fever, fatigue, headache and pain). Only 2 patients tolerated the full dosage. The overall response rate was 64% (1 complete and 8 partial hematologic responses). Only patients in stable chronic phase responded. Two out of two patients in unstable chronic phase and two out of two patients in accelerated phase failed to respond. Eight out of nine responding patients remained in remission throughout the duration of treatment (30 to 35 weeks). No karyotypic conversion was detected. These data show that gamma IFN alone is effective in Ph+ CML, but that side effects can limit substantially the dosage and duration of treatment.
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PMID:Treatment of Ph+ chronic myeloid leukemia by gamma interferon. 250 10

In 23 cases of chronic myelogenous leukemia (CML) in remission, HLA class II typing was performed by complement fixation technique on phytohemagglutin (PHA) activated lymphocytes. In 10 cases satisfactory results were obtained, whereas in 13 cases the cells were weakly or non reactive, making impossible a correct determination of HLA-DR,DQ specificities. In the 13 cases a conditioned medium containing Interleukin-2 (Il-2) and gamma interferon (IFN) was added to PHA, inducing a good HLA class II reactivity and making possible a satisfactory definition of HLA-DR,DQ specificities. The complement fixation technique on lymphocytes cultured with PHA, Il-2 and gamma IFN made possible a correct HLA-DR,DQ typing in 23 consecutive cases of CML, while such a typing is often difficult or impossible when using the microlymphocytotoxicity technique on B lymphocyte targets.
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PMID:[HLA class II typing in chronic myeloid leukemia with the complement fixation test using phytohemagglutinin-activated lymphocytes in the presence of interleukin 2 and gamma interferon]. 250 72

The effects of recombinant human interferon (IFN) alpha-2b and gamma on the bone marrow megakaryocyte progenitors (CFU-Meg) were compared between eight patients in the chronic phase of Ph1-positive chronic myelocytic leukemia (CML) and five hematologically normal patients. CFU-Meg was assayed in plasma clot culture added with phytohemagglutinin-stimulated leukocyte-conditioned medium as a source of colony stimulating activity. The average count of CFU-Meg colonies formed from the bone marrow of CML patients was 5.5 times that of normal controls. Spontaneous CFU-Meg colonies were grown in seven of eight CML patients, but in none of five controls. Colony formation by CFU-Meg in CML as well as normal bone marrow was suppressed by the two preparations of IFN in a dose dependent fashion. Their suppressive influence on colonies from CFU-Meg was comparable between CML and normal bone marrow at lower concentrations, but was less marked for CML than normal bone marrow at higher concentrations. The formation of CFU-Meg colonies from CML bone marrow was more severely suppressed by IFN-gamma than IFN-alpha-2b. Depletion of either T lymphocytes or adherent cells from the CML bone marrow cells diminished the suppressive effects of IFN-gamma, but had no influence on the effects of IFN-alpha-2b.
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PMID:[Effects of recombinant human alpha-2b and gamma interferons on bone marrow megakaryocyte progenitors (CFU-Meg) from patients with chronic myelocytic leukemia]. 251 97

Natural and recombinant interferons (IFNs) have already demonstrated therapeutic efficacy, including cytogenetic remissions, in patients with chronic myelocytic leukemia (CML). We investigated at the level of ligand-receptor interaction the question whether heterogeneity of receptor number or affinity might contribute to primary or secondary treatment failures in CML. We therefore analyzed IFN-gamma and IFN-alpha receptor expression and regulation during treatment with recombinant IFN-gamma and IFN-alpha in 15 patients with advanced CML. We found no difference in number or affinity of constitutively expressed IFN-gamma receptors (mean 1,100) and, on average, a 30% reduction of IFN-alpha receptors (mean 750) on peripheral blood mononuclear cells (PBMNC) of patients with chronic or accelerated CML as compared to mature granulocytes and/or bone marrow cells of healthy controls, which express on average 1,050 and 1,100 IFN-gamma and IFN-alpha receptors, respectively. While IFN-gamma receptor expression on PBMNC is not influenced upon treatment with rIFN-gamma, there is a substantial downregulation of IFN-alpha receptors in the course of rIFN-alpha therapy. Our data also show a differential pattern of receptor downregulation between patients achieving complete hematologic remission (CHR) (4 out of 12) compared with patients with partial hematologic remission (PHR) and non-responders. We conclude that differences in IFN receptor number cannot explain primary or secondary treatment failures. However, the differential ligand induced downregulation of IFN-alpha receptors in patients achieving CHR compared to those with PHR or non-responders suggest a prospective value of IFN-alpha receptor determination.
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PMID:Sequential therapy with recombinant interferons gamma and alpha in patients with unfavorable prognosis of chronic myelocytic leukemia: clinical responsiveness to recombinant IFN-alpha correlates with the degree of receptor down-regulation. 252 42


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