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

In 6 women aged 38 to 68 years with thrombocythaemia during chronic myeloid leukaemia (4 cases), myelofibrosis (1 case), and idiopathic thrombocythaemia (1 case) the effects of recombinant human alpha-interferon (Intron A, rh IFN alpha -2b, Schering) were studied. The drug was given to all patients subcutaneously in one daily dose of 3 x 10(6) u, every day for 3 weeks, and then in the same doses twice weekly for 2 weeks (5 cases) and for 14 weeks (1 case). Intron A caused in all cases a fall of peripheral blood platelet count by 37% to 65.5% (mean 50%) in relation to the initial count (532 - 1,453 x 10(9)/l). The fall of the platelet count occurred usually after 7-10 days of this treatment, and the lowest count was noted usually after 24 days (10 to 42 days). During the treatment in 4 cases the peripheral leucocyte count dropped as well by 20-70%. In no cases exacerbation of chronic myeloid leukaemia was noted, and in the patient with myelofibrosis the enlarged spleen shrunk somewhat. These results of treatment and follow-up of patients with thrombocythaemia treated with Intron A indicate a significant although short-lasting effect of platelet count fall limited, however, to the time of the treatment. Side effects of the drug included mainly febrile conditions, myalgia and arthralgia.
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PMID:[Effectiveness of interferon alfa in different stages of thrombocythemia (preliminary report)]. 182 71

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

Studies of the effect of interferon on the growth of colonies of myeloid leukemic blasts, myeloma colony-forming cells and normal hemopoietic precursor cells have shown that interferon does not specifically inhibit the growth of the malignant cells in culture, i.e. the growth of the malignant and the normal precursor cells are inhibited equally. However, interferon markedly reduces the self-renewal capacity of acute myeloid leukemic blasts and myeloma cells. This observation suggested that interferon should be tested for its ability to prolong remissions rather than as a remission-inducing agent. We have tested the ability of interferon alfa-2b (Intron A; Schering-Plough) to prolong remissions induced by busulfan in patients with chronic granulocytic leukemia (CGL). The leukocyte doubling time (Td) and remission duration on no therapy was compared to the values observed during interferon alfa-2b maintenance therapy. Fourteen patients have been started on study and seven have received interferon alfa-2b for three months or more. All seven have shown slowing of the leukocyte Td and prolongation of the remission duration after interferon alfa-2b therapy. A larger study, with longer follow-up, will be required to determine whether interferon alfa-2b therapy will slow or prevent progression of CGL to the blast phase and prolong survival.
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PMID:Interferon alfa-2b in the treatment of chronic granulocytic leukemia. 329 36

8 patients with chronic myeloid leukaemia in the chronic phase who had previously received chemotherapy were given alpha-interferon (Intron A). The Intron A was administered subcutaneously at a dose of 2 x 10(6) I.U./m2 three times a week and this was increased to 4-5 million I.U./m2 daily if no response was obtained after 6-8 months. 1 patient was Philadelphia chromosome-negative and was the only one who showed a major response to treatment. The other 7 patients never achieved haematologic remissions, or even a significant reduction in the immature blood leucocyte count or spleen size.
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PMID:Refractoriness to alpha-interferon (Intron A) in previously chemotherapy-treated patients with chronic myelocytic leukaemia. 336 20

Studies of the effect of interferon on the growth of colonies of myeloid leukemic blast cells, myeloma colony-forming cells, and normal hemopoietic precursor cells have demonstrated that interferon shows no specificity in inhibiting the growth of these cells in culture (ie, growth of the malignant and normal precursor cells is equally inhibited). However, interferon markedly reduces the self-renewal capacity of acute myeloid leukemic blast cells and myeloma cells. This observation suggested that interferon's ability to prolong rather than induce remissions should be tested. We have studied the ability of interferon alfa-2b (Intron A) to prolong remissions induced by busulfan (Myleran) in patients with chronic granulocytic leukemia (CGL). The leukocyte doubling time and remission duration among patients receiving no therapy was compared with the values observed during interferon alfa-2b maintenance therapy. Nine patients have begun the study; five have completed 3 months of interferon alfa-2b therapy. In four (80%) of the five patients, there has been a significant slowing of the leukocyte doubling time and prolongation of the remission duration. A larger study, with longer follow-up, will be required to determine whether interferon alfa-2b therapy will slow progression of CGL to the blast phase and prolong survival.
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PMID:Interferon alfa-2b in the treatment of chronic granulocytic leukemia. 346 99

Thirty-six patients with Philadelphia chromosome-positive CML were treated with interferon alfa-2b for at least 3 months. Thirty-two of the patients had chronic phase disease and four had acute phase disease, one in blast crisis. Patients initially received a daily dose of 4 megaunits/m2 administered subcutaneously; outpatient self administration followed at a dosage decreased in accordance with serially determined blood cell counts. Treatment was continued for 0.5 to 15 months, with a median duration of 7 months. No complete remission was achieved, but hematologic remission occurred in 21 (58%) patients, with partial hematologic remission in an additional 12 (33%). All four patients with acute phase disease failed to respond. Adverse reactions were only significant during the first days of treatment and did not interfere with self administration of the drug. Interferon alfa-2b may prove to be an important alternative therapeutic modality in chronic phase CML.
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PMID:Interferon alfa-2b in the treatment of chronic myelogenous leukemia. 347 89

Interferon alfa-2b (Intron A; Schering-Plough) was administered to 36 patients with chronic myeloid leukemia (CML) at an initial dose of 4 X 10(6) IU/m2 daily subcutaneously, adapted to changes in leukocyte counts during the course of treatment. Of 32 patients who could be fully evaluated (20 men and 12 women; median age, 34 years) 29 were in the chronic phase, one had a blast crisis and two had accelerated phase disease. Hematologic remission was achieved in 20 of the 32 patients, while a partial hematologic remission was obtained in 10. Elevated pretreatment white-cell counts returned to normal in 25 patients after 3-40 weeks. There was a parallel decrease in platelet counts after an average treatment time of six weeks and in lactate dehydrogenase, after 2-20 weeks. In conclusion, administration of interferon alfa-2b resulted in a relatively rapid cell reduction in chronic phase CML. The long-term effect of this treatment on the course of the disease and the place of interferon alfa-2b in the overall concept of CML treatment remains to be evaluated.
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PMID:Treatment of chronic myelogenous leukemia with recombinant interferon alfa-2b. 347 19

Chronic myelogenous leukemia (CML) involves the clonal expansion of hemopoietic progenitor cells associated with a characteristic translocation between chromosomes 9 and 22, resulting in the generation of an aberrant bcr-abl protein with enhanced tyrosine kinase activity. Although the precise molecular events leading to malignant expansion of the myeloid cell line are as yet undetermined, bcr-abl can induce cell proliferation, transformation of immature hemopoietic cells, and suppression of apoptosis in vitro. Abnormalities of stromal/progenitor cell interaction may be central to the pathogenesis of the abnormal hemopoiesis in CML. In chronic-phase CML, therapy with interferon-alfa (Intron A, Roferon-A) produces hematologic responses in up to 70% to 80% of patients and partial or complete cytogenetic responses in up to 50%, with many studies showing a significant overall survival advantage for responding patients. Allogeneic marrow transplantation can result in long-term survival and cure in patients with CML, particularly younger patients transplanted early in the course of the disease, and unrelated-donor or autologous marrow transplantation may be an option for patients without a matched sibling donor. Future therapy will likely involve selection and ex vivo expansion of nonleukemic stem cells for reinfusion as part of a strategy for autologous marrow transplantation.
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PMID:Biology and treatment of chronic myelogenous leukemia. 930 19

Chronic myelogenous leukemia (CML) is a myeloproliferative disorder that follows a characteristic clinical course in which a chronic phase of variable duration precedes an accelerated, and ultimately blastic, phase, which is generally fatal. This disorder results from a clonal expansion of transformed hematopoietic progenitor cells and includes myeloid, monocytic, erythroid, megakaryocytic, and lymphoid lineages. At the molecular level, CML is characterized by the bcr-abl fusion gene, which results from the reciprocal translocation t(9;22)(q34;q11), creating the Philadelphia (Ph) chromosome. Chronic myelogenous leukemia was the first human disease for which a specific karyotype abnormality was demonstrated and could be linked to pathogenetic events of leukemogenesis. The outlook for patients with CML has changed dramatically over the last decade. The median survival time of patients has doubled to 5 to 7 years, with up to 50% of patients alive at 5 years. This development is due to refinements in allogeneic stem-cell transplantation and growing expertise in the use of interferon-alfa (Intron A, Roferon-A), a biological agent that has been shown to suppress the leukemic clone and to prolong survival in patients with CML. This review provides a concise update of the biology of CML, as well as current therapeutic options and management strategies.
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PMID:Chronic myelogenous leukemia: update on biology and treatment. 1007 68