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)

Patients with Philadelphia chromosome-positive chronic myelogenous leukemia (CML) were treated with a combination of alpha-interferon and gamma-interferon. Recombinant alpha-2a-interferon (Roferon-A, Hoffmann-LaRoche, Inc., Nutley, NJ) and recombinant gamma-interferon (Genentech, Inc., South San Francisco, CA) were administered on alternating weeks each at doses ranging from 2 to 10 MU/m2 given intramuscularly. Of the 27 patients, 11 (41%) achieved complete hematologic remission (CHR) and 3 (11%) achieved partial hematologic remission (PHR). Responses were seen among 9 of 22 (41%) patients treated during the chronic phase of the disease and in 2 of 5 (40%) patients treated during the accelerated phase/second chronic phase. Cytogenetic responses were seen in six patients, including one complete response and five minor responses. Toxicities included flu-like symptoms, which appeared to be more severe with gamma-interferon than with alpha-interferon, hypertriglyceridemia, and thrombocytopenia. In this limited study, an improved outcome was not observed for the combination regimen compared with alpha-interferon alone.
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PMID:A phase II study alternating alpha-2a-interferon and gamma-interferon therapy in patients with chronic myelogenous leukemia. 191 50

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

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

A 35-year-old man died suddenly in a clinic waiting area after repeated visits for flu-like symptoms. At autopsy, hemoperitoneum, splenic capsular rupture, and splenomegaly were found. Microscopic examination, special stains, and immunoperoxidase studies revealed findings consistent with chronic myelogenous leukemia. Spontaneous splenic rupture is an unusual presenting feature of chronic myelogenous leukemia. The symptoms of leukemia may mimic those of other "benign" disorders and misdiagnosis may lead to catastrophic consequences in some instances.
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PMID:Splenic rupture as a cause of sudden death in undiagnosed chronic myelogenous leukemia. 317 55

Interferon-alpha 2b (IFN-alpha) was administered by continuous subcutaneous (s.c.) infusion to 23 patients with hematologic malignancies or metastatic solid tumors: 5 patients with multiple myeloma, 3 with malignant melanoma, 2 with chronic myelogenous leukemia (CML), 10 patients with renal cell cancer, and 3 patients with other solid tumors. Drug was delivered by continuous s.c. infusion for 28 days (1 cycle) at daily dose levels of 0.7, 1.4, 2.5, 3.6, or 5.0 X 10(6) IU/m2 to 3, 3, 3, 8, and 6 patients, respectively. At the highest dose level, a severe flu-like syndrome was seen in 3 patients and severe gastrointestinal toxicity in 2 patients. The maximally tolerated dose (MTD) was 3.6 X 10(6) IU/m2.day and the principal toxicity was a mild to moderate flu-like syndrome. Local skin reactions were occasionally noted at all dose levels if the s.c. needle site was not rotated every 3-4 days. At dose levels of 2.5-3.6 X 10(6) IU/m2.day, IFN-alpha serum levels at steady state ranged from 19 to 61 IU/ml. The time to achieve steady-state conditions ranged from 40 to 72 h and at steady state, 24 h area under the concentration time curve (AUC24 h) ranged from 480 to 1,464 IU/ml.h. Objective responses were seen 3 of 17 evaluable patients: 1/7 in renal cell cancer (14%); 1/2 in CML and in one patient with ependymoma. Remissions lasted 4, 8, and 15 months in renal cell, CML, and ependymoma, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase I-II trial of interferon-alpha 2b by continuous subcutaneous infusion over 28 days. 323 Mar 30

Alpha-2 interferon, produced in Escherichia coli using recombinant DNA techniques, was administered to 17 children with refractory acute lymphoblastic leukemia (ALL) in relapse, two children with TdT-positive, Philadelphia chromosome-positive chronic myelocytic leukemia (CML) in blast crisis, and one child with B cell (SIg+) non-Hodgkin's lymphoma (NHL) in a second extramedullary relapse. An initial 2-week intravenous (IV) phase of interferon was followed by a 3-month subcutaneous (SC) maintenance phase if patients had an objective response or disease stabilization without significant bleeding or infectious complications. When interferon dosages were escalated from 3 to 100 X 10(6) U/m2 in the first phase of therapy, there was rapid progression of disease in the first four patients treated, prompting a modification of the treatment plan. The last 16 patients enrolled received fixed dosages of interferon (ie, 10, 20, 30, and 50 X 10(6) U/m2 administered to four subjects each). One child with T cell ALL had an 11-month complete remission; the patient with lymphoma had a dramatic but brief response; three others (one CML and two ALL) showed disease stabilization for 3 to 6 months with a definite oncolytic effect in two of the three patients. The remaining 15 patients had progressive disease within 2 months and were removed from the study. Acute toxicity included a flu-like syndrome in all patients, increased serum transaminase levels in five, seizures in three (two cases temporally related to fever and one to a thrombocytopenic subarachnoid hemorrhage), and prolonged activated partial thromboplastin times in seven. This phase I-II trial of recombinant alpha-2 interferon demonstrated definite activity without dose-limiting toxicity.
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PMID:Phase I-II study of recombinant alpha-2 interferon against advanced leukemia and lymphoma in children. 345 76

From July 1983 to January 1991 a total of 622 patients were randomized (585 eligible) to compare the effects of hydroxyurea, interferon alpha (IFN), and busulfan on the duration of chronic phase, and survival. Further goals included the determination of prognostic parameters. 598 CML patients were documented and 575 evaluable. The Ph-status was known for 547 patients. 89.4% of the patients were Ph-positive (+). 11% had additional chromosome aberrations. The median survival of Ph+ patients by now is 4.2 years, that of Ph-patients 1.4 years. Ph-negative patients are older, tend to have lower cell counts and, as a group are more ill at diagnosis. A survival difference of about one year is expected between busulfan and hydroxyurea treated patients. Prospectively evaluated age, organomegaly related symptoms, Karnofsky index, extramedullary manifestations, number of erythroblasts and percent of circulating blasts proved to be of prognostic significance. A prognostic score (score 1) was determined which was superior to Sokal's score in the study population. 164 patients were randomized to receive IFN. In 54 patients (33%) IFN had to be terminated because of adverse effects, therapy resistance or other reasons. Clinically relevant neutralizing antibodies were detected in 9 cases. Most frequent adverse events were flu-like symptoms in 74%, gastrointestinal symptoms in 52%, and neurologic-psychiatric symptoms in 30% of patients. Reduction of the Ph-chromosome was observed in 13% of evaluable patients (10 of 75). In 4 patients complete cytogenetic remissions were observed, in three of these ongoing. Cytogenetic responders have a survival advantage. Interferon treated Philadelphia-negative CML patients have no survival disadvantage. The study is expected to allow statements as to the advantages or disadvantages of the use of busulfan, hydroxyurea and IFN in the treatment of CML as well as to the reliability of prognostic markers.
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PMID:The German CML study, comparison of busulfan vs. hydroxyurea vs. interferon alpha and establishment of prognostic score 1. 825 90

Fifty-one patients with CML in chronic phase, less than two years after diagnosis, were included in one multicentric study aiming to assess the therapeutic value of interferon alpha 2a (IFN alpha 2a) in this setting. The therapeutic scheme was biphasic: The patients were first treated with hydroxyurea, and afterwards only received IFN alpha 2a, at a planned dose of 5MU/m2/day, s.c. Thirty-eight patients (81%) achieved an hematologic response, which was complete in 57% of the total group. The median time to response was of 42 days. In the last evaluation, a complete hematologic response was sustained in 21 patients (47%). Philadelphia suppression was obtained in 44% of the patients who achieved hematologic responses; major cytogenetic responses were obtained in 16% of the patients. The patients who obtained genetic responses were significantly younger and had a shorter interval from diagnosis to IFN than the patients who did not respond. At the moment of evaluation, 90% of the patients are alive, but the median follow-up of the series (217 days, range 21-1150) is too short to analyze any impact of IFN over survival. Six patients (12%) discontinued IFN because of toxicity, three of them because of severe flu-like syndrome. Leukopenia and thrombocytopenia were frequent, but rarely severe. Hypertriglyceridemia has been a very frequent finding.
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PMID:Interferon alpha 2A in the treatment of chronic myelogenous leukemia in chronic phase. Results of the Spanish Group. 825 92

Adverse reactions to interferon-alpha (IFN-alpha) therapy include flu-like syndrome, bone marrow suppression, neurotoxic effects, and autoimmunity. A slight increase in triglyceride levels has been described less frequently during IFN-alpha administration. The incidence of IFN-alpha-induced hypertriglyceridemia seems variable, and there are no clear data on how to treat it. We report the effect of long-term (more than 12 months) IFN-alpha treatment on triglyceride levels in 43 patients suffering from hairy cell leukemia (18), multiple myeloma (10), chronic myelogenous leukemia (6), cryoglobulinemia (5), non-Hodgkin's lymphoma (3), and Sezary syndrome (1). Hypertriglyceridemia was found in 6 patients (15%). In 3 patients, gemfibrozil restored normal triglyceride values. This study suggests that hypertriglyceridemia is a minor side effect of long-term IFN-alpha therapy and that gemfibrozil might be considered the treatment of choice.
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PMID:Hypertriglyceridemia during long-term interferon-alpha therapy in a series of hematologic patients. 918 61

Mice with a null mutation of the gene encoding interferon consensus sequence-binding protein (ICSBP) develop a chronic myelogenous leukemia-like syndrome and mount impaired responses to certain viral and bacterial infections. To gain a mechanistic understanding of the contributions of ICSBP to humoral and cellular immunity, we characterized the responses of control and ICSBP-/- mice to infection with influenza A (flu) and Leishmania major (L. major). Mice of both genotypes survived infections with flu, but differed markedly in the isotype distribution of antiflu antibodies. In sera of normal mice, immunoglobulin (Ig)G2a antibodies were dominant over IgG1 antibodies, a pattern indicative of a T helper cell type 1 (Th1)-driven response. In sera of ICSBP-/- mice, however, IgG1 antibodies dominated over IgG2a antibodies, a pattern indicative of a Th2-driven response. The dominance of IgG1 and IgE over IgG2a was detected in the sera of uninfected mice as well. A seeming Th2 bias of ICSBP-deficient mice was also uncovered in their inability to control infection with L. major, where resistance is known to be dependent on IL-12 and IFN-gamma as components of a Th1 response. Infected ICSBP-deficient mice developed fulminant, disseminated leishmaniasis as a result of failure to mount a Th1-mediated curative response, although T cells remained capable of secreting IFN-gamma and macrophages of producing nitric oxide. Compromised Th1 differentiation in ICSBP-/- mice could not be attributed to hyporesponsiveness of CD4(+) T cells to interleukin (IL)-12; however, the ability of uninfected and infected ICSBP-deficient mice to produce IL-12 was markedly impaired. This indicates that ICSBP is a deciding factor in Th responses governing humoral and cellular immunity through its role in regulating IL-12 expression.
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PMID:Interferon (IFN) consensus sequence-binding protein, a transcription factor of the IFN regulatory factor family, regulates immune responses in vivo through control of interleukin 12 expression. 934 11


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