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)

Interferon alpha (INF-alpha)--In systemic diseases, most indications for INF-alpha result from its effect on haematological or hepatological manifestations. The spectacular effect of INF-alpha in chronic myeloid leukemia has led to its use for the treatment of hypereosinophilia syndrome and systemic mastocytosis. Over the last 6 years, we have treated 7 patients with the hypereosinophilia syndrome who were resistant to corticotherapy and had markers of myeloproliferation. Although both hydroxyurea and INF-alpha can be effective alone, their combination led to a decrease in the eosinophilia count to 1,000/ml, a decrease which was long-lasting in most cases. INF-alpha is also used in histiocytosis X alone or in combination with retinoids or with etoposide and has been found effective in several observations. In carcinoid syndromes whether treated priorly or not with a 5-fluoro-uracil-streptozoticin combination, INF-alpha leads to an objective response in two-thirds of the patients. Several multicentric protocols are currently assessing the efficacity of INF-alpha in mixed cryoglobulinaemias. In most observations these cryoglobulinaemias are seen in patients with markers of hepatitis C (mainly HCV) and the early results are encouraging. Temporary improvement has been reported in discoid or subacute lupus in 8 out of 10 cases. Haemangiomas of the infant, when life-threatening and corticoresistant, may be a good indication for INF-alpha. Thus 20 newborns or infants (including 4 with Kasabach-Merrit syndrome) have been treated with good results in 18. Interferon gamma (INF-gamma).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Interferons. Interferons alpha and gamma: indications in systemic diseases]. 817 44

The relationship between acute myeloid leukemia (AML), acute lymphocytic leukemia, chronic myeloid leukemia (CML), and refractory anemia with excess of blasts (RAEB) and antibodies to human T-cell lymphotropic virus types I and II (HTLV-I and HTLV-II), and hepatitis B virus and hepatitis C virus (HCV) was investigated in a multicenter case-control study. There were 431 cases enrolled in the study at the time of diagnosis of hematological malignancies, and 862 controls ages 15 years or older were recruited in three hospitals. Antibodies to HTLV-I and HTLV-II, antibody to HCV, hepatitis B surface antigen, and antibody to hepatitis B core antigen were assayed. All cases and controls were negative for HTLV-1 antibodies; one case (1 of 431; 0.2%), and one control (1 of 862; 0.1%) were found positive for HTLV-II antibodies. A nonsignificant excess of risk for hepatitis B surface antigen was present among RAEB cases (odds ratio, 2.40; 95% confidence interval, 0.46--12) CML, (odds ratio, 2.70; 95% CI, 0.86--8.43), and between antibody of hepatitis B core antigen and AML (odds ratio, 1.40; 95% CI, 0.93-2.10). A weak, nonsignificant association was present between AML, acute lymphocytic leukemia, RAEB, and antibody to HCV. These preliminary results suggest a possible association (elevated odds ratios) between hepatitis B virus, AML, RAEB, and CML. However, because all confidence intervals overlapped the null value, these findings need to be confirmed in larger case-control studies.
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PMID:Hepatitis B and C viruses, human T-cell lymphotropic virus types I and II, and leukemias: a case-control study. The Italian Leukemia Study Group. 883 24

Transmission of hepatitis C virus (HCV) in the setting of allogeneic bone marrow transplantation can occur through an infected marrow donor. Prevention of transmission may reduce the risks of peritransplant complications. We describe a 43-year-old patient with chronic myelogenous leukemia whose HLA-identical donor was found to be HCV antibody positive and HCV RNA positive by polymerase chain reaction (PCR). The patient was HCV antibody negative and HCV RNA negative by PCR of the serum. For 6 months before bone marrow transplantation, the donor was treated with alpha-interferon at a standard dose. After 3 months, HCV RNA was no longer detectable by PCR. Interferon was discontinued 1 week before harvest. Bone marrow cellularity was normal. Engraftment was prompt. The recipient's serum remained negative for HCV RNA at 1, 3, 5, and 10 months after transplantation. Hepatitis C transmission from a viremic donor to an HCV-seronegative recipient may be preventable by treating the donor with alpha-interferon.
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PMID:Prevention of transmission of hepatitis C virus in bone marrow transplantation by treating the donor with alpha-interferon. 893 86

Three patients who developed symptomatic, autoimmune-mediated thyroid dysfunction during treatment with interferon-alpha (IFN-alpha) for chronic active hepatitis C with liver cirrhosis, age-related macular degeneration with foveal involvement, and chronic myelogenous leukemia, respectively, are described. The first two patients developed autoimmune hypothyroidism that required thyroxine replacement, and the third developed autoimmune thyroiditis with transient thyrotoxicosis. The clinical manifestations were protean, and required a high index of suspicion for diagnosis, the failure of which led to significant morbidity. A literature review revealed that the mean incidence of IFN-alpha induced thyroid dysfunction was 6%. Spontaneous resolution occurred in more than half with discontinuation of IFN-alpha treatment. Hypothyroidism was induced more frequently than hyperthyroidism. At least one positive thyroid autoantibody titer was found in 17% of patients receiving IFN-alpha. Risk factors for developing thyroid dysfunction with IFN-alpha treatment were female sex, underlying malignancy or hepatitis C, higher doses of IFN-alpha for longer durations, combination immunotherapy (especially with interleukin-2), and the presence of thyroid autoantibodies prior to or during treatment.
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PMID:Interferon-alpha induced thyroid dysfunction: three clinical presentations and a review of the literature. 945 33

Chronic myelogenous leukemia (CML), hepatitis C, and interferon alpha (IFNalpha) have all been associated with renal dysfunction. In this paper we present a patient with the diagnosis of nephrotic syndrome and a known history of hepatitis C who received IFNalpha therapy for newly diagnosed CML. The renal biopsy showed focal segmental glomerulosclerosis, which has only been previously reported in two cases of CML treated with IFNalpha. There have also been two cases of patients with hepatitis C associated with focal segmental glomerulosclerosis. Despite the underlying hepatitis C, this case represents renal abnormalities consistent with IFNalpha therapy for CML.
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PMID:Interferon-alpha-induced focal segmental glomerulosclerosis in chronic myelogenous leukemia: a case report and review of the literature. 1279 97

Interferon (IFN)-alpha has demonstrated antitumor activity in a variety of solid and hematologic malignancies, including metastatic renal cell carcinoma. Pegylation, the process of combining a polyethylene glycol moiety to a biologic protein, substantially changes the pharmacokinetic profile of a drug, resulting in prolongation in half-life, increased area under the curve and, in some cases, improved efficacy. Pegylated IFN-alpha has been evaluated in chronic hepatitis C, chronic myelogenous leukemia and most recently in metastatic renal cell carcinoma. Registrational studies of pegylated IFN-alpha2a (PEGASYS) and pegylated IFN-alpha2b (PEG Intron) in patients with hepatitis C demonstrated greater efficacy with similar safety and tolerability to nonpegylated IFNs, with the advantage of less frequent administration. Studies evaluating these agents in the treatment of metastatic renal cell carcinoma and other cancers are ongoing.
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PMID:Evolving role of pegylated interferons in metastatic renal cell carcinoma. 1468 4

Pegylated interferon alfa-2b is a formulation of recombinant human interferon conjugated with polyethylene glycol. Compared with standard interferon alfa injections, this preparation has a longer half-life allowing for once-weekly injections and superior antiviral efficacy in the treatment of hepatitis C when used in combination with ribavirin. Cutaneous side effects caused by interferon are well known. Cutaneous necrosis as a result of interferon alfa is an infrequent complication with unknown pathogenesis, in which a cutaneous local immune-mediated inflammatory process might be involved. We report 5 patients (3 patients with chronic hepatitis C treated with pegylated interferon alfa-2b in association with oral ribavirin and two patients with chronic myelocytic leukemia) who developed local cutaneous reactions at sites of injection after the administration of weekly subcutaneous injections of pegylated interferon alfa-2b at different doses. The ulcers slowly healed with local therapy, but two patients required dose modification of the pegylated interferon alfa-2b and one patient required treatment withdrawal. We review the literature on previously reported cases of cutaneous necrosis after injection of standard interferon alfa or pegylated interferon alfa-2b and discuss the different pathophysiologic mechanisms that might be involved.
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PMID:Cutaneous necrosis after injection of polyethylene glycol-modified interferon alfa. 1596 22

Hepatitis C viral infection is a global health problem that affects approximately 4 million people in the United States. Combination treatment with pegylated interferon (IFN)-alpha plus ribavirin has been shown to be most effective in treating patients with chronic hepatitis C (CHC). Despite its efficacy, one of the most common side effects of this regimen is depression. Whereas IFN-alpha has been found to induce depression in chronic myelogenous leukemia, melanoma, and renal cell carcinoma, CHC patients may be especially prone to develop IFN-induced depression. This review includes a summary of differences between IFN-alpha and IFN-beta and addresses whether pegylation of IFN (versus nonpegylated IFN) gives rise to a treatment with reduced potential to induce depressive symptoms. Consideration is also given to evidence showing that treatment with ribavirin may contribute to IFN-induced depression. Thyroid disorders and anemia (as well as other medical conditions) have also been associated with IFN exposure and may account for some incidences of depression in CHC patients. Evidence is reviewed indicating that prior psychiatric and mood disorders (especially previous episodes of major depressive disorder), just prior to IFN treatment, contribute to the propensity to develop depression during treatment. In addition, a brief description is provided of potential biological mechanisms of IFN-induced depression (ie, monoamines, hypothalamic-pituitary-adrenocortical [HPA] axis, proinflammatory cytokines, peptidases, intercellular adhesion molecule-1, and nitric oxide). Finally, a discussion is provided on the use of antidepressants as a preventative versus restorative treatment, including a commentary on risks of using antidepressants in this patient population.
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PMID:Interferon-induced depression in chronic hepatitis C: a review of its prevalence, risk factors, biology, and treatment approaches. 1741 17

After allogeneic hematopoietic stem cell transplantation (HSCT), early infections represent a major cause of morbidity and mortality but little information has been previously reported on late infections. Late infection incidence and risk factors were retrospectively determined in 196 long-term survivors after HLA matched related HSCT. Patients transplanted for aplastic anemia, chronic myelogenous leukemia (CML), and acute myelogenous leukemia (AML) were included. Median follow-up was 8 years. Thirty patients died beyond the first year, causes of death were relapse (n = 10) and infections (n = 19, associated with graft-versus-host disease [GVHD] in 16 patients). Late severe bacterial (LSB) and fungal infections occurred in 30 and 8 patients, yielding to an 8-year cumulative incidence of 15 (95%CI: 10-20) and 4% (95%CI: 1-6), respectively. The majority of viral infections were hepatitis C (HCV) and VZV (8-year cumulative incidence: 10 (95%CI: 5-14) and 27% (95%CI: 20-34), respectively. Three risk factors for LSB have been identified in multiple Cox analysis: CMV status (positive recipient and negative donor) (hazard ratio [HR]: 2.5, 95%CI: 1.1-5.9, P = .033), irradiation-based conditioning regimen (HR: 3.1, 95%CI: 1.2-7.8, P = .016), and extensive chronic GVHD (cGVHD; HR: 2.9, 95%CI: 1.3-6.9, P = .013). Extensive cGVHD was the only risk factor for non-HCV viral infections in patients transplanted for AML or CML (HR: 2.7, 95%CI: 1.4-5.1, P = .002). After HSCT, patients remain at high risk of infections even late after transplantation, in particular, with the above risk factors, and required a prolonged follow-up.
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PMID:Risk factors for late infections after allogeneic hematopoietic stem cell transplantation from a matched related donor. 1795 Sep 17

This note mechanistically accounts for recent unexplained findings that all-trans retinoic acid (ATRA, also termed tretinoin) exerts an anti-viral effect against hepatitis C virus (HCV) in chronically infected patients, in whom ATRA also showed synergy with interferon-alpha. How HCV replication was suppressed was unclear. Both effects of ATRA can be accounted for by ATRA's upregulation of RIG protein, an 18 kDa product of retinoic induced gene-1. Increased RIG then couples ATRA to increased Type 1 interferons' production. Details of this mechanism predict that ATRA will similarly augment interferon-a activity in treating chronic myelogenous leukemia, melanoma, myeloma and renal cell carcinoma and that the addition of ribavirin and/or bexarotene will each incrementally enhance interferon-a responses in these cancers.
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PMID:Potential for all-trans retinoic acid (tretinoin) to enhance interferon-alpha treatment response in chronic myelogenous leukemia, melanoma, myeloma and renal cell carcinoma. 1876 14


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