Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032463 (polycythemia vera)
 3,374 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interferon-alpha (IFN-alpha) exhibits a clear platelet reductive effect in patients with essential thrombocythemia as well as in other chronic myeloproliferative disorders with thrombocytosis. In a total of 51 patients with chronic myeloproliferative disorders with thrombocytosis we analyzed the effect of IFN-alpha in respect to platelet reduction, remission rates, induction- and maintenance dosage, long term tolerance and side effects. According to our classification CML 6, chronic mega-karyocytic granulocytic myelosis 5, essential thrombocythemia 26 and polycythemia vera 15 patients were treated. Treatment consisted of induction with 3 or 5 MU IFN-alpha daily followed by a maintenance therapy with 3 or 5 MU thrice weekly. Platelet reduction was found in all patients, CR (platelets < 450 G/l) in 78%. Within 2 months of induction therapy, CR in patients treated with 5 MU IFN daily was found in 75% compared to 52% in patients treated with 3 MU IFN daily. Dosage reduction in maintenance periode caused an increase of platelets to more than 450 G/l in 39% of patients. Out of 40 Philadelphia-negative chronic myeloproliferative disorders treated for more than 3 months in 10 patients treatment was disrupted after 5 to 18 months because of the following side effects: nausea, fatigue, vertigo, fever, headache, diarrhea, anorexia, heartburn, hairloss, myalgia, and thrombocytopenia. Due to the mutagenic effect of alkylating cytostatics and Radiophosphorus, IFN-alpha treatment represents a first line strategy for chronic myeloproliferative disorders with thrombocytosis especially in younger patients who are symptomatic and in those who suffered from episodes of bleeding or thrombosis.
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PMID:[Interferon therapy in essential thrombocythemia]. 827 65

The natural history of PRV is characterized by a prolonged period of myeloproliferation chiefly affecting the red cell series. It can be controlled by venesection and cytotoxic agents. In this case report the patient declined further 'standard' chemotherapy to control his disease and the use of relatively low doses of IFN-a was successful in our patient in controlling myeloproliferation and stabilizing the disease over a prolonged period. These results support the use of IFN-a, not only as a means of myelosuppression in PRV but also as an agent with the potential to prevent disease progression.
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PMID:Long-term control of polycythemia rubra vera with recombinant alpha interferon. 861 35

In previous researches recombinant interferon alpha (IFN-alpha) has been demonstrated to significantly control red cell mass and thrombocytemia in patients with polycythemia vera (PV). Further evaluation of drug effectiveness and of modalities of maintenance therapy is warranted. We treated four patients with PV according to PVSG criteria with IFN-alpha (3 MU subcutaneously three times a week) for five months. Thereafter the starting dose was reduced to 1.5 MU three times a week. Treatment with IFN-alpha at the higher dosage induced regression in sizes of the spleen and a return to normal levels of peripheral blood platelets and leukocytes. Phlebotomies, previously performed to keep under control hematocrit values, were no more needed. During maintenance treatment with IFN-alpha reduced dose platelet level remained in the normal range, spleen size did not show further variation but hematocrit slowly rose and phlebotomies had to be resumed. These results confirm IFN-alpha effectiveness in PV, but suggest the need of relatively high dosages of the drug and difficulties in switching to a maintenance treatment.
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PMID:[Alpha interferon in the therapy of polycythemia vera]. 871 Dec 55

Myeloproliferative disorders (MPD) are characterized by several common clinical and biological features, although at the molecular level, each disease entity exhibits distinct abnormalities. IFN-alpha exerts beneficial therapeutic effects in chronic myelogenous leukemia, polycythemia vera and essential thrombocythemia, resulting in control of hematopoietic hyperplasia and, in a minority of patients, in induction of cytogenetic remission. The mechanism of action of IFN-alpha in MPD is poorly defined. Recently published in vitro findings suggest that IFN-alpha interacts with the regulation of hematopoiesis by multiple ways. Its antiproliferative activity is well known for more than a decade, however, substantial growth inhibition is achieved only at relatively high concentrations. Defective adhesion of hematopoietic progenitor cells in CML to bone marrow stromal cells is corrected by IFN-alpha, which might expose CML progenitors to inhibitory cytokines produced by the bone marrow microenvironment. Recent work from our group demonstrated, that IFN-alpha potently interacts with the production of hematopoietic cytokines in bone marrow stromal cells. Expression of stimulatory cytokines, such as GM-CSF, G-CSF, IL-1 and IL-11 is inhibited by IFN-ct, whereas the production of negative regulators, such as IL-1RA and MIP-1 alpha, is stimulated. The combined action of IFN-alpha on paracrine expression of cytokines suggests an indirect antihematopoietic effect, which might contribute to its clinical activity in MPD.
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PMID:Influence of interferon-alpha on cytokine expression by the bone marrow microenvironment--impact on treatment of myeloproliferative disorders. 895 83

Aim of this study was to evaluate through an audit tool the appropriateness of interferon-alpha (IFN-alpha) prescribing in a teaching hospital. The records of all patients (n.665) treated with IFN-alpha since 1991 were reviewed and the data concerning diagnosis and treatment collected using a standardized from. The data were submitted for peer review to a panel which included the representatives of the different medical specialties which actually prescribed the drug, external experts and members of the health management board of the hospital. The following points were discussed:-adherence to accepted therapeutic indications:-accuracy of the diagnosis prior to treatment:-scheduled doses:-criteria defining non-responders;-length of treatment and criteria for discontinuation. At the end of the study a questionnaire for evaluation of the audit was submitted to all participants. Most patients were treated according to a diagnosis of chronic hepatitis (HCV, n.448; HBV, n.54; HDV, n.22); other indications were chronic myeloid leukemia, thrombocythemia, polycythemia vera, Kaposi's sarcoma, condylomata, melanoma and mycosis fungoides. All indications were approved by the panel: no patient was treated outside established indications (85.6%) or a clinical trial protocol (14.4%). Standard schedules were initially applied to each indication, and were adjusted if needed according to the clinical response. In conclusion, the audit showed that IFN-alpha was correctly prescribed in our teaching hospital; the procedure was well accepted and its application may be useful in modifying prescribing attitudes.
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PMID:[Application of clinical audit to the evaluation of prescription of interferon-alpha in a teaching hospital]. 899 9

In this study we firstly established a vaccination/challenge model to study pseudorabies virus infection in mice. The mouse model was used to investigate the significance of CD4+ and CD8+ cells and of IFN gamma production in protective immunity. Functional depletion of CD4+ and CD8+ and IFN gamma was obtained in vivo by intraperitoneal injection of alginate-encapsulated anti-CD4, -CD8 or -IFN gamma producing hybridoma's before and at the moment of vaccination. The observed protective immunity was correlated with underlying immunologic responses such as PRV-specific DTH reactivity, lymphoproliferation and cytotoxicity. The significance of CD4+ and CD8+ cells and of IFN gamma production was also investigated for these immunological responses by the same in vivo depletion technique. The results demonstrated that protective vaccination of mice, that could be induced by immunization with 10(7) plaque forming units of the avirulent PRV mutant NIA3 TK-, was characterized by a typical anti-viral Th1 type immune response. A clear PRV-specific, CD4-dependent DTH reactivity and a classical CD8-dependent, MHC-restricted cytotoxicity was induced after protective immunization and the humoral immune response had a bias towards PRV-specific IgG2a formation. In vivo treatment with anti-CD8 and anti-IFN gamma demonstrated that the cytotoxic response and humoral IgG2a response, respectively, were strongly reduced, whereas protection against lethal challenge was unaffected. On the other hand anti-CD4 treatment reduced the induced protection so that 30% of the mice died after lethal challenge. The results of our study demonstrated that CD4+, DTH like effector cells are a crucial effector mechanism for protective immunity against PRV.
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PMID:A mouse model to study immunity against pseudorabies virus infection: significance of CD4+ and CD8+ cells in protective immunity. 971 3

DNA vaccines have the capacity to induce strong Th1-biased immune responses that are of major importance to providing protection against intracellular pathogens. In the present study we have focused on the role played by type I IFN in immune responses induced after DNA vaccination. Mice lacking the IFNAR1 chain of the type I IFN receptor (IFNAR K/O mice) were immunized with a plasmid encoding glycoprotein C of pseudorabies virus (PRV-gC). After DNA vaccination, wild-type (WT) mice showed features characteristic of Th1 immune responses, such as high IgG2a:IgG1 anti-PRV Ab ratio and antigen-specific IFN-gamma production by spleen cells. In contrast, IFNAR K/O mice showed a significantly lower IgG2a:IgG1 Ab ratio and IFN-gamma production. In addition, the percentage of CD8(+) and B lymph-node cells expressing CD69 after PRV-gC DNA vaccination was lower in IFNAR K/O than in WT mice. These results support a major role played by type I IFN in shaping Th1 immune responses after DNA vaccination. Codelivery of plasmids encoding IL-12 and IL-18 along with the plasmid encoding PRV-gC restored Th1 responses in IFNAR K/O mice.
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PMID:Type I IFN modulates the immune response induced by DNA vaccination to pseudorabies virus glycoprotein C. 1144 72

Several options exist for treating essential thrombocythemia and polycythemia vera. One approach is to assign the patient to a risk category from which treatment recommendations follow. The principal risks of essential thrombocythemia include thrombosis, major hemorrhage, and conversion to leukemia or myelofibrosis. Risk factors for thrombosis include age and prior thrombosis. Smoking and obesity have been implicated in isolated series. High-risk patients with essential thrombocythemia can be defined as those 60 years of age or older or those who have had a thrombosis at any age. These patients should be treated with hydroxyurea. If hydroxyurea cannot be tolerated, anagrelide and interferon-alpha (IFN-alpha) are alternatives. Low-dose aspirin (40 to 325 mg) can be used for patients whose platelet counts are < 1,500 x10(9)/L. Low-risk patients are those less than 60 years old who have not had thrombosis, who have no cardiovascular risk factors, and whose platelet counts are < 1,500 x 10(9)/L. These patients can be observed or placed on low-dose aspirin. Intermediate-risk patients are those less than 60 years who have not had thromboses, but who have platelet counts > 1,500 x 10(9)/L or who have significant cardiovascular risk factors. These patients should have their risk factors treated and may be given low-dose aspirin if the platelet count is < 1,500 x 10(9)/L. They can be observed or treated with anagrelide, hydroxyurea, or IFN-alpha. The Mayo Clinic experience suggests that no specific treatment affects outcomes of pregnancies. In high-risk pregnant women who need treatment, IFN-alpha is used. The principal risks of polycythemia vera are thrombosis, postpolycythemia myeloid metaplasia, and acute leukemia. Risk factors for thrombosis include age, the use of phlebotomies, the rate of phlebotomies, and a prior history of thrombosis. Platelet counts have not been definitively linked to an increased risk of thrombosis. High-risk polycythemia vera patients are those 60 years of age or older (some groups use 70 years) or those of any age who have had thrombosis. They should be treated with phlebotomy and hydroxyurea or IFN-alpha. Selected patients may be treated with anagrelide. A typical target range for phlebotomy is a hematocrit of < 42% for women and < 45% for men. Low-dose aspirin can be used if the platelet count is < 1,500 x 10(9)/L. Low-risk patients are those less than 60 years old who have had no thrombosis, no cardiovascular risk factors, and whose platelets are < 1,500 x 10(9)/L. These patients can be managed with phlebotomy alone or phlebotomy and low-dose aspirin. Intermediate-risk patients are those who are less than 60 years old, who have not had thrombosis, but who have platelet counts > 1,500 x 10(9)/L or who have cardiovascular risk factors. The cardiovascular risk factors should be treated, along with phlebotomy alone or with IFN-alpha. Low-dose aspirin is reasonable for those with platelet counts < 1,500 x 10(9)/mL. Anagrelide can be used with phlebotomy in selected patients. Women of childbearing age who are in the low-risk or intermediate-risk group can be treated with phlebotomy alone and low-dose aspirin if the platelet count is < 1,500 x 10(9)/L. For high-risk patients or pregnant patients, IFN-alpha can be added.
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PMID:Therapeutic options for essential thrombocythemia and polycythemia vera. 1209 52

Polycythemia vera (PV), one of the chronic myeloproliferative disorders (MPD), is characterized by predominant erythroid proliferation and secondary platelet proliferation, and by progression from a proliferative stage to a metastatic phase and finally a malignant phase. These characteristics expose patients to increased risk for thrombohemorrhagic complications, myeloid metaplasia, myelofibrosis, and acute leukemic conversion irrespective of treatments. Currently, there are three agents-hydroxyurea (HU), interferon-alfa (IFN-alpha), and anagrelide-that differ in mechanisms of action and in treating specific phenotypic manifestations of PV, suggesting a potential role for combination therapy. They also differ widely in side effects profiles and severity. Because of the differing risks for long-term complications associated with these agents, age is an important variable in selecting treatments. Patients at high risk for thrombohemorrhagic complications all require cytoreduction, as do patients at intermediate risk who are not effectively managed by phlebotomy and low-dose aspirin. In younger patients, the safest and most effective combination treatment appears to be anagrelide plus IFN-alpha, while in older patients anagrelide plus hydroxyurea may be effective. HU is used sparingly in younger patients because of the long-term increased risk of mutagenicity and possibly leukemogenesis. IFN-alpha is particularly indicated for patients with myeloid metaplasia evidenced by splenomegaly. Anagrelide, which acts on the mature megakaryocyte to prevent platelet budding, is uniquely efficacious in the control of platelet counts.
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PMID:Modern treatment strategies in polycythemia vera. 1268 79

V617F JAK2 mutation is a reliable molecular marker of polycythemia vera (PV), potentially useful to monitor the effect of treatments in this disease. In a phase 2 study of pegylated (peg) IFN-alpha-2a in PV, we performed prospective sequential quantitative evaluation of the percentage of mutated JAK2 allele (%V617F) by real-time polymerase chain reaction (PCR). The %V617F decreased in 24 (89%) of 27 treated patients, from a mean of 49% to a mean of 27% (mean decrease of 44%; P < .001), and no evidence for a plateau was observed. In one patient, mutant JAK2 was no longer detectable after 12 months. In 3 patients homozygous for the mutation, reappearance of 50% of wild-type allele was observed during treatment. The results seem to confirm the hypothesis that IFN-alpha preferentially targets the malignant clone in PV and show that %V617F assessment using a quantitative method may provide the first tool to monitor minimal residual disease in PV. This trial was registered at www.clinicaltrials.gov as #NCT00241241.
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PMID:High molecular response rate of polycythemia vera patients treated with pegylated interferon alpha-2a. 1670 29


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