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)

The use of radioactive phosphorus (32P) to treat the myeloproliferative disorders (chronic leukemia, polycythemia vera and essential thrombocythemia) began in 1939 when John H. Lawrence treated the first patient on the basis of work done in the laboratory animals that found localization of the radioisotope in the spleen, liver, bone and in leukemic cells sufficient to indicate a therapeutic potential. After World War II when 32P became widely available, it was used extensively to treat the chronic leukemias and polycythemia vera. Its use in the treatment of essential thrombocythemia began later in 1950. Today it is not widely used in the treatment of the chronic leukemia, if at all, its use in polycythemia vera appears to have decreased substantially and replaced by hydroxyurea, and its use in the management of essential thrombocythemia is not widespread. In each instance it has been replaced by a drug developed for use in cancer chemotherapy, and in some instances by interferon. It probably has wider use in polycythemia vera in the rest of Western Europe than in the UK, and there are cogent reasons to suggest that it may be the best tool for the treatment of polycythemia vera. Thus have we discarded a treatment modality that in polycythemia vera may be the best?
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PMID:Treatment of the myeloproliferative disorders with 32P. 1091 33

Myeloproliferative diseases (MPD) include polycythemia vera (PV), essential thrombocythemia, agnogenic myeloid metaplasia, and chronic myelogenous leukemia. The focus of this report is on PV, which is characterized by an increase in red blood cells, granulocytes, and platelets. Complications associated with PV are an increased risk of thrombosis and abnormal bleeding. Phlebotomy to a hematocrit less than 45% is the mainstay of treatment for erythrocythemia, but may further increase the platelet count, necessitating the use of a platelet-lowering agent in conjunction with phlebotomy. Other treatment strategies include low-dose aspirin or other antithrombotic therapy and cytoreduction. Mounting evidence of the leukemogenicity and mutagenicity of radioactive phosphorus and alkylating agents, as administered using "conventional" regimens, has restricted the liberal use of these treatments. Three drugs have emerged as useful because of their efficacy in reducing the elevated platelet count: anagrelide, hydroxyurea (HU), and interferon alfa (IFN). It is clear that no single agent satisfies all the needs for cytoreduction that arise during the course of PV. Future protocols should be designed that draw on the large body of experience already gained with these drugs to transcend the limitations of single-agent therapy and to improve quality of life as well as survival. Semin Hematol 38(suppl 2):25-28.
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PMID:Current management in polycythemia vera. 1124 99

Polycythaemia vera (PV) and essential thrombocytosis (ET) are clinically characterised by non-specific neurologic symptoms, peripheral circulatory disturbances (acrocyanosis, wounds, erythromelalgia) or abdominal symptoms. The treatment of PV includes phlebotomy, antiaggregation and cytoreduction. In ET, the primary treatment is also low-dose aspirin except for patients presenting with a haemorrhagic diathesis. Hydroxyurea may be associated with an increased risk of acute leukaemia or myelodysplasia. Therefore alpha-interferon and anagrelide should be considered in younger patients. Early cytoreductive therapy is advocated in patients with idiopathic myelofibrosis (IMF) to inhibit further progression of bone marrow fibrosis and further expansion of myeloid metaplasia in the spleen and liver. Treatment with androgens (danazol) and glucocorticoids may improve severe anaemia and thrombocytopenia. In younger patients, allogeneic bone marrow transplantation should be considered.
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PMID:[The chronic Philadelphia chromosome-negative myeloproliferative syndrome II. Clinical findings, diagnostics and treatment]. 1137 60

Except for chronic myelogenous leukemia (CML), chronic myeloproliferative disorders (CMPDs) include as main subtypes polycythemia vera (PV), chronic idiopathic myelofibrosis (IMF), and essential thrombocythemia (ET). A common finding in CMPDs is a clonal evolution associated with a significantly variable course, which may be complicated by thrombocythemia, (secondary) myelofibrosis, and finally acceleration (unstable phase) that merges into blastic crisis. New therapeutic modalities (chemo- and interferon therapy, bone marrow and stem cell transplantation) which were developed in the last decade and the striking differences in survival amongst the different subtypes warrant not only an unequivocal distinction from reactive and allied disorders, but a clear-cut classification as well. For this reason, a synoptical approach is essential including clinical data and, as a major diagnostic tool, a bone marrow biopsy. This concept finds expression in the new WHO classification, which also includes as rare subtypes chronic neutrophilic leukemia, eosinophilic leukemia, chronic hypereosinophilic syndrome, and finally unclassifiable entities. Histopathology of bone marrow biopsies reveals specific findings, in particular concerning megakaryopoiesis, which are characteristic for the different subtypes. These features facilitate the still controversially discussed differentiation of thrombocythemia that is frequently present, as is the case in initial (prefibrotic) IMF from ET. Moreover, in addition to clinical findings,the associated heterogeneity of bone marrow morphology indicates a stepwise evolution of the disease process and thus exerts a significant impact on survival, i.e., in CML regarding erythropoiesis and myelofibrosis and in IMF extent of myeloid metaplasia.
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PMID:[Chronic myeloproliferative disorders. The new WHO classification]. 1176 43

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

Myelofibrosis with myeloid metaplasia, also known as idiopathic myelofibrosis (IF) or agnogenic myeloid metaplasia, is one of the characteristic manifestations of polycythemia vera (PV) in the spent phase, and has a particularly adverse prognosis. IF may also present de novo. To date, treatment strategies for both spent-phase PV and IF have frustrated both clinicians and patients, with little clear progress made over the past 50 years. Treatment modalities with some benefit in chronic myeloid leukemia (CML), such as interferon (IFN), have been used to shrink the massive organomegaly seen in these patients and to improve their marrow function, but are not curative, and not all patients respond or can tolerate the agent. A curative approach is allogeneic peripheral hematopoietic stem cell transplantation. The preparative regimens used in fully ablative techniques rule out older patients for consideration, and many younger patients with good prognostic criteria may do sufficiently well on medical treatment or observation to avoid transplantation. Older patients may have the option to undergo a human leukocyte antigen (HLA)-identical sibling transplant using a reduced intensity preparative regimen in order to minimize peritransplant mortality. Thus a prerequisite to the broad use of transplantation is objective determination of candidacy. Several evaluation methods agree that anemia, age, and cytogenetic abnormalities all predict poor survival in IF, suggesting that patients with anemia and an abnormal karyotype are the prime candidates for allogeneic transplantation. Experimental peripheral blood models that may reflect the degree of marrow fibrosis, such as the serum procollagen 3 peptide assay, have been used to determine if they are more informative of patient status than a single, random bone marrow sampling. Marrow fibrosis may be patchy, and thus a marrow biopsy alone without other data about marrow function may be misleading. Considerable long-term success in eradicating fibrosis and restoring normal cytogenetics, normal bone marrow morphology, and normal complete blood cell counts through transplantation has been reported. Many questions remain to be answered, however, before the appropriate role of hematopoietic stem cell transplantation in the setting of both spent-phase PV and IF can be determined.
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PMID:Transplant decision-making strategies in the myeloproliferative disorders. 1268 80

Eighty-three patients with various chronic myeloproliferative disorders [polycythemia vera (PV), essential thrombocytosis (ET), idiopathic myelofibrosis (IMF)] were analyzed for the occurrence of acute myeloid leukemia (AML) and myelodysplasia (MDS) during treatment with hydroxyurea (HU) alone or HU following treatment with busulphan (BU). A total of 58 patients (29 PV, 14 ET, 12 IMF, 3 unclassified) had been treated with HU. Thirty-five of these patients had been treated with HU alone whereas 18 patients had received both HU and BU. The follow-up period was 7.8 years. Twenty-five patients had not been treated with HU. In this patient group, 4 patients had been treated with BU. The follow-up period was 10.5 years. In the HU-treated group (n = 58) 7 patients developed AML and 5 patients MDS. Five of the 12 patients had been treated with HU alone, and 4 patients had received both HU and BU. In the non-HU-treated group (n = 25) 1 patient with PV developed acute myeloid leukemia (AML). This patient had only been treated with phlebotomies. It is concluded that treatment with HU is leukemogenic, with an incidence of AML and MDS of approximately 14% when used alone. The incidence is markedly increased to about 30% when HU is preceded by treatment with BU. HU is not recommended for use in younger patients, in whom non-leukemogenic agents such as alpha-interferon and anagrelide should be used instead.
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PMID:Acute leukemia and myelodysplasia in patients with a Philadelphia chromosome negative chronic myeloproliferative disorder treated with hydroxyurea alone or with hydroxyurea after busulphan. 1294 87

Polycythemia vera is a chronic myeloproliferative disorder characterized by increased red blood cell mass. The resultant hyperviscosity of the blood predisposes such patients to thrombosis. Polycythemia vera should be suspected in patients with elevated hemoglobin or hematocrit levels, splenomegaly, or portal venous thrombosis. Secondary causes of increased red blood cell mass (e.g., heavy smoking, chronic pulmonary disease, renal disease) are more common than polycythemia vera and must be excluded. Diagnosis is made using criteria developed by the Polycythemia Vera Study Group; major criteria include elevated red blood cell mass, normal oxygen saturation, and palpable splenomegaly. Untreated patients may survive for six to 18 months, whereas adequate treatment may extend life expectancy to more than 10 years. Treatment includes phlebotomy with the possible addition of myelosuppressive agents based on a risk-stratified approach. Agents under investigation include interferon alfa-2b, anagrelide, and aspirin. Consultation with a hematologist is recommended.
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PMID:Polycythemia vera. 1515 62

Until now little information is available about bone marrow (BM) angiogenesis in chronic myeloproliferative disorders (CMPDs). Amongst the various immunohistochemical markers for endothelial cells CD34 and CD105 have proven to be most reliable since they exhibit no relevant co-staining. Determination of vascularity has to include pathophysiological aspects of perfusion. Therefore, quantification of the microvascular density (MVD) by the so-called hot spot method has to be improved by parameters that characterize blood flow more properly like microvessel area (luminal distension), shape (form factor), tortuosity, and branching (maximal vessel length). In comparison to the normal BM chronic myeloid leukemia (CML) revealed a significant increase in MVD which was functionally associated with elevated levels of angiogenic cytokines. Structure of vessels was significantly altered by showing an enhanced irregularity of shape and tortuosity and increase in fibers was conspicuously accompanied by a higher degree of MVD. Contrasting the group of patients with Imatinib (STI571) therapy interferon failed to reduce the number of vessels. Following bone marrow transplantation a significant enhancement of the MVD was found in the early post-transplant period, but after about 6 months normalization occurred. Anomalies of microvascular architecture were easily demonstrable by three-dimensional reconstruction and consisted of a complex branching network of irregular shaped sinuses. Chronic idiopathic myelofibrosis displayed a significant increase in the MVD only in the advanced fibrosclerotic stages. This feature was accompanied by an enhanced luminal distension and tortuosity, thus contrasting the prefibrotic and early fibrotic phases of this disorder. Similar to CML a relationship between evolving myelofibrosis and change in vascular architecture was encountered. This feature may present a possible target for future anti-angiogenic therapy. In essential thrombocythemia there is only a mild increase in MVD detectable while in polycythemia vera besides an enlarged number, a luminal dilation due to the densely packed erythrocytes is recognizable. In conclusion, contrasting the usually applied quantification technique more elaborate morphometrical methods are warranted to obtain a better insight into the vascular architecture of the BM. In CMPDs angiogenesis is significantly associated with the evolution of myelofibrosis and may be altered by therapeutic regimens probably due to changes in cytokine release.
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PMID:Bone marrow angiogenesis: methods of quantification and changes evolving in chronic myeloproliferative disorders. 1537 69

Progression to acute myeloid leukemia/myelodysplastic syndromes (AML/MDS) is a possible evolution of polycythemia vera (PV), but whether some patients are at increased natural risk for this complication and how much the contribution of pharmacologic cytoreduction can affect the natural course of the disease remain uncertain. The European Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP) prospective project included 1638 patients with PV. AML/MDS was diagnosed in 22 patients after a median of 2.5 years from recruitment in the study and a median of 8.4 years from the diagnosis of PV. Variables associated with progression to AML/MDS were assessed using different models of multivariate analysis. Older age was confirmed as the main independent risk factor (hazard ratio [HR], 4.30; 95% confidence interval [95% CI], 1.16-15.94; P = .0294), whereas overall disease duration failed to reach statistical significance (more than 10 years: HR, 1.91; 95% CI, 0.64-5.69; P = .2466). Exposure to P32, busulphan, and pipobroman (HR, 5.46; 95% CI, 1.84-16.25; P = .0023), but not to hydroxyurea (HU) alone (HR, 0.86; 95% CI, 0.26-2.88; P = .8021), had an independent role in producing an excess risk for progression to AML/MDS compared with treatment with phlebotomy or interferon.
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PMID:Acute leukemia in polycythemia vera: an analysis of 1638 patients enrolled in a prospective observational study. 1586 73


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