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)

Eighteen patients with polycythemia vera who were less than 60 years old received human leukocyte interferon-alpha subcutaneously at a starting dose of 3 MU three times a week. The interferon dose was escalated to 6 MU three times a week if it was well tolerated and disease was not controlled after 3 months of treatment at the lower dose. Hematologic response was defined as complete if the hematocrit was maintained at less than 45% in the absence of phlebotomy and partial if the hematocrit was kept at 45% to 50%, associated with a 50% or greater reduction of phlebotomy requirements; no response was defined as a response less than a partial response. Complete disease control was achieved in 11 patients, with partial control in a further six cases. One patient failed to respond. Median duration of response was 16 months (range 5 to 43 months), with 15 patients still under treatment. Therapy with human leukocyte interferon-alpha significantly improved (p <.01) phlebotomy requirements, the degree of splenomegaly, pruritus scores, iron stores and mean red cell volume values, and platelet and leukocyte counts. Interferon treatment did not produce remarkable side effects and no patient withdrew from the study because of intolerance. We conclude that subcutaneous human leukocyte interferon-alpha is an effective and well-tolerated therapy in the management of polycythemia vera-associated myeloproliferation and pruritus in patients less than 60 years old.
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PMID:Role of human leukocyte interferon-alpha in the treatment of patients with polycythemia vera. 953 37

The therapeutic efficacy of recombinant interferon-alpha (rIFN-alpha) has been evaluated in 7 patients with polycythaemia vera (PV), diagnosed according to the criteria of the Polycythemia Vera Study Group. Six complete responses and one partial response were achieved. Pruritus significantly improved in 80% (4/5) of the cases. Recombinant interferon-alpha had to be discontinued in 1 patient because of grade 3-4 nephrotoxicity according to WHO criteria. rIFN-alpha therapy significantly decreased the phlebotomy requirements and improved the mean corpuscular volume, erythrocyte and platelet counts, pruritus complaints and the degree of splenomegaly (p < 0.05). rIFN-alpha seems to be an effective treatment modality for the myeloproliferation of PV and pruritus complaints.
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PMID:Therapeutic efficacy of recombinant interferon-alpha in polycythaemia vera. 955 56

The 'gold standard' for the treatment of polycythemia vera (PV) is to date undefined. We performed a retrospective analysis to evaluate the outcome of a cohort of PV patients treated with pipobroman (PB) at a single institution during a period of 20 years (November 1971-October 1991). During this period, a total of 366 adult PV patients were diagnosed according to Polycythemia Vera Study Group (PVSG) criteria. Of these, only 199 (54%) were treated with PB: 92 were males and 107 females, median age was 63.0 years (range 25.2-87.3 years). Major clinical characteristics at onset were as follows: 34 (17%) patients had splenomegaly >3 cm below costal margin, 70 (35%) had platelets >600,000/mm3, 79 (40%) had white blood cells >12,000 mm3; 97 (49%) had hypertension, 83 (42%) had minor neurological symptoms (as vertigo, headache, paresthesias), 33 (17%) had pruritus and 27 (13%) had thrombotic features. All patients received PB at the dosage of 1 mg/kg/day until response was achieved (hematocrit value <50% in males and <45% in females). Thereafter treatment was given according to toxicity and maintenance of response. All patients were phlebotomized before starting treatment (mean number of phlebotomies performed: three, range 2-4) and 47 of them received PB when hematocrit value was already reduced at response levels: therefore, while all patients are evaluable for acute and long-term toxicity, only 152/199 (76.4%) patients are evaluable for response to PB. During a median time of 2 months, all these 152 patients achieved the response; as maintenance, 128/199 (64.3%) patients were managed with PB alone and 71/199 (35.7%) patients received phlebotomies occasionally. Sixty-one out of 199 (30.6%) patients developed disease-related complications (25 neurological symptoms, 21 thrombotic complications, 12 cardiovascular problems, three hepatic failures). Eleven (5.5%) patients developed acute myelogenous leukemia (AML) after a median time of treatment of 89 months (range 33-188 months), 11 (5.5%) patients developed myelofibrosis (median time from treatment 71 months, range 31-182 months) and in six (3%) patients cancer occurred (median time from treatment 85 months, range 13-118 months). The cumulative risk of leukemia in PV was 2% (95% CI: 0-4%) and 6% (95% CI: 1-11%) at 5 and 10 years respectively; the cumulative risk of myelofibrosis was 2% (95% CI: 1-5%) and 9% (95% CI: 3-15%) at 5 and 10 years, respectively. As of May 1996, 33 (16.6%) patients are lost to follow-up, 40 (20.1%) are dead and 126 (63.3%) are alive with a median overall survival of 191 months. In conclusion, this retrospective analysis confirms the efficacy and safety of PB in PV patients and its low leukemogenic role; prospective studies are needed to evaluate the real impact of PB in the treatment of PV.
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PMID:Polycythemia vera treated with pipobroman as single agent: low incidence of secondary leukemia in a cohort of patients observed during 20 years (1971-1991). 963 13

The chronic myeloproliferative syndromes are bone marrow stem cell disorders. An increase of cell counts of one or rather all three blood cell types is characteristic for these disorders. The most important diseases in this group are: chronic myelogenous/granulocytic leukemia, polycythemia rubra vera, osteomyelosclerosis or agnogenic myeloid metaplasia and essential thrombocythemia. The cells are normally differentiating in these diseases, while the control of cell dividing is abnormal and therefore the cells are produced and accumulated in excess. Splenomegaly is a common and characteristic clinical finding. The fibrotic or sclerotic transformation of the bone marrow can take place in all forms of the syndrome. Extramedullary haematopoiesis can occur in all of the above diseases, but it is most common in myelofibrosis/agnogenic myeloid metaplasia. In the last phase of the disease a terminal blastic crisis may terminate the course of chronic myeloproliferative diseases. The myeloproliferative disorders can be transformed in each other--the most common transformation is that of the polycythemia rubra vera into myelofibrosis. The greatest progress in the therapy of chronic myeloproliferative diseases is achieved in chronic myelogenous leukemia: bone marrow transplantation and interferon treatment (the latter also in essential thrombocythemia and polycythemia rubra vera) are routine modalities worldwide. A new drug, anagrelide is effective in the treatment of myeloproliferative thrombocytosis and thrombocythemia.
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PMID:[Chronic myeloproliferative diseases]. 971 44

Previously we described activating mutations of hbetac, the common signaling subunit of the receptors for the hematopoietic and inflammatory cytokines, GM-CSF, IL-3, and IL-5. The activated mutant, hbetacFIDelta, is able to confer growth factor-independent proliferation on the murine myeloid cell line FDC-P1, and on primary committed myeloid progenitors. We have used this activating mutation to study the effects of chronic cytokine receptor stimulation. Transgenic mice were produced carrying the hbetacFIDelta cDNA linked to the constitutive promoter derived from the phosphoglycerate kinase gene, PGK-1. Transgene expression was demonstrated in several tissues and functional activity of the mutant receptor was confirmed in hematopoietic tissues by the presence of granulocyte macrophage and macrophage colony-forming cells (CFU-GM and CFU-M) in the absence of added cytokines. All transgenic mice display a myeloproliferative disorder characterized by splenomegaly, erythrocytosis, and granulocytic and megakaryocytic hyperplasia. This disorder resembles the human disease polycythemia vera, suggesting that activating mutations in hbetac may play a role in the pathogenesis of this myeloproliferative disorder. In addition, these transgenic mice develop a sporadic, progressive neurological disease and display bilateral, symmetrical foci of necrosis in the white matter of brain stem associated with an accumulation of macrophages. Thus, chronic hbetac activation has the potential to contribute to pathological events in the central nervous system.
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PMID:Dysregulated hematopoiesis and a progressive neurological disorder induced by expression of an activated form of the human common beta chain in transgenic mice. 983 20

Two cases of polycythemia vera (PV) had transition to a hematological condition compatible with chronic neutrophilic leukemia (CNL) 17 and 8 years after diagnosis, respectively. One patient was treated with carboquone followed by hydroxyurea (HU) and the other with HU during PV phase. On transition, both had neutrophilia with white blood cell count above 40,000/microl, elevated neutrophil alkaline phosphatase activity, splenomegaly, normal karyotype without bcr-abl rearrangement. Busulfan was temporally effective in controlling the neutrophil count. However, one patient progressed to the so-called spent phase and the other subsequently had multiple transitions between PV and CNL. These cases may represent a form of uncommon evolution of PV and support the contention that CNL is a type of myeloproliferative disorder and that at least some CNL cases have derangement at the hematopoietic stem cell level.
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PMID:Transition of polycythemia vera to chronic neutrophilic leukemia. 1019 40

Of 43 elderly patients who were suspected to have polycythemia between October 1990 and July 1998, 12 patients showed an increased red cell volume measured by 51Cr-labeled red blood cells. We analyzed the clinical characteristics of the 12 patients consisted of 7 men and 5 women, with a median age of 71 (range: 57-92). Chief complaints were headaches and dizziness (3 cases), symptoms of other conditions than polycythemia (4 cases). Five patients had no symptoms. Five of 6 patients over 70 years old had no symptoms due to polycythemia. Seven cases (58%) showed splenomegaly and three cases (25%) showed hepatomegaly. Laboratory findings were as follows: WBC 9.7 +/- 3.9 x 10(3)/microliter (mean +/- SD, p < 0.02 vs normal control), Hb 17.9 +/- 4.2 g/dl (p < 0.001), Plt 39.7 +/- 26.0 x 10(4)/microliter, EPO 13.8 +/- 5.2 mU/ml (p < 0.0001), NAP score 258 +/- 114, Vit. B12 1,686 +/- 2,156 pg/ml, arterial O2 saturation more than 92% in all cases. The diagnosis of all cases was polycythemia vera according to the diagnostic criteria of Polycythemia Vera Study Group. Associated conditions included 8 cases of thrombosis (cerebral thrombosis 4, thrombophrebitis 2, myocardial infarction 1, ischemic colitis 1) and 3 cases of malignancy (esophageal cancer 1, breast cancer 1, renal cancer 1), none of which was therapy-related cancer. Six patients (50%) had only phlebotomy, three (25%) only chemotherapy, and three (25%) both phlebotomy and chemotherapy. Patients over 80 years old needed neither intensive nor continuous treatment. Only one patient died due to esophageal cancer at age 89.
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PMID:[Clinical characteristics of polycythemia vera in the elderly]. 1041 May 70

The term 'erythrocytosis' has advantages over 'polycythaemia' to describe patients with a raised haematocrit (PCV) and deserves to be more widely used. Measurement of red cell mass (RCM) and its relation to that expected for an individual's height and weight permits initial subdivision of erythrocytosis into absolute (increased RCM) or apparent normal RCM. Absolute erythrocytosis may be primary (intrinsically abnormal marrow erythropoiesis) or secondary (increased erythropoietin drive in response to pathological events outside the bone marrow). Both primary and secondary erythrocytosis may be either congenital or acquired. Idiopathic erythrocytosis is a third, probably heterogenous, group within the absolute erythrocytoses. Familial abnormalities of the erythropoietin receptor underlie the primary congenital subgroup. Polycythaemia vera (PV), the clonal myeloproliferative disorder, is so far, the only primary acquired disorder. Newer diagnostic investigations such as serum erythropoietin estimation, improved karyotypic analysis, in vitro culture of erythroid colonies and estimation of spleen size before splenomegaly is palpable, have permitted some modification of the traditional diagnostic criteria of polycythaemia vera. This may allow more confident diagnosis and, together with improved testing for causes of secondary erythrocytosis, may reduce the number of patients so far unsatisfactorily consigned to the idiopathic erythrocytosis group.
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PMID:The classification and diagnostic criteria of the erythrocytoses (polycythaemias) 1079 8

Interferon alpha (IFN) inhibits the growth of the abnormal clone in patients with myeloproliferative disorders, leading to a reduction of the clinical and laboratory signs of the pathologic myeloproliferation. The therapeutic efficacy of IFN in polycythemia vera (PV) is demonstrated by the summarized treatment results of 279 patients participating in 16 prospective nonrandomized studies and in three case reports. The initial IFN dose ranged from 3 to 35 million IU/week. In 82% of the patients the frequency of phlebotomies was reduced. In 50% a complete remission was achieved, defined as a stable hematocrit of 45% without concomitant phlebotomies. Reduction of splenomegaly was seen in 77% and control of pruritus in 81% of the patients. The median observation time of the studies was 13 months (ranging from 3 to 84 months). Individual cases were followed for up to 126 months. In 21% of the patients IFN was terminated, owing mostly to side effects. The selective suppression of the malignant clone by IFN was demonstrated by the induction of cytogenetic remissions in sporadic cases with a chromosomal marker and by the observation of unmaintained remissions that lasted up to 4.8 years. IFN has no known mutagenic or teratogenic effects. The data presently available demonstrate that IFN is an effective alternative to the present forms of treatment in PV. Controlled prospective studies are essential to clarify whether the favorable biologic properties are also reflected by a benefit in clinical course and survival, and whether IFN may reduce the rates of acute leukemia and myelofibrosis. A randomized study that compares IFN and hydroxyurea in patients with PV has recently been initiated by the Suddeutsche Hamoblastosegruppe (SHG) in Germany.
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PMID:Interferon alpha in the treatment of polycythemia vera. 1080 30

A 61-year-old woman, who was diagnosed in 1982 as having polycythemia vera, was admitted to our hospital in July 1998 because of a splenic tumor in an enlarged spleen due to myelofibrosis. As it was difficult to identify the etiology of the splenic tumor, partial splenectomy was carried out. The resected tumor proved to be an extremely proliferative lesion as the result of extramedullary hematopoiesis. Since it is difficult to diagnose the etiology of splenic tumor, the collection and analysis of reports of relevant cases may well facilitate diagnosis.
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PMID:Tumor-like splenic extramedullary hematopoiesis in a patient with myelofibrosis. 1083 Jan 86


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