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)

Phase II study of YNK01 (1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate), a derivative of cytosine arabinoside, on hematological malignancies was conducted by multi-institutional cooperative group. YNK01 was administered orally at dose of 100-300 mg/body/day for more than 2 weeks. The number of registered and evaluated patients were 211 and 156, respectively. Of 23 patients with acute myelogeneous leukemia (AML), 2 complete response (CR), one partial response (PR) were observed (CR + PR: 13.0%). Hypoplastic leukemia (1/4: 25%), acute unclassified leukemia (1/1: 100%). Of 45 patients with MDS, 2CRs, 6 good response (GR) and 5PRs were observed (CR + PR: 28.9%). AML developing after a prior history of MDS (5/17: 29.4%), CML-BC (2/9: 22.2%). Of 19 patients with CML, 9 achieved CR, 3 achieved PR (63.2%). Of 11 patients with polycythemia vera, 4 achieved CR, 5 achieved PR (81.8%). Of 6 patients with essential thrombocytosis, 2 achieved CR, one achieved PR (50%). The major adverse effects included gastrointestinal toxicities such as nausea, vomiting, anorexia, diarrhea, and elevation of GOT and GPT which were tolerable and reversible. This study indicates that YNK01 is a useful agent against acute leukemia and MDS, especially RAEB, RAEB in T, CMMoL.
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PMID:[Phase II study of YNK01 (1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate) on hematological malignancies]. 226 Aug 76

A phase II study of the oral agent methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU tablet) for myeloproliferative disorders was performed. Fifty-two patients were treated with MCNU tablets and 43 patients were evaluated for clinical effects and 45 for adverse effects. The standard regimen was as follows; oral administration of 50mg (one tablet)/body/day every 4-6 days was considered as one course, and this was repeated at 6-8-week intervals if possible, with certain modifications according to dosage, period of administration and dose interval wherever necessary. Of 16 patients with chronic myelogenous leukemia (CML) in the chronic phase, 13 achieved complete remission (CR), and 3 achieved partial remission (PR). The overall response ratio was 100%. Rapid reduction of leucocytes was detected within two weeks. One patient with CML in blast crisis achieved PR (100%). Of 15 patients with polycythemia vera, 13 showed an excellent effect (87%), and 1 a moderate effect (6.7%), the overall response ratio being 93%. In essential thrombocythemia, an excellent effect (70%) was obtained in 7 of 10 patients. One patient with myelofibrosis showed an excellent effect (100%). Nausea & vomiting (33%) and anorexia (13%) were major adverse effects, but these symptoms were observed only transiently. Liver dysfunction was also seen in 8.9% of patients, but no patient showed severe manifestations. Our study supports the contention that MCNU tablet is a useful agent against myeloproliferative disorders.
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PMID:[Phase II study of a new nitrosourea derivative, MCNU, in tablet form. Takai Blood Cancer Study Group]. 356 4

Sixty-seven patients with hematological malignancies and 4 with cancers were evaluated in this study. Standard administration of MCNU was instituted intravenously using 50-100 mg/m2 every 2 or 4 weeks, whereas some cases were treated with a higher dose therapy. Of 10 patients with chronic myelogenous leukemia, 7 achieved complete remission (CR), and 1 achieved partial remission (PR). A good response was also obtained in 9 of 10 patients with polycythemia vera and in all 4 patients with essential thrombocythemia. MCNU was less effective in malignant lymphoma (ML) and multiple myeloma (MM) than in myeloproliferative disorders. Two of 15 patients with ML and one of 21 patients with MM achieved CR, and two with ML and three MM achieved PR. Three patients with lung cancer and 1 with gastric cancer showed no response to MCNU. Delayed anemia, leukocytopenia and thrombocytopenia were observed in 38.7% of patients, and these were regarded as major side effects of MCNU. Nausea, vomiting, anorexia and elevated transaminase were also found in about 24% of patients, but only transiently. Our study indicates that MCNU is useful for chemotherapy of hematological malignancies, especially of myeloproliferative disorders. Therefore, further studies on combination chemotherapy with MCNU should be developed.
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PMID:[Phase II study of methyl 6-[3-(2-chloroethyl)-3-nitrosoureido]-6-deoxy-alpha-D-glucopyranoside (MCNU)]. 385 48

An autopsy case of erythremia with sideroblastic tumor cell proliferation is described. A 60-year-old man was admitted to the hospital due to general fatigue and anorexia. Bone marrow aspiration revealed abnormalities in erythropoiesis (megaloblasts, 4%; sideroblasts, 84%; ring-formed, 39%, and PAS-positive, 5%). Therapy was directed to pulmonary tuberculosis. Anemia was not improved despite repeated whole blood and platelet transfusions. Serum iron and percentage saturation of the total iron-binding capacity rose during the course. Administration of vitamin B12, B6 or folic acid was inefffective. INAH was replaced by its derivative, IHMS, during the course, but the population of sideroblasts especially of ring-sideroblasts was invariably large (78%-100% and 39%-65% for total sideroblasts and ring-sideroblasts, respectively). He died with increasing abdominal pain and jaundice after three months' hospitalization. Main autopsy findings were: diffuse proliferation of atypical erythroblasts in the bone marrow, systemic lymph nodes, liver, spleen and kidneys. Most of the cells positively stained with iron. Tuberculosis of lungs with cavity formation. Discussion is focussed on the relationship between erythremia and sideroblastic anemia.
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PMID:Erythremia with special reference to sideroblastic anemia. 693 66

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

Polycythemia vera (PV) and essential thrombocythemia (ET) are chronic disorders for which there are no medical cures. Clinical sequelae of PV and ET fall into three categories: primary, such as thrombosis and hemorrhage; secondary, resulting from disease progression or treatment. The decision whether to treat the patient is based on the sequelae of no treatment versus short- and long-term toxicities of the three classes of drugs available for treatment: hydroxyurea, interferon-alpha, and anagrelide. Thrombosis is the most common short-term sequelae of untreated disease; the risk increases with age and after the first thrombotic complication. Hydroxyurea, a nonalkylating myelosuppressive agent, is mutagenic and probably leukemogenic over 5 to 15 years, which makes it unsuitable for treating most younger patients. Interferon-alpha, a cytokine that is myelosuppressive and immunomodulatory, has been shown to have a therapeutic effect in both PV and ET. Tolerance to the initial flu-like symptoms of interferon-alpha is usually developed, but dose-limiting symptoms of anorexia, asthenia, and neuropsychiatric disease can occur, along with exacerbation or development of autoimmune diseases. Anagrelide, a quinazoline that inhibits cyclic nucleotide phosphodiesterase, inhibits platelet aggregation and has an idiosyncratic effect of inhibiting megakaryocyte maturation and platelet budding at doses below those that affect platelet function. This agent is a vasodilator with positive inotropic activity and a side-effect profile that may include palpitations, forceful heartbeat, tachycardia, and headache. One in four patients develop fluid retention and/or edema that are controllable with diuretic therapy. Dizziness is frequent, but mild. Because these side effects usually abate in 2 to 4 weeks, successful management of patients taking anagrelide depends on encouraging them to maintain therapy. The availability of these three classes of drugs with differing modes of action suggests that combination therapy may offer the opportunity to achieve better control of proliferation while reducing short-term side effects as well as the risks of dose-related cumulative sequelae.
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PMID:Other secondary sequelae of treatments for myeloproliferative disorders. 1209 54

Hydroxyurea (HU) is a ribonucleotide reductase inhibitor used to treat myeloproliferative diseases including polycythemia vera (PV) and essential thrombocythemia (ET). We describe an 82-year-old male who was started on HU 500 mg three times weekly for the treatment of PV. Eight days after initiation of HU he experienced anorexia, nausea, vomiting, fever, fatigue, dizziness, and shaking chills. Discontinuation of the HU resulted in resolution of his symptoms within 2 days, and HU was re-started. Ten days after re-starting HU, the patient re-presented with nausea and anorexia. Lab tests revealed elevations in liver enzyme function tests, which resolved promptly after cessation of HU. Patients being initiated on HU should be advised that rarely, fevers, chills, nausea, and elevations in liver function tests may occur.
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PMID:Hydroxyurea induced acute elevations in liver function tests. 1833 43

Myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET) are referred to as the classic Philadelphia chromosome (BCR-ABL1)-negative myeloproliferative neoplasms. Although each has distinct pathologic features, all 3 display alterations in Janus kinase (JAK) signal transduction activator of transcription signaling. Myelofibrosis is the most serious of the 3, associated with shortened survival (median survival, 5-7 years); bone marrow failure with anemia; progressive splenomegaly; and chronic, burdensome symptoms, including fatigue, night sweats, itching, abdominal discomfort, loss of appetite/early satiety, unintentional weight loss, and bone, chest, and abdominal pain. Treatments for MF have been mainly palliative, with the exception of allogeneic stem cell transplantation, which, although potentially curative, is feasible only in a small subpopulation of patients. In November 2011, ruxolitinib, an inhibitor of JAK1 and JAK2, was approved by the US Food and Drug Administration for the treatment of intermediate- or high-risk MF, including primary MF, post-PV MF, and post-ET MF. In clinical trials, ruxolitinib was shown to reduce spleen volume and improve MF-related symptoms and quality-of-life measures. Evidence also suggests that ruxolitinib therapy has a survival advantage over placebo and best available therapy. Thrombocytopenia and anemia were the most common adverse events with treatment. Ongoing trials are assessing the efficacy and safety of ruxolitinib therapy in patients with PV and ET.
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PMID:Ruxolitinib: an oral Janus kinase 1 and Janus kinase 2 inhibitor in the management of myelofibrosis. 2339 78

BCR-ABL-negative myeloproliferative neoplasms include primary myelofibrosis, polycythemia vera, and essential thrombocythemia. Clonal stem cell proliferation and dysregulated JAK/STAT molecular pathways characterize these hematologic malignancies. Symptoms experienced by patients are heterogeneous including excessive and disabling fatigue, early satiety, anorexia, pruritus, bone pain, night sweats, cachexia, abdominal pain and discomfort, and cognitive complaints. Patients also experience impaired quality of life along with decreased overall survival. New targeted drug therapies, including JAK2 inhibitors, have demonstrated remarkable success in alleviating the myeloproliferative neoplasm (MPN) symptomatic burden, reducing splenomegaly and improving quality of life while offering overall survival benefit. Within the USA, FDA approval has only been granted to use JAK2 inhibitors in intermediate- to high-risk myelofibrosis. However, given that low-prognostic-scoring patients have been shown to have considerable symptomology, there is a possibility that lower-risk patients may benefit from therapy. More than ever, the need for accurate MPN symptom burden assessment and subsequent addition of targeted therapies is critical in the treatment of MPNs. This article discusses the role of MPN symptom burden and quality of life as therapeutic targets in the context of recent MPN clinical advances.
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PMID:Quality of life in MPN comes of age as a therapeutic target. 2526 10

Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) are clonal stem cell-derived malignancies that include primary myelofibrosis, polycythemia vera and essential thrombocythemia and are characterized by dysregulated Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling. Clinical manifestations include splenomegaly, cytopenias and/or systemic inflammation. Patients have a heterogeneous symptom profile that includes fatigue, loss of appetite, pruritus and night sweats, which significantly impact quality of life (QoL) and lead to poor survival outcomes. With the introduction of JAK inhibitors, improvement in disease-related symptoms has emerged as a realistic expectation of therapy and an integral measure of clinical efficacy. The JAK1/JAK2 inhibitor ruxolitinib is approved for the treatment of myelofibrosis and is currently under clinical development for polycythemia vera. Ruxolitinib has demonstrated significant reductions in symptom burden, with consequent improvements in QoL measures. With the potential to improve QoL, recognition of the impact and burden of symptoms on patients with MPNs is critical.
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PMID:Reducing symptom burden in patients with myeloproliferative neoplasms in the era of Janus kinase inhibitors. 2564 46


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