YOU ARE NOW CONNECTED TO THE TOXLINE (1981 FORWARD, NON-ROYALTY) FILE. ==THROMBOCYTHEMIA== 3 AUTHOR Barbui T AUTHOR Finazzi G AUTHOR Dupuy E AUTHOR Kiladjian JJ AUTHOR Briere J TITLE Treatment strategies in essential thrombocythemia. A critical appraisal of various experiences in different centers. SOURCE Leuk Lymphoma; VOL 22 Suppl 1, 1996, P149-60 (REF: 86) ABSTRACT The therapeutic strategy in patients with Essential Thrombocythemia (ET) is a difficult balance between the prevention of bleeding and thrombotic complications and the risks of drug side effects and toxicity. Major bleeding is rare and seem to be related to higher platelet counts: therefore, a platelet count over 1500 x 10(9)/L is generally regarded as an indication for cytoreduction. Thrombotic complications include microvascular occlusive symptoms, which are reversible with low-dose aspirin, and large vessels thrombosis. The risk of major thrombosis is higher in ET patients aged more than 60 ys. and with previous occlusive event. In this high-risk group, the non-alkylating agent hydroxyurea (HU) significantly reduces the rate of vascular complications and has emerged as the treatment of choice. However, the long-term risk/benefit of HU remains disputed because its leukemogenic potential has not been ruled out. This holds also for other myelosuppressive agents, such as busulphan and pipobroman. Other drugs of particular interest for young patients include recombinant alpha-interferon (IFN) and Anagrelide. Both of them are effective in lowering platelet count, but their efficacy in reducing clinical complications remains to be demonstrated. However, both IFN and Anagrelide have shown to have frequent and clinically important side effects. Thus, further clinical studies are required to establish their role in the strategy of ET patient treatment. 1 AUTHOR Yamamoto K AUTHOR Nagata K AUTHOR Hamaguchi H TITLE [Complete remission of essential thrombocythemia after recovery from severe bone marrow aplasia induced by busulfan treatment] SOURCE Gan To Kagaku Ryoho; VOL 24, ISS 3, 1997, P365-9 ABSTRACT A 63-year-old woman was found to have thrombocythemia and was referred to our hospital for further evaluation in September 1990. Peripheral blood showed platelet 170.0 x 10(4)/microliter, WBC 14,900/microliter and Hb 9.8 g/dl. Bone marrow was hypercellular with increased megakaryocytes and normal karyotype. She was diagnosed as essential thrombocythemia (ET), and treated with 2 mg of busulfan daily for 3 months until her platelet count decreased to 33.1 x 10(4)/microliter. Busulfan was given again for 40 days (a total of 80 mg) in another hospital when the platelet count increased to 71.1 x 10(4)/microliter in September 1991. In December 1991, she was admitted to our hospital because of pancytopenia. Examination of blood revealed platelet 0.4 x 10(4)/microliter, WBC 1,800/microliter and Hb 7.0 g/dl with hypocellular marrow. A diagnosis of busulfan-induced severe bone marrow aplasia was made. We administered metenolone acetate 15 mg and G-CSF 300 micrograms daily. Blood transfusions were given frequently. However, no effect was observed during her hospitalization. After discharge, G-CSF 600 micrograms and erythropoietin 24,000 units were continued twice a week in combination with metanolone acetate. Pancytopenia gradually began to improve as of June 1992, and then trilineage recovery was achieved in March 1994 with platelet 13.3 x 10(4)/microliter, WBC 5,500/microliter and Hb 12.1 g/dl. The platelet count has been within the normal range for more than 2 years after recovery. 4 AUTHOR Carlisle TL TITLE Use of Agrelin for Patients With Thrombocythemia SOURCE FEDRIP DATABASE, NATIONAL TECHNICAL INFORMATION SERVICE (NTIS) ABSTRACT RPROJ/FEDRIP THROMBOCYTHEMIA, HEMORRHAGIC; MYELOPROLIFERATIVE DISORDERS; LEUKEMIA, MYELOID, CHRONIC OBJECTIVES: This study is an open protocol for the use of anagrelide in the treatment of patients with thrombocythemia. The primary objective is to add to the already substantial prospective clinical experience with this drug, while making it available to our patients pending FDA approval, without requiring individual compassionate use applications for each patient. RESEARCH PLAN: Patients with chronic myeloproliferative diseases (polycythemia vera, chronic granulocytic leukemia, and essential thrombocythemia) commonly develop markedly high platelet counts. In some patients thrombocythemia is accompanied by thrombosis or hemorrhage, which can be successfully treated by reducing the numbers of circulating platelets. Use of anagrelide to lower platelet numbers is under study as an alternative to plateletpheresis (unsuitable for long term therapy), or the use of cytotoxic therapy or ionizing radiation (which can cause leukopenia, anemia, and increased risk of carcinogenesis). Anagrelide produces selective reduction in platelet numbers. Of 577 patients reported by the Anagrelide Study Group in 1992, in 396 the platelet count was reduced by 50% or to less than 600,000/ mm3. Side effects included neurologic symptoms (headache), gastrointestinal symptoms (nausea, diarrhea, abdominal pain), and cardiovascular symptoms (fluid retention or congestive heart failure, hypotension, angina). METHODS: Anagrelide will be administered to patients who meet the entry criteria, according to the recommended dosages. They will be monitored as usual for patients with their myeloproliferative disorder, with the quarterly measurement of alanine aminotransferase and bilirubin added during the first year. In some disorders this would not be done quarterly without symptoms to suggest liver dysfunction. FINDINGS: Three patients have continued on study with effective control of platelet counts. One had an upper gastrointestinal hemorrhage due to peptic ulcer while on study, with a normal platelet count. A fourth patient is being enrolled currently. 6 AUTHOR Schechter GP TITLE Anagrelide for the Treatment of Thrombocytemia SOURCE FEDRIP DATABASE, NATIONAL TECHNICAL INFORMATION SERVICE (NTIS) ABSTRACT RPROJ/FEDRIP QUINAZOLINES; POLYCYTHEMIA VERA; BLOOD PLATELETS This protocol permits the compassionate plea use of anagrelide, a quinazolin compound which is an effective platelet lowering agent in patients with essential thrombocythemia and polycythemia vera. The compound is also a vasodilator and also inhibits platelet aggregation and inhibits cyclic AMP phosphodiesterase and the formation of arachidonic acid metabolites. The drug specifically decreases megakaryocyte production of platelets and has been shown to be effective in lowering platelets in 95% of patients with thrombocythemia. Its major side effects relate to its vasodilator and inotropic effects, mainly-dizziness, headache and palpitations--and mild epigastric distress. A small percentage of patients have developed fluid retention and congestive failure. Previously unrecognized heart disease has occasionally been made manifest by the drug. This drug will be offered to patients with symptomatic thrombocythemia who are refractory to hydroxyurea, or in whom very high platelet counts are associated with severe symptoms such as transient ischemic events of the central nervous system which require rapid lowering of the platelet count... 2 AUTHOR Tomiyama J AUTHOR Komeno T AUTHOR Nanki T AUTHOR Kaneko H AUTHOR Kudo H AUTHOR Teratani T AUTHOR Moriya K TITLE [Essential thrombocythemia in pregnancy] SOURCE Rinsho Ketsueki; VOL 34, ISS 12, 1993, P1579-83 (REF: 13) ABSTRACT A 30-year-old woman was admitted to our hospital because of thrombocythemia during pregnancy. Her leukocyte count was 10,000/microliters, Hb was 11.7 g/dl, and platelet count 181.9 x 10(4)/microliter. Bone marrow aspirate showed an increase in megakaryocytes (255/microliters). Both Ph1 chromosome and bcr rearrangement were negative. She was diagnosed as having essential thrombocythemia (ET) with pregnancy, and was treated with aspirin (150 mg/day). Her pregnancy was uneventful, but she was readmitted because of overterm pregnancy. A caesarean section was performed, and a healthy male infant weighing 3,672 g was delivered, with a platelet count of 25.5 x 10(4)/microliter. However, the uterine was atonic, and atonic hemorrhage occurred. Supravaginal hysterectomy was performed. Subsequently, intrabdominal gross hemorrhage occurred, but the bleeding was halved by platelet transfusion. Microscopic examination showed uterine infarction. We suggest that platelet count should be reduced by means of plateletpheresis or interferon-alpha throughout pregnancy with ET.