Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anagrelide is a member of the imidazo (2,1-b) quinazolin-2-one series of compounds, with a powerful antiaggregating effect on platelets. During studies in humans, anagrelide in small doses has produced thrombocytopenia. We therefore evaluated it in the treatment of thrombocytosis, and to date, platelet levels in 15 of 17 patients with primary thrombocythemia, 2 patients with polycythemia vera and thrombocytosis, and 1 patient with chronic granulocytic leukemia and thrombocytosis have been well controlled with the use of this agent. Induction doses of 1.0 to 1.5 mg given orally every six hours have produced a decrease in the platelet count, starting on day 5 and reaching a normal level by day 12. Side effects of anagrelide have been minimal. Maintenance therapy with 1.5 to 4.0 mg a day has continued to control the platelet count in patients for up to 28 months. This new agent appears promising in the treatment of thrombocytosis in patients with chronic myeloproliferative disease.
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PMID:Anagrelide: a new drug for treating thrombocytosis. 336 87

Thrombotic and hemorrhagic events may result from high circulating concentrations of platelets (> 1,000,000/mm3), and measures to reduce the platelet count are indicated in symptomatic or extreme thrombocytosis. The platelet count can be decreased quickly by plasmapheresis, but the effect is transient. Patients with thrombocytosis secondary to a myeloproliferative disease, such as chronic myelogenous leukemia (CML), frequently require more sustained suppression of the platelet count. Hydroxyurea, busulfan, and interferon are used to maintain a lower platelet count but are occasionally ineffective or intolerable. An alternative to these therapies is anagrelide, a quinazolin derivative that was approved by the Food and Drug Administration in March 1997. Because current dosing guidelines for anagrelide are scarce, the dosing method of the Anagrelide Study Group that published the largest study to date on the drug's efficacy in thrombocytosis was followed. Two unexpected episodes of anagrelide-induced thrombocytopenia occurred despite following these dosing methods. This prompted a critical evaluation of the pharmacodynamic response and the appropriateness of anagrelide dosage recommendations. A case of thrombocytosis treated with anagrelide in a patient with CML is described.
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PMID:Precipitous fall in platelet count with anagrelide: case report and critique of dosing recommendations. 962 Jan 21

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of anagrelide are reviewed. Anagrelide is a selective thrombocytopenic agent with FDA-approved labeling for the treatment of essential thrombocythemia. Clinical trials have shown that the drug may have a role in the treatment of other chronic myeloproliferative disorders, including polycythemia vera, chronic myeloid leukemia, and agnogenic myeloid metaplasia. The mechanism by which anagrelide reduces platelet count is not yet clear. The current hypothesis is that anagrelide affects the late (postmitotic) phases of megakaryocyte development. Anagrelide has a large volume of distribution and is extensively metabolized; less than 1% is recovered unchanged in the urine. Plasma half-life after a 0.5-mg dose is 1.3 hours. Anagrelide's efficacy and safety have been evaluated in open-label, noncomparative trials, in which the response rate was 60-93%. Adverse effects include headache, diarrhea, edema, palpitations, and abdominal pain. Patients with renal or hepatic dysfunction need to be closely monitored for signs of toxicity. The recommended starting dosage is 0.5 mg four times a day or 1 mg twice a day, with dosage adjustment to the lowest effective amount required to reduce and maintain platelet count below 600 x 10(9)/L. The wholesale acquisition price for 0.5-mg capsules is $350 per 100. Whether anagrelide will replace hydroxyurea as first-line therapy in some or all patients remains to be determined. Anagrelide is effective in the treatment of essential thrombocythemia and may have a role in the treatment of other myeloproliferative disorders.
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PMID:Anagrelide, a selective thrombocytopenic agent. 978 84

Thrombocytosis is a common clinical condition. Drugs used for thrombocytosis are hydroxy urea, alkylating agents and interferon alpha. We are reporting a case of chronic myeloid leukemia with thrombocytosis who did not respond to hydroxy urea but was controlled with the addition of a new drug anagrelide. Anagrelide is a platelet reducing agent with no serious side effects. It may be the main weapon against thrombocytosis associated with chronic myeloid leukaemia (CML) and essential thrombocytosis in the coming years.
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PMID:Thrombocytosis--report of a case. 1127 86

We report phase II trial results of the use of oral anagrelide hydrochloride for treating 38 patients with hydroxyurea (HU)-resistant thrombocytosis accompanying chronic myeloid leukemia (CML). Anagrelide's efficacy was well established during a phase II study of more than 400 patients with one of the four myeloproliferative disorders: essential thrombocythemia, polycythemia, idiopathic myelofibrosis, and CML. In the last subgroup, there were 114 CML patients with significant thrombocytosis treated with anagrelide. Out of these patients, 38 had symptoms of thrombosis or hemorrhage and had thrombocytosis resistant to HU. They were then treated with anagrelide at an initial dose of 2.0 mg/day, followed by modifications based upon response and toxicity. In all, 71% of these patients responded with platelet reductions of more than 50% in a median time of approximately 4 weeks. The response rate was not influenced by age, gender, or prior thrombosis or hemorrhage. Importantly, the response rate to anagrelide in patients refractory to prior HU was essentially the same as that of the other 76 CML patients. Treatment with anagrelide was well tolerated and without undue toxicity. Reduction of excessive platelet counts by anagrelide sometimes occurring in CML may lead to the prevention of thrombohemorrhagic complications occurring in this clinical setting and is relevant even in those patients in whom imatinib mesylate is primary therapy.
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PMID:Anagrelide is effective in treating patients with hydroxyurea-resistant thrombocytosis in patients with chronic myeloid leukemia. 1551 Feb 7

Appropriate treatment for nonreactive thrombocytosis resulting from a myeloproliferative disorder (MPD) is surrounded by controversy. Although few doubt the association of thrombocytosis with increased risk for life-threatening events such as thrombosis or hemorrhage, or the association between clonal myeloproliferation and the progression to acute leukemia or myelofibrosis, controversy exists regarding the timing and nature of appropriate therapeutic intervention. Studies have shown that treatment with myelosuppressive agents such as chlorambucil, busulfan, radiophosphorus (32P), and hydroxyurea reduces the platelet count. However, investigators have also identified an increased risk of drug-related leukemic transformation. An ideal cytoreductive treatment for long-term use should minimize thrombosis and avoid long-term complications, especially acute leukemia (AL). Anagrelide, an imidazoquinolin, inhibits megakaryopoiesis and more selectively reduces platelet production in humans. A retrospective analysis of an open-label, multicenter, international trial reviewing 3660 anagrelide-treated patients was performed to assess efficacy and long-term safety, specifically potential for increased leukemogenicity. The study included MPD patients with thrombocytosis diagnosed according to Polycythemia Vera Study Group (PVSG) criteria. Of all patients enrolled, 81% had previously received other myelosuppressive agents; of these, 33% were transferred from the original agent to anagrelide due to toxicity and 31% were transferred because of poor platelet control. Over 45% of patients were symptomatic due to thrombocythemia, most commonly vascular sequelae (25%). Dosage was titrated to achieve a platelet count < 600 x 10(9) L(-1) and ideally between 130 and 450 x 10(9) L(-1). The safety cohort of 3660 patients, including 2251 with essential thrombocythemia (ET), 462 with polycythemia vera (PV), and 947 with chronic myeloid leukemia (CML) and other MPDs, was analyzed to establish the incidence of leukemic transformation in patients with ET and PV. From the Safety Population, 12.8% (467/3660) of patients were treated with anagrelide as the sole cytoreductive agent (naive patients). Acute leukemia/myelodysplasia developed in 2.1% of ET patients (47/2251) with a maximum follow-up of 7.1 years. Of the PV patients, 2.8% developed acute leukemia/myelodysplastic syndrome (13/462), with a maximum follow-up of 7.0 years. ET and PV patients who transformed to AL had all been previously exposed to other cytotoxics; there were no ET or PV patients in the study who transformed to AL exposed solely to anagrelide. With maximum follow-up over 7 years, anagrelide achieved platelet control in over 75% of MPD patients and did not increase the conversion to acute leukemia during the treatment duration analyzed. Longer follow-up is required to confirm these important observations regarding the long-term safety of anagrelide.
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PMID:Anagrelide: analysis of long-term efficacy, safety and leukemogenic potential in myeloproliferative disorders. 1575

Chronic myeloid leukemia in blast phase (BP) is resistant to chemotherapy and majority of patients die within 6 months. Inhibitor Bcr-Abl tyrosine kinase imatinib mesylate dramatically improved outcome of patients in chronic phase (CP) and is also effective in BP of CML. The prognosis of patients treated with imatinib in BP is worse than in CP. High platelet counts are often observed at diagnosis or in the subsequent course of the CML in about 25% of patients. Thrombohemorrhagic complications associated with the thrombocythemia may be serious. Anagrelide selectively reduces circulating platelets and is used in treatment of thrombocythemia in chronic myeloproliferative disorders. Efficacy and safety of combination imatinib mesylate with anagrelide was demonstrated in chronic and accelerated phase of CML. No study about the use of imatinib with anagrelide in BP has been found. 51-year-old white man with CML presented in blast phase was followed for 4 years. Imatinib mesylate in dose of 600 mg p.o. qd. was administered after the failure of initial chemotherapy. The patient was treated with imatinib for 45 months, 14.5 months in combination with anagrelide. Partial hematologic response in duration of 33 months was induced by imatinib, cytogenetic response was not reached. Imatinib-resistant thrombocythemia was controlled with anagrelide in dose of 0.5-1 mg p.o. qd. No thrombohemorrhagic complications were observed. The patient tolerated the combination of imatinib and anagrelide well and long-term survival gave him the chance of treatment with the new tyrosin kinase inhibitor (dasatinib).
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PMID:[Combination of imatinib and anagrelide in treatment of chronic myeloid leukemia in blastic phase]. 1709 8

Chronic myeloid leukemia is a clonal expansion of hematopoietic progenitor cells characterized by exaggerated proliferation of granulocytic lineage, with chronic phase, accelerated phase and blast crisis. Accelerated phase and blast crisis may be associated with extramedulary disease. Extramedullary transformation of CML can be determined both in nodal and extranodal sites. Non-Hodgkin lymphoma is rare in chronic myeloid leukemia and may be misdiagnosed as an extramedullary lymphoid blast transformation; the majorities are T-cell lymphomas with an immature thymic phenotype, while peripheral B-cell lymphomas are rarer. We report the case of a 79-year-old woman carrier Ph+ chronic myeloid leukemia who developed at eight months of diagnosis an accelerated phase of CML associated simultaneous with a tumor of soft palate, which was initial considering an extramedullary disease. The patient was treated with specific chemotherapy for accelerated phase of CML (Cytosinarabinoside) + Anagrelide, and reversed to secondary chronic phase of CML, but soft palate tumor persists. The immunohistochemical findings of bone marrow trephine biopsy examination showed chronic phase of CML (negativity for immature cells such as CD34, Tdt) and the biopsy of soft palate tumor and immunohistochemical findings revealed a primitive non-Hodgkin lymphoma (NHL) with medium B-cells (CD20, CD79a positive) and excluding an extramedullary blast crisis (CD34 negative, Tdt negative). Cytogenetic analysis in tumor revealed absence of Philadelphia chromosome. The patient was treated with local radiotherapy for NHL, with a favorable evolution and Hydroxyurea 1 g/day for CML with hematological remission. A localized lymphoid neoplasm may be an extramedullary localized blast crisis of CML or a distinct malignancy, with distinguished therapy and prognosis. A correct diagnosis based on a complex investigation: immunohistochemistry, conventional cytogenetic analysis and fluorescence in situ hybridization (FISH), molecular analysis (Southern blot and RT-PCR) is necessary. Further studies are required to clarify the pathogenetic relationship between chronic myeloid leukemia and non-Hodgkin lymphomas.
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PMID:A case of non-Hodgkin lymphoma in a patient with chronic myeloid leukemia. 2439 14