Anagrelide: analysis of long-term efficacy, safety and leukemogenic potential in myeloproliferative disorders

• Published in: Leukemia research 2005-05, Vol.29 (5), p.481-491
• Main Authors: Fruchtman, Steven M., Petitt, Robert M., Gilbert, Harriet S., Fiddler, Garrick, Lyne, Andrew
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Anagrelide; Blood Platelets - drug effects; Blood Platelets - metabolism; Child; Child, Preschool; Essential thrombocythemia; Female; Humans; Leukemogenesis; Male; Middle Aged; Myeloproliferative disorders; Myeloproliferative Disorders - drug therapy; Myeloproliferative Disorders - pathology; Platelet Aggregation Inhibitors - therapeutic use; Polycythemia vera; Quinazolines - therapeutic use; Retrospective Studies; Safety; Thrombocytosis; Time Factors
• ISSN: 0145-2126; 1873-5835
• DOI: 10.1016/j.leukres.2004.10.002

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