Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Manuscript
  • Published:

Therapy

Anagrelide is effective in treating patients with hydroxyurea-resistant thrombocytosis in patients with chronic myeloid leukemia

Abstract

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Silver RT . Chronic myeloid leukemia. Curr Opin Oncol 1992; 4: 66–72.

    Article  CAS  Google Scholar 

  2. Silver RT . Chronic myeloid leukemia. Hematol Oncol Clin North Am 2003; 17: 1159–1173.

    Article  Google Scholar 

  3. Ravandi-Kashani F, Schafer AI . Microvascular disturbances, thrombosis, and bleeding in thrombocythemia: current concepts and perspectives. Semin Thromb Hemost 1997; 23: 479–488.

    Article  CAS  Google Scholar 

  4. Michiels JJ . Erythromelalgia and vascular complications in polycythemia vera. Semin Thromb Hemost 1997; 23: 441–454.

    Article  CAS  Google Scholar 

  5. van Genderen PJ, Michiels JJ . Erythromelalgia: a pathognomonic microvascular thrombotic complication in essential thrombocythemia and polycythemia vera. Semin Thromb Hemost 1997; 23: 357–363.

    Article  CAS  Google Scholar 

  6. Barbui T, Cortelazzo S, Viero P, Bassan R, Dini E, Semeraro N . Thrombohaemorrhagic complications in 101 cases of myeloproliferative disorders: relationship to platelet number and function. Eur J Cancer Clin Oncol 1983; 19: 1593–1599.

    Article  CAS  Google Scholar 

  7. Fenaux P, Simon M, Caulier MT, Lai JL, Goudemand J, Bauters F . Clinical course of essential thrombocythemia in 147 cases. Cancer 1990; 66: 549–556.

    Article  CAS  Google Scholar 

  8. Cortelazzo S, Viero P, Finazzi G, D'Emilio A, Rodeghiero F, Barbui T . Incidence and risk factors for thrombotic complications in a historical cohort of 100 patients with essential thrombocythemia. J Clin Oncol 1990; 8: 556–562.

    Article  CAS  Google Scholar 

  9. Wehmeier A, Daum I, Jamin H, Schneider W . Incidence and clinical risk factors for bleeding and thrombotic complications in myeloproliferative disorders. A retrospective analysis of 260 patients. Ann Hematol 1991; 63: 101–106.

    Article  CAS  Google Scholar 

  10. Colombi M, Radaelli F, Zocchi L, Maiolo AT . Thrombotic and hemorrhagic complications in essential thrombocythemia. A retrospective study of 103 patients. Cancer 1991; 67: 2926–2930.

    Article  CAS  Google Scholar 

  11. Trapp OM, Beykirch MK, Petrides PE . Anagrelide for treatment of patients with chronic myelogenous leukemia and a high platelet count. Blood Cells Mol Dis 1998; 24: 9–13.

    Article  CAS  Google Scholar 

  12. Anagrelide Study Group. Anagrelide, a therapy for thrombocythemic states: experience in 577 patients. Am J Med 1992; 92: 69–76.

  13. Best PJ, Daoud MS, Pittelkow MR, Petitt RM . Hydroxyurea-induced leg ulceration in 14 patients. Ann Intern Med 1998; 128: 29–32.

    Article  CAS  Google Scholar 

  14. van Genderen PJ, Leenknegt H, Michiels JJ, Budde U . Acquired von Willebrand disease in myeloproliferative disorders. Leuk Lymphoma 1996; 22 (Suppl 1): 79–82.

    Article  Google Scholar 

  15. Fruchtman SM, Petitt RM, Gilbert HS, Fiddler G, Lyne A, Anagrelide Study Group. Anagrelide: Analysis of long term safety and leukemogenic potential in myeloproliferative diseases (MPDs). Blood 2002; 100: 70a (abstr.).

    Google Scholar 

  16. Tsimberidou AM, Colburn DE, Welch MA, Cortes JE, Verstovsek S, O'Brien SM et al. Anagrelide and imatinib mesylate combination therapy in patients with chronic myeloproliferative disorders. Cancer Chemother Pharmacol 2003; 52: 229–234.

    Article  CAS  Google Scholar 

  17. Fruchtman S, Pettit RM, Gilbert H . Anagrelide therapy significantly reduces disease related symptoms in patients with myeloproliferative disorders. Blood 2003; 102: 32a (abstr.).

    Google Scholar 

  18. O'Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2003; 348: 994–1004.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

I thank Frieda Pearce, PhD, and Ms Carmen Dixon for their assistance in the preparation of this manuscript. This study was supported in part by the United Leukemia Fund, Inc., and the Cancer Research and Treatment Fund, Inc.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to R T Silver.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Silver, R. Anagrelide is effective in treating patients with hydroxyurea-resistant thrombocytosis in patients with chronic myeloid leukemia. Leukemia 19, 39–43 (2005). https://doi.org/10.1038/sj.leu.2403556

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.leu.2403556

Keywords

This article is cited by

Search

Quick links