Thrombocytosis
http://www.100md.com
《新英格兰医药杂志》
To the Editor: We appreciate Schafer's concise approach to thrombocytosis (March 18 issue)1 but are less enthusiastic about promoting anagrelide as first-line therapy for patients with essential thrombocythemia. There have been no controlled trials of anagrelide that show a reduction in thrombotic outcomes. In one case series, a majority of patients had improvement in thrombocytosis, although 20 percent still had thrombotic complications.2 A reduced platelet count is the goal of therapy in essential thrombocythemia only because it is a marker of disease activity. Thus, the therapeutic agent of choice must be selected primarily on the basis of its ability to decrease vascular complications rather than solely on its potency as a platelet-reducing agent.
Currently, hydroxyurea is the only agent for which a controlled trial showed a reduction in thrombotic complications.3 Schafer's concern about the leukemogenicity of hydroxyurea is understandable, though recent research suggests that the elevation in risk from baseline remains to be clarified.4 Clearly, the decisions regarding treatment for high-risk patients with essential thrombocythemia are complicated. Until a definitive comparison of hydroxyurea and anagrelide is reported, a clear first choice remains difficult to define.
Matthew C. Cheung, M.D.
Lisa K. Hicks, M.D.
Jacob Pendergrast, M.D.
University of Toronto
Toronto, ON M5G 2M9, Canada
References
Schafer AI. Thrombocytosis. N Engl J Med 2004;350:1211-1219.
Storen EC, Tefferi A. Long-term use of anagrelide in young patients with essential thrombocythemia. Blood 2001;97:863-866.
Cortelazzo S, Finazzi G, Ruggeri M, et al. Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med 1995;332:1132-1136.
Finazzi G, Ruggeri M, Rodeghiero F, Barbui T. Efficacy and safety of long-term use of hydroxyurea in young patients with essential thrombocythemia and a high risk of thrombosis. Blood 2003;101:3749-3749.
Dr. Schafer replies: I agree with Cheung et al. that anagrelide cannot be considered the clear first choice of treatment for platelet reduction in patients with essential thrombocythemia; I therefore referred to it as "alternative first-line therapy." In the study that Cheung et al. refer to, 20 percent of patients with essential thrombocythemia who were receiving active therapy with anagrelide had major thrombotic events, and 20 percent had major bleeding complications.1 However, all these thrombohemorrhagic episodes occurred when platelet counts were greater than 400,000 per cubic millimeter, suggesting that complete normalization of platelet counts may be needed to prevent these complications, at least in high-risk patients. I also concur that a reduced platelet count cannot yet be accepted as a surrogate for a clinical response. Indeed, the general myelosuppression induced by hydroxyurea, in contrast to the platelet-selective action of anagrelide, may have contributed to its antithrombotic efficacy in the only controlled cytoreduction trial to date.2 Nevertheless, pending controlled head-to-head trials, anagrelide is considered by many to be an alternative first-line treatment in young patients with essential thrombocythemia because of continued concern about the leukemogenicity of hydroxyurea.3
Andrew I. Schafer, M.D.
University of Pennsylvania School of Medicine
Philadelphia, PA 19104
andrew.schafer@uphs.upenn.edu
References
Storen EC, Tefferi A. Long-term use of anagrelide in young patients with essential thrombocythemia. Blood 2001;97:863-866.
Cortelazzo S, Finazzi G, Ruggeri M, et al. Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med 1995;332:1132-1136.
Neilsen I, Hasselbalch HC. Acute leukemia and myelodysplasia in patients with a Philadelphia chromosome negative chronic myeloproliferative disorder treated with hydroxyurea alone or with hydroxyurea after busulphan. Am J Hematol 2003;74:26-31.
Currently, hydroxyurea is the only agent for which a controlled trial showed a reduction in thrombotic complications.3 Schafer's concern about the leukemogenicity of hydroxyurea is understandable, though recent research suggests that the elevation in risk from baseline remains to be clarified.4 Clearly, the decisions regarding treatment for high-risk patients with essential thrombocythemia are complicated. Until a definitive comparison of hydroxyurea and anagrelide is reported, a clear first choice remains difficult to define.
Matthew C. Cheung, M.D.
Lisa K. Hicks, M.D.
Jacob Pendergrast, M.D.
University of Toronto
Toronto, ON M5G 2M9, Canada
References
Schafer AI. Thrombocytosis. N Engl J Med 2004;350:1211-1219.
Storen EC, Tefferi A. Long-term use of anagrelide in young patients with essential thrombocythemia. Blood 2001;97:863-866.
Cortelazzo S, Finazzi G, Ruggeri M, et al. Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med 1995;332:1132-1136.
Finazzi G, Ruggeri M, Rodeghiero F, Barbui T. Efficacy and safety of long-term use of hydroxyurea in young patients with essential thrombocythemia and a high risk of thrombosis. Blood 2003;101:3749-3749.
Dr. Schafer replies: I agree with Cheung et al. that anagrelide cannot be considered the clear first choice of treatment for platelet reduction in patients with essential thrombocythemia; I therefore referred to it as "alternative first-line therapy." In the study that Cheung et al. refer to, 20 percent of patients with essential thrombocythemia who were receiving active therapy with anagrelide had major thrombotic events, and 20 percent had major bleeding complications.1 However, all these thrombohemorrhagic episodes occurred when platelet counts were greater than 400,000 per cubic millimeter, suggesting that complete normalization of platelet counts may be needed to prevent these complications, at least in high-risk patients. I also concur that a reduced platelet count cannot yet be accepted as a surrogate for a clinical response. Indeed, the general myelosuppression induced by hydroxyurea, in contrast to the platelet-selective action of anagrelide, may have contributed to its antithrombotic efficacy in the only controlled cytoreduction trial to date.2 Nevertheless, pending controlled head-to-head trials, anagrelide is considered by many to be an alternative first-line treatment in young patients with essential thrombocythemia because of continued concern about the leukemogenicity of hydroxyurea.3
Andrew I. Schafer, M.D.
University of Pennsylvania School of Medicine
Philadelphia, PA 19104
andrew.schafer@uphs.upenn.edu
References
Storen EC, Tefferi A. Long-term use of anagrelide in young patients with essential thrombocythemia. Blood 2001;97:863-866.
Cortelazzo S, Finazzi G, Ruggeri M, et al. Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med 1995;332:1132-1136.
Neilsen I, Hasselbalch HC. Acute leukemia and myelodysplasia in patients with a Philadelphia chromosome negative chronic myeloproliferative disorder treated with hydroxyurea alone or with hydroxyurea after busulphan. Am J Hematol 2003;74:26-31.