Progression of bone marrow fibrosis in patients with essential thrombocythemia and polycythemia vera during anagrelide treatment.

Abstract

Anagrelide is a second-line option for reduction of thrombocythemia in patients with chronic myeloproliferative disorders (CMPDs). A multicenter, open, phase II study of anagrelide treatment in 60 patients during 2 yr was performed by the Swedish Myeloproliferative Disorder Study Group. Adequate bone marrow biopsies were obtained from 53 of the CMPD patients [36 essential thrombocythemia (ET), 16 polycythemia vera (PV), 1 chronic idiopathic myelofibrosis (CIMF)] before treatment and compared with biopsies from 30 healthy volunteers and 34 patients with acute myeloid leukemia (AML). Higher reticulin and hyaluronan (HYA) scores were found before anagrelide therapy in the CMPD patients than in the normal controls (p < 0.001 and p < 0.001, respectively) and AML patients (p < 0.001 and p = 0.011, respectively). At the end of the study 30 CMPD patients were still on anagrelide treatment and in 19 of these patients, all diagnosed as ET (n = 16) or PV (n = 3), pretreatment bone marrow biopsies were compared with follow-up samples. After 2 yr of anagrelide therapy the reticulin and HYA scores were significantly higher than before treatment (p = 0.02 and p = 0.002, respectively). The cellularity was significantly higher (p = 0.014), although the number of megakaryocytes did not change significantly. The increase of reticulin and HYA in the bone marrow after 2 yr of treatment with anagrelide indicated progression of fibrosis. Although anagrelide is a valuable drug for reduction of platelet levels, it seems unable to stop progression of bone marrow fibrosis and hypercellularity in ET and PV.

• Authors: Magnus Hultdin, Gunnel Sundström, Anders Wahlin, Berith Lundström, Jan Samuelsson, Gunnar Birgegård, Anna Engström-Laurent
• Journal: Medical oncology (Northwood, London, England) (Med Oncol) Vol. 24 Issue 1 Pg. 63-70 ( 2007) ISSN: 1357-0560 [Print] United States
• PMID: 17673813 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Fibrinolytic Agents
• Quinazolines
• Reticulin
• Hyaluronic Acid
• anagrelide

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Disease Progression
• Female
• Fibrinolytic Agents (therapeutic use)
• Humans
• Hyaluronic Acid (metabolism)
• Male
• Middle Aged
• Polycythemia Vera (complications, drug therapy)
• Primary Myelofibrosis (drug therapy, etiology)
• Prognosis
• Prospective Studies
• Quinazolines (therapeutic use)
• Reticulin (metabolism)
• Thrombocythemia, Essential (complications, drug therapy)
• Thrombocytosis