title: TPO, but not soluble-IL-6 receptor, levels increase after anagrelide treatment of thrombocythemia in chronic myeloproliferative disorders.
abstract: Anagrelide is often used in the treatment of thrombocythemia in myeloproliferative disease (MPD), but information concerning effects of treatment on cytokines involved in regulation of blood platelet levels is limited. Here, we investigated serum levels of thrombopoietin (TPO) and soluble IL-6 receptor (sIL-6R) in relation to response to treatment with and plasma concentrations of anagrelide. Samples from 45 patients with thrombocythemia due to MPD (ET=31, PV=14), being treated with anagrelide for 6 months, were analyzed for TPO, sIL-6R and anagrelide levels. The mean baseline platelet count was 983x10(9)/L. A reduction of platelets to <600 in asymptomatic or <400 x 10(9)/L in symptomatic patients was defined as a complete remission (CR), a reduction with >50% of baseline as partial remission, and <50% reduction as failure. At 6 months, 35 patients were in CR, 1 had a partial remission and 9 were treatment failures. For all patients, there was an increase in TPO of 44% from baseline; this change was more pronounced for patients with partial remission and failure. sIL-6R levels did not change significantly. There was no correlation between levels of anagrelide and cytokine levels at 6 months, and changes of cytokine levels did not relate to changes of platelet counts. Thus, a pronounced increase of TPO levels after 6 months of anagrelide treatment indicated that this treatment affected a major regulatory mechanism for megakaryocyte and platelet formation in MPD.
authors.affiliation: Hematology Center, Karolinska University Hospital Huddinge, Stockholm, Sweden. jan.palmblad@ki.se
authors.forename: Jan
authors.initials: J
authors.lastname: Palmblad
authors.forename: Magnus
authors.initials: M
authors.lastname: Björkholm
authors.forename: Jack
authors.initials: J
authors.lastname: Kutti
authors.forename: Gerd
authors.initials: G
authors.lastname: Lärfars
authors.forename: Eva
authors.initials: E
authors.lastname: Löfvenberg
authors.forename: Berit
authors.initials: B
authors.lastname: Markevärn
authors.forename: Mats
authors.initials: M
authors.lastname: Merup
authors.forename: Nils
authors.initials: N
authors.lastname: Mauritzson
authors.forename: Jan
authors.initials: J
authors.lastname: Westin
authors.forename: Jan
authors.initials: J
authors.lastname: Samuelsson
authors.forename: Gunnar
authors.initials: G
authors.lastname: Birgegård
mesh_terms: D000328:Adult; D000368:Aged; D006801:Humans; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000097:blood / Q000627:therapeutic use*; D010976:Platelet Count; D011799:Quinazolines / Q000097:blood / Q000627:therapeutic use*; D019947:Receptors, Interleukin-6 / Q000097:blood*; D013922:Thrombocytosis / Q000188:drug therapy*; D013926:Thrombopoietin / Q000097:blood*; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D011799:Quinazolines; D019947:Receptors, Interleukin-6; D013926:Thrombopoietin; C021139:anagrelide