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.

Alternatives, and adjuncts, to prophylactic platelet transfusion for people with haematological malignancies undergoing intensive chemotherapy or stem cell transplantation

“…Thirty-five trials were not RCTs (Bauman 2011; Berstein 2002; Castaman 1997; Dickinson 2014; Elinoff 2014; Frey 2012; Gerrits 2015; Knoefler 2013; Kristensen 1993; Liesveld 2013; Mittelman 2012; Nash 2000; NCT00358540; NCT00472290; NCT00922883; NCT01194167; NCT01328587; NCT01500538; NCT01516619; NCT01550185; NCT01757145; NCT01791101; NCT01957176; NCT01980030; NCT02046291; NCT02323178; Olnes 2012; Palmblad 2008; Svensson 2014; Townsley 2015; Will 2009a; Will 2009b; Wolff 2001; Wu 2014; Xu 2008).…”

Treatment of Essential Thrombocythemia with Anagrelide Is Associated with an Increased Risk of Worsened Kidney Function

“…The first one puts emphasis on the role of thrombopoietin (TPO). After 6 months of applying ANA treatment, Palmblad et al [19] observed significantly increased serum TPO levels that did not depend on dose of medication, its blood level, or the hematological response. On the other hand, Shimody et al found out that a prolonged increase in the serum TPO level in rats results in an increased TGF-β1 concentration and, thus, myelofibrosis and secondary glomerular damage associated with mesangium growth [20].…”

Advances in megakaryocytopoiesis and thrombopoiesis: from bench to bedside

“…The drug may reduce THPO-mediated intracellular signalling events (McCarty et al, 2006). Interestingly, THPO levels have been reported to increase after anagrelide treatment (Palmblad et al, 2008). In some patients, low-dose aspirin may be required to ameliorate microvascular symptoms (Fan et al, 2008;Tefferi, 2012).…”