Anagrelide for thrombocytosis in myeloproliferative disorders

Abstract

The ectodermal dysplasias (ED) are a large and complex group of diseases characterized by anomalies of the ectoderm and its derivates, often associated with malformations in other organs. We report a patient with an ectodermal dysplasia affecting hair, teeth, and nails and malformations of all four extremities including absence of several rays in the hands and feet. This patient shares many similarities with odontotrichomelic syndrome, a rare ectodermal dysplasia syndrome that has so far only been described in three individuals. However, some differences exist and this patient might also represent a separate ectodermal dysplasia syndrome. p63, a gene that is mutated in a number of syndromes associated with ectodermal dysplasia and limb malformations, was considered a possible candidate gene. However, no mutation in p63 was identified. © 2003 Wiley‐Liss, Inc.

Long-term management of thrombocytosis in essential thrombocythaemia

“…It reduces platelet production by inhibiting megakaryocyte colony development, thus reducing megakaryocyte size, ploidy and maturation [63]. Several studies have shown that it effectively lowers platelet counts (overall response rate of 76-94%) and reduces ET-associated complications and symptoms [63][64][65][66][67][68][69][70][71][72]. Anagrelide has been shown in trials to be as effective as hydroxycarbamide, interferon-α and alkylating agents in reducing platelet counts, without the added complication of alkylating or cytotoxic properties [73], and can be used in patients who are intolerant or resistant to these cytoreductive agents [64].…”

“…The ANAHYDRET study demonstrated non-inferiority of anagrelide (for efficacy and ET-related complications) compared with hydroxycarbamide for the treatment of ET patients at 12 months follow-up (p<0.025) [34]. Furthermore, in a study of 79 patients with ET, anagrelide significantly reduced the rate of major thromboembolic complications compared with the pre-treatment period (p=0.0455) [65]. However, a clear clinical benefit in terms of haemorrhagic events has not yet been convincingly demonstrated.…”

“…The most common side effects of anagrelide include headache (13-35%) and tachycardia (9-21%), which arise due to the inhibitory properties of anagrelide on phosphodiesterase III [65,66,69,70,73,77]. The majority of common side effects are mild or moderate (e.g.…”

“…In several studies, the majority of side effects with anagrelide occurred within 1 month of starting therapy [65,66,68,70,71], with evidence showing that they subsided during continued treatment [65-71, 77, 80]. This effect is clearly Resistance/intolerance to hydroxycarbamide requires fulfilment of at least one of the following criteria:…”

The Mevalonate Pathway as a Therapeutic Target in the Ph-Negative Chronic Myeloproliferative Disorders

“…Both drugs are potentially leukaemogenic -at least when being used sequentially in this patient group [69][70][71]. In younger patients alpha-interferon, PEG-Intron or anagrelide may be useful alternatives [72][73][74][75][76][77]. Since all these agents have side effects -and some even potentially leukaemogenic -several clinical trials have recently been conducted to find alternative and better drug formulations [78][79][80][81][82][83][84][85].…”