New consensus: a unified definition of clinical resistance and/or intolerance to hydroxyurea in essential thrombocythaemia.

Abstract

In the treatment of essential thrombocythaemia (ET), cytoreductive agents are used to reduce the risk of thrombosis and other disease-related complications. Hydroxyurea (HU) is the cytoreductive agent most commonly used for the treatment of high-risk ET patients (1). Although the use of HU is supported by evidencebased guidelines (1) and the results of randomised studies (2), it is not an optimal treatment option for all ET patients. It is estimated that 10% of patients receiving it do not achieve the desired reduction in platelet count using recommended doses (clinical resistance) (3). Some patients also experience unacceptable side effects including leg ulcers, other muco-cutaneous manifestations and HU-related fever (clinical intolerance) (1, 2, 4, 5). In such cases, clinicians must decide whether it is appropriate to stop HU therapy and switch to an alternative agent. An important consideration in switching from HU to an alternative ET treatment option is the possible increased risk of leukaemic transformation that may apply if other cytostatic agents are used (6). The putative risk of leukaemia associated with HU therapy prompted the evaluation of other drugs thought to lack leukaemogenic potential such as interferon and anagrelide. In Europe, anagrelide has been approved for ‘at risk patients who are intolerant to their current therapy or whose elevated platelet counts are not reduced to an acceptable level by their current therapy’ (3). This indication highlights clinical intolerance or resistance as the basis for switching a patient’s current therapy to an alternative agent. It does not, however, specify precise criteria for how resistance and intolerance should be defined. The need for a unified definition of resistance and intolerance to hydroxyurea