changes to this chromosome indicate a poor prognosis for myelodysplastic syndrome.

6Hence, a subset of patients with poor prognosis benefi t from azacitidine and the drug could be targeted to this group of patients. Subsequent analysis of the study suggests that older patients and those considered as having acute myeloid leukaemia by newer classifi cations (those with 20–30% bone-marrow blasts) also benefi t from the therapy. 7,8 The data establish azacitidine as standard frontline treatment for patients with higher risk myelodysplastic syndromes. As naturally happens once a new breakthrough has been achieved, new challenges emerge. Although the results of the study are of great signifi cance, most patients with myelodysplastic syndromes will still die as a result of their disease. Therefore, new, more eff ective, options perhaps combination epigenetic approaches, 9 need to be studied in randomised trials to improve outcome. Furthermore, the eff ect on survival reported in the present study might be a class eff ect. Recently, a preliminary report of a randomised survival study with decitabine did not show a survival benefi t in a similar population. 10 We need more information from that study before we can put these data in proper context. Finally, now that we are starting to achieve consistent clinical responses and eff ects on survival, we need to worry about the outcome of patients that do not respond or lose response to inhibitors of DNA methyltransferase. A recent report of outcomes in this population of patients suggests that their prognosis is very poor, a median survival of less than 5 months, and that conventional cytarabine programmes do not change the natural course of the disease 11 —this is our next challenge.