Treatment of patients with high-risk myelodysplastic syndromes

SummaryMedian survival is about one year in MDS patients with an unfavourable risk profile. The only curative approach, allogeneic stem cell transplantation, achieves long-term remissions in 30–50% of the few patients eligible for this kind of treatment. Non-myeloablative conditioning, causing less toxicity and treatment-related mortality, has increased the number of transplantation candidates. However, because of an increased risk of relapse, superiority in terms of long-term benefit has not yet been established. Another open question relates to whether induction chemotherapy should be performed prior to allografting in patients with an elevated medullary blast count.Induction chemotherapy followed by consolidation chemotherapy results in long-term remission rates of 15–20%. Standard regimens employ cytarabine in combination with an anthracyclin. It is not advisable to administer induction chemotherapy to MDS patients over 60 years of age who have an unfavourable karyotype, because of low remission rates and a high risk of early relapse. Such patients should be considered candidates for epigenetic treatment. The demethylating agents 5-azacytidine and decitabine have been approved for MDS treatment in the USA since treatment results are superior to best supportive care regarding haematological improvement, risk of leukaemic transformation, and overall survival. Epigenetic treatment, which aims to antagonize abnormal gene silencing, may be augmented by including inhibitors of histone deacetylases. Patients with a high-risk karyotype including a 5q- anomaly should receive a trial of lenalidomide because of impressive responses seen in this cytogenetic subgroup. Thalidomide and farnesyltransferase inhibitors can also be of clinical benefit in a number of high-risk patients.