2 research outputs found
New treatment strategies in myelodysplastic syndromes and acute myeloid leukemia:Hypomethylating agents and proteasome inhibitors
New treatment strategies in myelodysplastic syndromes and acute myeloid leukemia:Hypomethylating agents and proteasome inhibitors
New treatment strategies in leukemia and myelodysplastic syndromesTreatment of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) is challenging, especially in the large group of patients older than 60 years. In these patients, results of standard chemotherapy are often disappointing and many patients are ineligible for this intensive treatment. Therefore, we investigated new treatment strategies for AML and MDS.The first part of this thesis describes the first treatment results of azacitidine in the Netherlands. Azacitidine treatment was feasible in clinical practice and effective in about half of the patients. Even in several poor-risk patient groups with usually no response to chemotherapy, favorable responses to azacitidine or the similar drug decitabine were observed. However, predicting which patients will respond remains difficult. We identified platelet doubling after the first azacitidine cycle as an early sign of response.Results of comparing azacitidine with standard chemotherapy in older AML patients surprisingly showed no difference in survival, while side-effects were more severe after chemotherapy. Therefore, azacitidine may be considered more often in older patients instead of standard chemotherapy.In the second part, we investigated whether proteasome inhibitors, originally developed for treating multiple myeloma, could be effectively targeting AML stem cells. Results showed that the second-generation proteasome inhibitor carfilzomib reduced the amount of AML stem cells while sparing the healthy stem cells. Therefore, carfilzomib might be effective in treating AML and should be further investigated