Combination of 5-azacytidine and thalidomide for the treatment of myelodysplastic syndromes and acute myeloid leukemia.

The treatment of myelodysplastic syndromes (MDS) remains a challenge to the clinician despite recent advances. Many patients will either not respond or will have only limited and/or brief responses to single-agent therapy. Eventually, 30% of patients with MDS will progress and develop acute myeloid leukemia (AML). New strategies are needed for these patients. 5-Azacytidine (AZA) and thalidomide were administered to 40 patients with MDS or AML. AZA was given at a dose of 75 mg/m2 subcutaneously for 5 of 28 days together with thalidomide starting at a dose of 50 mg per day and increasing to 100 mg per. Six patients had refractory anemia (RA), 2 patients had RA with ringed sideroblasts, 10 patients had RA with excess blasts (RAEB), 1 patient had RAEB in transformation, 4 patients had chronic myelomonocytic leukemia, 1 patient had chronic idiopathic myelofibrosis, and 16 patients had AML. Thirty-six patients were evaluable for outcome. A hematologic improvement (HI) was observed in 15 of 36 patients (42%), stable disease was observed in 5 of 36 patients (14%), and 10 of 36 patients (28%) had disease progression. Six patients experienced complete remission (CR), 2 patients experienced an erythroid HI (HI-E), 1 patient experience an absolute neutrophil count HI (HI-ANC), 5 patients experienced a platelet HI (HI-P), and 7 patients had bilineage HI (HI-P and HI-ANC or an HI-E and HI-ANC). It was noteworthy that 9 of 14 patients with AML had a history of prior MDS, 2 of 9 patients achieved a CR, 4 of 9 patients had HI (HI-E and bilineage HI), and 1 patient had stable disease and was continuing treatment. DNA microarray analysis of 8 responders and 4 nonresponders revealed that the genes associated with cellular proliferation had higher expression levels in nonresponders. The current findings indicated that a combination of low-dose AZA and thalidomide was well tolerated and was effective therapy for the treatment of patients with MDS and AML arising from prior MDS.