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. Cancer 2008. © 2008 American Cancer Society.