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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Raza
Azra
A
Department of Medicine, St. Vincent's Comprehensive Cancer Center, New York, New York 10011, USA. araza@aptiumoncology.com
Mehdi
Murtaza
M
Mumtaz
Muhammad
M
Ali
Fahad
F
Lascher
Steven
S
Galili
Naomi
N
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001374:Azacitidine / Q000008:administration & dosage*; D001854:Bone Marrow Cells / Q000473:pathology; D004334:Drug Administration Schedule; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000401:mortality; D020411:Oligonucleotide Array Sequence Analysis; D010865:Pilot Projects; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage*; D016896:Treatment Outcome
D013792:Thalidomide; D001374:Azacitidine