Lenalidomide and Decitabine in High Grade Myelodysplastic Syndromes

Inclusion Criteria: * Understand and voluntarily sign an informed consent form. * Age \>/=18 years at the time of signing the informed consent form. * Able to adhere to the study visit schedule and other protocol requirements. * Myelodysplastic syndrome (documented by bone marrow biopsy) with IPSS score of Int-2 or High risk. * All previous MDS therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least 28 days prior to treatment in this study. * ECOG performance status of \</= 2 at study entry. * Laboratory test results within these ranges: Serum creatinine \</= 2.5 mg/dL x ULN, Total bilirubin \</= 2.5 mg/dL x ULN, AST (SGOT) and ALT (SGPT) \</= 3 x ULN. * All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®. * Females of childbearing potential must have a negative serum pregnancy test within 10-14 days prior to and again within 24 hours of prescribing lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. Must also agree to ongoing pregnancy testing. * Men must agree to use a latex condom during sexual contact even if they have had a successful vasectomy. * Disease free of prior malignancies for \>/= 3 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, localized prostate cancer, or carcinoma "insitu" of the cervix or breast. Exclusion Criteria: * Any serious medical condition, laboratory abnormality, or psychiatric * Pregnant or breast feeding females. * Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. * Known hypersensitivity or reaction to thalidomide, lenalidomide or decitabine. * Any prior use of lenalidomide. * Concurrent use of other anti-cancer agents or anti-cancer treatments. * Known positive for HIV or active infectious hepatitis, type A, B or C. * History of thromboembolic event within past 6 months prior to enrollment.