Lenalidomide and Prednisone in Low and Int-1 Myelodysplastic Syndrome (MDS) Non 5q MDS

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 * Documented diagnosis of MDS according Word Health Organization (WHO) that meets International Prognostic Scoring System (IPSS) criteria for Low- to Intermediate-1-risk disease or non-proliferative (white blood count \[WBC\] \< 13,000/uL) chronic myelomonocytic leukemia (CMML) and MDS/myeloproliferative neoplasms (MPN). * Absence of a chromosome 5q deletion by metaphase cytogenetics or fluorescent in situ hybridization (FISH) analysis * Red blood cell (RBC) transfusion-dependent anemia defined as having received ≥4 transfusions of RBCs for hemoglobin (Hgb) ≤ 9.0 g/dl within 56 days of randomization or symptomatic anemia (Hgb ≤ 9.0 g/dl) * No response or progression on prior treatment with epoetin alpha (\> 40,000 U/wk x 6), darbepoetin alpha (≥ 500 mcg q 3 wk x 2) or serum erythropoietin (EPO) concentration ≥ 500 mU/ml * All previous cancer therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least 4 weeks prior to treatment in this study. * Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 at study entry * Laboratory test results within these ranges: Absolute neutrophil count ≥ 500 /mm³; Platelet count ≥ 50,000 /mm³; Creatinine Clearance \> 60 mL/min by Cockcroft-Gault formula; Total bilirubin ≤ 1.5 mg/dl; aspartic transaminase (AST)and alanine transaminase (ALT) ≤ 2 x upper limit of normal (ULN). * Disease free of prior malignancies for ≥ 3 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" of the cervix or breast * Must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®. * Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 milli-international units per milliliter (mIU/mL) within 10 - 14 days prior to and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) 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. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. Exclusion Criteria: * Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing the informed consent form. * Pregnant or breast feeding. (Lactating females must agree not to breast feed while taking lenalidomide). * 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. * Use of any other experimental drug or therapy within 28 days of baseline * Known hypersensitivity to thalidomide * The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs or history of desquamating (blistering) rash while taking thalidomide * Any prior use of lenalidomide * Concurrent use of other anti-cancer agents or treatments * Known positive for human immunodeficiency virus (HIV) or infectious hepatitis, type B or C * Proliferative CMML (WBC ≥13,000/μL) * MDS secondary to treatment with radiotherapy, chemotherapy, and/or immunotherapy for malignant or autoimmune diseases * Prior ≥ grade-2 National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) allergic reaction to thalidomide * Clinically significant anemia due to factors such as iron, B12 or folate deficiencies, autoimmune or hereditary hemolysis or gastrointestinal bleeding * Known HIV-1 positivity * Chromosome 5q deletion * Documented thromboembolic event within the past 3 years