Inclusion Criteria:

* Diagnosis DS or DS mosaicism by karyotype or chromosomal analysis
* Diagnosis of myelodysplastic syndromes (MDS) with \< 30% blasts or acute myeloid leukemia (AML)

* Newly diagnosed disease
* Patients with a history of transient myeloproliferative disorder (TMD) are eligible provided the patient is diagnosed with AML or MDS at \> 90 days of age AND meets either of the following criteria:

* At least 30% blasts in the bone marrow regardless of time since resolution of TMD
* More than 8 weeks since resolution of TMD with ≥ 5% blasts in the bone marrow
* Immunophenotype required for study entry
* No promyelocytic leukemia
* Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by radionuclide angiogram
* Bilirubin ≤ 1.5 times upper limit of normal (ULN)
* AST or ALT \< 2.5 times ULN
* Creatinine adjusted according to age as follows:

* No greater than 0.4 mg/dL (≤ 5 months)
* No greater than 0.5 mg/dL (6 months -11 months)
* No greater than 0.6 mg/dL (1 year-23 months)
* No greater than 0.8 mg/dL (2 years-5 years)
* No greater than 1.0 mg/dL (6 years-9 years)
* No greater than 1.2 mg/dL (10 years-12 years)
* No greater than 1.4 mg/dL (13 years and over \[female\])
* No greater than 1.5 mg/dL (13 years to 15 years \[male\])
* No greater than 1.7 mg/dL (16 years and over \[male\])
* Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min
* No evidence of dyspnea at rest
* No exercise intolerance
* Pulse oximetry \> 94%
* No prior chemotherapy, radiotherapy, or any antileukemic therapy

* Intrathecal cytarabine therapy given at diagnosis allowed
* Prior therapy for TMD allowed