Fludarabine-IV Busulfan ± Clofarabine and Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)

Inclusion Criteria:

1. Patients must have one of the following hematologic malignancies: a) Acute myeloid leukemia (AML) any stage and cytogenetic risk-group with the only exception being that patients with AML and favorable cytogenetics (t(8;21, inv 16, or t(15;17) who achieve complete remission with one course of induction chemotherapy are not eligible . Patients with treatment related AML are eligible. b) Myelodysplastic syndromes (MDS) with intermediate or high risk International Prognostic Scoring System score (IPSS scores) or treatment related MDS. Patients with low risk MDS are eligible if they fail to respond to hypomethylating agent therapy such as azacitidine or decitabine.
2. Age 3-70 years old. Eligibility for pediatric patients will be determined in conjunction with an MDACC pediatrician.
3. Performance score of \>/= 60 by Karnofsky or PS 0 to 2 (ECOG) (age \> 12 years), or Lansky Play-Performance Scale \>/= 60 or greater (age \<12 years).
4. Negative Beta HCG test in a woman with child bearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization. Women of child bearing potential must be willing to use an effective contraceptive measure while on study.
5. Adequate major organ system function as demonstrated by: Left ventricular ejection fraction of at least 40%.
6. Pulmonary function test (PFT) demonstrating a diffusion capacity of least 50% predicted. For children \</=7 years of age who are unable to perform PFT, oxygen saturation \>/=92% on room air by pulse oximetry.
7. Creatinine \< 1.5 mg/dL. If question about renal function discuss with study chairman and do 24 hour creatinine clearance (clearance should be \>50 ml/min).
8. Bilirubin \< to 2.0 x normal (except Gilbert's Syndrome). SGPT (ALT) \< 200. No evidence of chronic active hepatitis or cirrhosis.
9. Histocompatible stem cell donor: Patients must have an HLA matched related or unrelated donor (HLA A, B, C and DR) willing to donate for allogeneic hematopoietic transplantation. High resolution allele level typing is required for donors other than genotypically identical siblings.
10. No uncontrolled infection. Protocol PI or designé will be final arbiter if there is uncertainty regarding whether a previous infection is controlled on appropriate (antibiotic) therapy.
11. Patient or patient's legal representative, parent(s) or guardian able to sign informed consent.

Exclusion Criteria:

1. Positive for HIV, HBsAg, HCV or other viral hepatitis or cirrhosis from any cause.
2. Prior allogeneic or autologous stem cell transplant using a myeloablative busulfan or total body radiation containing conditioning regimen defined as busulfan-based using a total dose of \>/=12 mg/kg given by mouth or \>/=10 mg/kg given IV; or a total-body irradiation (\> 4 Gy).
3. Active or prior CNS leukemia, unless in complete remission for at least 3 months.
4. Previous therapeutic XRT to the liver as part of involved-field radiation.
5. History of serious chronic mental disorder or drug-abuse accompanied by documented problems of compliance with therapeutic programs.
6. Lack of care-giver for the early (100-day) post-transplant period.