Study of Intensity Modulated Total Marrow Irradiation (IM-TMI) in Addition to Fludarabine/Busulfan Conditioning for Allogeneic Transplantation in High Risk AML and Myelodysplastic Syndromes

Inclusion Criteria: 1. Age 18-65 years 2. Patients with AML or MDS who meet the following criteria: a. Relapsed or refractory AML (including AML in CR2) b. Poor-risk AML in first remission, with remission defined as \<5% bone marrow blasts morphologically: * AML arising from MDS or a myeloproliferative disorder, or secondary AML * Poor risk molecular features including presence of FLT3 internal tandem duplication mutation. * Poor-risk cytogenetics: Monosomal karyotype, complex karyotype (\> 3 abnormalities), inv(3), t(3;3), t(6;9), MLL rearrangement with the exception of t(9;11), or abnormalities of chromosome 5 or 7 c. Primary refractory disease d. MDS with at least one of the following poor-risk features: * Poor-risk cytogenetics including 3q abnormalities, 7/7q minus or complex cytogenetics (\>3 abnormalities) * Current or previous INT-2 or high IPSS score * Treatment-related MDS * MDS diagnosed before age 21 years * Progression on or lack of response to standard DNA-methyltransferase inhibitor therapy * Life-threatening cytopenias, including those requiring regular PRBC or platelet transfusions e. CML with a history of accelerated or blast phase 3. Patients must have a related or unrelated peripheral blood stem cell donor as follows: 1. Sibling donor must be a 6/6 match for HLA-A, -B at intermediate (or higher) resolution and -DRB1 at high resolution using DNA based typing 2. Unrelated donors must be at least 7/8 match at HLA-A, -B, -C and DRB1 at high resolution using DNA-based typing Exclusion criteria: 1. Presence of significant co morbidity as shown by: 1. Left ventricular ejection fraction \< 50% 2. Creatinine clearance \<30ml/min 3. Bilirubin \> 2.0 mg/dL (unless due to Gilbert's syndrome or hemolysis), and ALT and AST \> 5 x ULN 4. FEV1 and FVC \< 50% of predicted or DLCO \<50% of predicted once corrected for anemia f. Karnofsky score \<70 (appendix C) g. Hematopoietic cell transplantation comorbidity index \>3 h. Active viral hepatitis or HIV infection j. Cirrhosis 2. Pregnancy 3. Patients unable to sign informed consent 4. Patient who have previously received radiation to \>20% of bone marrow containing areas. 4\. DONOR ELIGIBILITY AND SELECTION 4.1. Donor Selection Donor evaluation and selection is by standard for normal clinical practice. No study procedures are to be performed on donors. All donors must be willing to donate peripheral blood stem cells and meet institutional or NMDP criteria for donation. The following prioritization will be used when selecting donors: 1. When possible, an HLA compatible sibling will be used as a donor. 2. For patients who do not have an HLA compatible sibling, an unrelated donor will be used 3. 8/8 matched unrelated donors are preferred over single antigen mismatched donors. If more than one potential volunteer unrelated donor is considered suitable further selection of the most suitable donor is at the discretion of the treating physician. The following serves only as a guide for prioritization: 1. Age of donor (18-24 \> 25-34 \> 35-44 \> 45+) 2. Sex and parity of donor (male \> female, nulliparous female \> parous, multiparous female) 3. Cytomegalovirus (CMV) status, if recipient is CMV seronegative (CMV- \> CMV+)