Reduced Intensity Regimen vs Myeloablative Regimen for Myeloid Leukemia or Myelodysplastic Syndrome (BMT CTN 0901)

Patients randomized to RIC will receive one of two regimen types: the combination of
fludarabine (120-180 mg/m^2) and busulfan (less than or equal to 8 mg/kg or IV equivalent)
(Flu/Bu) or fludarabine (120-180 mg/m^2) and melphalan (less than 150 mg/m^2) (Flu/Mel).
Patient randomized to MAC will receive one of three regimens: busulfan (16 mg/kg oral or 12.8
mg/kg IV equivalent) and cyclophosphamide (120 mg/kg) (Bu/Cy); or, busulfan (16 mg/kg PO or
12.8 mg/kg IV) and fludarabine (120-180 mg/m^2) (Bu/Flu); or, cyclophosphamide (120 mg/kg)
and total body irradiation (greater than 1200-1420cGy) (CyTBI). A total of 356 patients (178
to each arm) will be accrued on this study over a period of four years. Patients will be
followed for up to 18 months from transplantation.

Inclusion Criteria:

- Age equal or less than 65 years old and equal to or greater than 18 years old.

- Patients with the diagnosis of MDS or AML with fewer than 5% myeloblasts in the bone
marrow and no leukemic myeloblasts in the peripheral blood on morphologic analysis
performed within 30 days of start of the conditioning regimen enrollment.

- For patients receiving treatment of their MDS or AML prior to transplantation:
a)Interval between the start of the most recent cycle of conventional cytotoxic
chemotherapy and enrollment must be at least 30 days; b)Interval between completing
treatment with a hypomethylating agent or other non-cytotoxic chemotherapy and
enrollment must be at least 10 days.

- Patients must have a related or unrelated bone marrow or peripheral blood donor who is
human leukocyte antigen (HLA)-matched at 7 or 8 of 8 HLA-A, -B, -C and -DRB1 at high
resolution using DNA-based typing.

- HCT-Specific Comorbidity Index Score (HCT-CI) less than or equal to 4.

- Organ function: a) Cardiac function: Ejection fraction greater than or equal to 40%;
b) Hepatic function: total bilirubin less than or equal to 2 times the upper limit of
normal and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less
than or equal to 3 times the upper limit of normal.; c)Pulmonary function: Diffusing
capacity of the lung for carbon monoxide (DLCO) greater than or equal to 40% and
forced expiratory volume in one second (FEV1) greater than or equal to 50% (corrected
for hemoglobin).

- Creatinine clearance greater than or equal to 50mL/min based on the Cockcroft-Gault
formula.

- Signed informed consent.

Exclusion Criteria:

- Prior allograft or prior autograft.

- Symptomatic coronary artery disease.

- Leukemia involvement in the central nervous system (CNS) within 4 weeks of enrollment
for patients with a history of prior CNS leukemia involvement (i.e., leukemic blasts
previously detected in the cerebral spinal fluid).

- Karnofsky Performance Score less than 70.

- Patients receiving supplemental oxygen.

- Planned use of donor lymphocyte infusion (DLI) therapy.

- Patients with uncontrolled bacterial, viral or fungal infections (undergoing
appropriate treatment and with progression of clinical symptoms).

- Patients seropositive for the human immunodeficiency virus (HIV).

- Patients with prior malignancies, except resected basal cell carcinoma or treated
cervical carcinoma in situ. Cancer treated with curative intent greater than 5 years
previously. Cancer treated with curative intent less than 5 years previously will not
be allowed unless approved by the Protocol Officer or one of the Protocol Chairs.

- Females who are pregnant or breastfeeding.

- Fertile men and women unwilling to use contraceptive techniques during and for 12
months following treatment.