Treosulfan, Fludarabine Phosphate, and Total-Body Irradiation Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Myelodysplastic Syndrome, Acute Lymphoblastic Leukemia

Inclusion Criteria:

Acute myeloid leukemia (AML):

All AML patients beyond 1st remission;
Intermediate or high risk AML patients (based on South West Oncology Group [SWOG] cytogenetic criteria) in 1st complete remission
Myelodysplastic syndrome (MDS)
Other myeloid malignancies as chronic myelogenous leukemia (CML), CML accelerated phase, CML blast crisis, chronic myelomonocytic leukemia (CMML) (to be approved by patient care conference [PCC])
With Karnofsky Index or Lansky Play-Performance Scale > 70% on pre-transplant evaluation
Able to give informed consent (if > 18 years), or with a legal guardian capable of giving informed consent (if < 18 years)
Previous autologous or allogeneic HCT is allowed

Donors must be:

Human leukocyte antigen (HLA)-identical related donors or
Unrelated donors matched for HLA-A, B, C, DRB1, and DQB1 defined by high resolution deoxyribonucleic acid (DNA) typing or mismatched for one HLA allele, except for HLA-C where no mismatch is allowed
Able to undergo peripheral blood stem cell collection or bone marrow harvest
In good general health, with a Karnofsky or Lansky Play Performance score > 90%
Able to give informed consent (if > 18 years), or with a legal guardian capable of giving informed consent (if < 18 years)
Acute lymphoblastic leukemia (ALL): all ALL patients not eligible for other protocols

Exclusion Criteria:

Receiving umbilical cord blood
With impaired cardiac function as evidenced by ejection fraction < 35% or cardiac insufficiency requiring treatment or symptomatic coronary artery disease
With impaired pulmonary function as evidenced by partial pressure of oxygen (pO2) < 70 mm Hg and diffusing capacity of the lung for carbon monoxide (DLCO) < 70% of predicted or pO2 < 80 mm Hg and DLCO < 60% of predicted; or receiving supplementary continuous oxygen
With impaired renal function as evidenced by creatinine-clearance < 50% for age, weight, height or serum creatinine > 2x upper normal limit or dialysis-dependent
With hepatic dysfunction as evidenced by total bilirubin or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.0 x upper normal limit or evidence of synthetic dysfunction or severe cirrhosis
With active infectious disease requiring deferral of conditioning, as recommended by an Infectious Disease specialist
With human immunodeficiency virus (HIV)-positivity or active infectious hepatitis because of possible risk of lethal infection when treated with immunosuppressive therapy
With central nervous system (CNS) leukemic involvement not clearing with intrathecal chemotherapy and/or cranial radiation prior to initiating conditioning (day -6)
With life expectancy severely limited by diseases other than malignancy
Women who are pregnant or lactating because of possible risk to the fetus or infant
With known hypersensitivity to treosulfan and/or fludarabine
Receiving another experimental drug within 4 weeks before initiation of conditioning (day -6)
Unable to give informed consent (if > 18 years) or with a legal guardian (if < 18 years) unable to give informed consent

Ineligible donors will be those:

Deemed unable to undergo marrow harvesting or PBSC mobilization and leukapheresis
Who are HIV-positive
With active infectious hepatitis
Females with a positive pregnancy test
Unable to give informed consent (if > 18 years) or with a legal guardian (if < 18 years) unable to give informed consent