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