Treosulfan, Fludarabine Phosphate, and Total-Body Irradiation in Treating Patients With Hematological Cancer Who Are Undergoing Umbilical Cord Blood Transplant

Inclusion Criteria:

• Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL): Must have < 20% morphologic marrow blasts in an evaluable marrow sample (> 25% of normal cellularity for age) collected less than one month prior to start of conditioning; patients in which adequate marrow/biopsy specimens cannot be obtained to determine remission status by morphologic assessment, but have fulfilled criteria of remission by flow cytometry, recovery of peripheral blood counts with no circulating blasts, and/or normal cytogenetics (if applicable) may still be eligible; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures; these patients must be discussed with the Principal Investigator prior to enrollment; patients persistently aplastic for greater than one month since completing last chemotherapy are also eligible
• Myelodysplastic syndrome (MDS): Any 2001 World Health Organization (WHO) classification subtype; refractory anemia with excess blasts (RAEB)-2 patients may proceed directly to transplant but may also be considered for induction chemotherapy before transplant; patients with >= 20% morphologic marrow blasts require induction therapy to reduce morphologic marrow blasts below 5% before transplant
• Chronic myelogenous leukemia: All types, except refractory blast crisis; chronic phase patients must have failed or been intolerant to Gleevec or other tyrosine kinase inhibitors
• Patients =< 50 must have performance status score: Karnofsky (for adults) >= 70; Lansky (for children) score >= 50
• Patients > 50 must have Karnofsky performance score >= 70 and comorbidity index < 5
• Adequate cardiac function defined as absence of decompensated congestive heart failure or uncontrolled arrhythmia AND left ventricular ejection fraction >= 35% OR fractional shortening > 22%
• Adequate hepatic function; patients with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, histology, and the degree of portal hypertension; patients with fulminant liver failure, cirrhosis with evidence of portal hypertension or bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, or correctable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3mg/dL, and symptomatic biliary disease will be excluded
• Adequate renal function defined as creatinine =< 2.0 mg/dl (adults) or creatinine clearance > 40 ml/min (pediatrics); all adults with a creatinine > 1.2 or a history of renal dysfunction must have estimated creatinine clearance > 40 ml/min
• If recent mold infection, e.g., Aspergillus, must be cleared by infectious disease to proceed
• Second hematopoietic cell transplant: must be >= 3 months after prior myeloablative transplant

Exclusion Criteria:

• Patients =< 65 years with an available 5-6/6 human leukocyte antigen (HLA)-A, B, DRB1 matched sibling donor
• Pregnancy or breastfeeding
• Evidence of human immunodeficiency virus (HIV) infection or known HIV positive serology
• Uncontrolled viral or bacterial infection at the time of study enrollment
• Active or recent (prior 6 month) invasive fungal infection without ID consult and approval
• Central nervous system (CNS) leukemic involvement not clearing with intrathecal chemotherapy and/or cranial radiation prior to initiation of conditioning (day -6)
• AML in first complete response (CR1) with favorable prognostic cytogenetics (t8;21, t15;17, inv16) and low risk MDS (International Prognostic Scoring System [IPSS] score 0)
• Impaired pulmonary function as evidenced by oxygen partial pressure (pO2) < 70 mm Hg and diffusing capacity of the lung for carbon monoxide (DLCO) corrected < 70% or pO2 < 80 mm Hg and DLCO corrected < 60%; or receiving supplementary continuous oxygen