Busulfan, Melphalan, and Fludarabine Phosphate Followed by Donor Umbilical Cord Blood Transplant in Treating Younger Patients with High-Risk Acute Leukemia or Myelodysplastic Syndrome

Inclusion Criteria

• Matched sibling donor (HLA 8/8) cord blood or marrow, if available, or an unrelated partially HLA matched single umbilical cord blood (UCB) unit
• UCB unit selection: Considering only units containing >= 2 x 10^7 total nucleated cells/kg and >= 1 x 10^5 CD34+ cells/kg: * 1st priority: HLA-mismatch (HLA-A, -B, -DRB1): 4/6 preferred over 5/6, 5/6 preferred over 6/6 * 2nd priority: Anti-HLA antibody testing will be completed per institutional guidelines with preference to UCB units for which the patient does not have donor specific antibodies. However, the presence of donor specific antibodies does not preclude the use of the UCB unit as long as the risks and potential benefits are discussed with the parent or legal guardian and documented. Antibody debulking should be considered * 3rd priority: If above priorities are fulfilled and equal, select the unit with the largest CD34+/kg cell dose * Additional considerations: If all above priorities fulfilled and equal, consider matching on ABO and race (latter when data available)
• Aged =< 3 years at diagnosis (not age of transplant)
• Meeting of one of the following disease criteria: * Acute myeloid leukemia: high risk first complete remission (CR)1 as evidenced by: ** High risk cytogenetics; t(4;11) or other mixed lineage leukemia (MLL) rearrangements; chromosome 5, 7, or 19 abnormalities; complex karyotype (> 5 distinct changes) ** >= 2 cycles to obtain complete remission (CR); CR2 or higher preceding myelodysplasia (MDS) ** All patients must be in CR or early relapse (i.e., < 15% blasts in bone marrow [BM]) * Acute lymphocytic leukemia: high risk CR1 as evidenced by: ** High-risk cytogenetics: t(4;11) or other MLL rearrangements; hypodiploid; t(9;22) ** > 1 cycle to obtain CR ** CR2 or higher ** All patients must be in CR as defined by hematological recovery, AND < 5% blasts by light microscopy within the bone marrow with a cellularity of >= 15% * Myelodysplasia (MDS) International Prognostic Scoring System (IPSS) intermediate (Int)-2 or high risk (i.e. refractory anemia with excess blasts [RAEB], RAEB in transformation [RAEBt]) or refractory anemia with severe pancytopenia or high risk cytogenetics; blasts must be < 10% by a representative bone marrow aspirate morphology * Persistent or rising minimal residual disease (MRD) after standard chemotherapy regimens: patients with evidence of minimal residual disease at the completion of therapy or evidence of rising MRD while on therapy; MRD will be defined by either flow cytometry (> 0.1% residual cells in the blast gate with immune phenotype of original leukemic clone), by molecular techniques (polymerase chain reaction [PCR] or fluorescent in situ hybridization [FISH]) or conventional cytogenetics (g-banding) * New leukemia subtypes: A major effort in the field of pediatric hematology is to identify patients who are of high risk for treatment failure so that patients can be appropriately stratified to either more (or less) intensive therapy; this effort is continually ongoing and retrospective studies identify new disease features or characteristics that are associated with treatment outcomes; therefore, if new high risk features are identified after the writing of this protocol, patients can be enrolled with the approval of two members of the study committee
• Lansky play score >= 50
• Glomerular filtration rate > 60 ml/min/1.73 m^2
• Bilirubin < 5 x upper limit of normal
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 5 x upper limit of normal
• Alkaline phosphatase (ALP) < 5 x upper limit of normal
• Oxygen saturation > 92%
• Left ventricular ejection fraction (LVEF) >= 45%
• Voluntary written informed consent before performance of any study-related procedure not part of normal medical care

Exclusion Criteria

• Active uncontrolled infection at time of transplantation (including active infection with Aspergillus or other mold within 30 days)
• History of human immunodeficiency virus (HIV) infection or known positive serology
• Myeloablative transplant within the last 6 months
• Evidence of active extramedullary disease (including central nervous system [CNS] leukemia)