• Incidence of transplant-related mortality (TRM) at 6 months after transplant [ Designated as safety issue: No ]
• Pharmacokinetics of mycophenolate mofetil and fludarabine phosphate in infants [ Designated as safety issue: No ]
• Pattern of chimerism as measured by bone marrow samples on days 21 and 100 and at 6 months, 1 year, and 2 years after transplant [ Designated as safety issue: No ]
• Incidence of platelet engraftment at 1 year after transplant [ Designated as safety issue: No ]
• Incidence of acute graft-versus-host disease (GVHD) grade II-IV and grade III-IV at day 100 after transplant [ Designated as safety issue: No ]
• Incidence of chronic GVHD at 1 year after transplant [ Designated as safety issue: No ]
• Incidence of relapse at 1 and 2 years after transplant [ Designated as safety issue: No ]
• Probability of survival and disease-free survival at 1 and 2 years after transplant [ Designated as safety issue: No ]
• Neuropsychological testing at 1, 2, and 5 years after transplant [ Designated as safety issue: No ]

• Incidence of transplant-related mortality (TRM) at 6 months after transplant
• Pharmacokinetics of mycophenolate mofetil and fludarabine phosphate in infants
• Pattern of chimerism as measured by bone marrow samples on days 21 and 100 and at 6 months, 1 year, and 2 years after transplant
• Incidence of platelet engraftment at 1 year after transplant
• Incidence of acute graft-versus-host disease (GVHD) grade II-IV and grade III-IV at day 100 after transplant
• Incidence of chronic GVHD at 1 year after transplant
• Incidence of relapse at 1 and 2 years after transplant
• Probability of survival and disease-free survival at 1 and 2 years after transplant
• Neuropsychological testing at 1, 2, and 5 years after transplant

RATIONALE: Giving chemotherapy, such as busulfan, fludarabine, and melphalan, before a donor umbilical cord blood stem cell transplant helps stop the growth of abnormal or cancer cells and prepares the patient's bone marrow for the stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil may stop this from happening.

PURPOSE: This phase II trial is studying how well combination chemotherapy followed by a donor umbilical cord blood transplant works in treating infants with high-risk acute leukemia or myelodysplastic syndromes.

OBJECTIVES:

Primary

• Determine the incidence of engraftment, defined as achieving donor-derived neutrophil count > 500/mm³ by day 42, in infants with high-risk acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndromes treated with a non-irradiation containing myeloablative conditioning regimen comprising busulfan, fludarabine, and melphalan followed by double umbilical cord blood transplantation (UCBT) with two partially HLA-matched units.

Secondary

• Determine the incidence of transplant-related mortality (TRM) at 6 months after UCBT.
• Determine the pharmacokinetics of mycophenolate mofetil and fludarabine phosphate in infants.
• Evaluate the pattern of chimerism after double UCBT.
• Determine the incidence of platelet engraftment at 1 year after UCBT.
• Determine the incidence of acute graft-versus-host disease (GVHD) grade II-IV and grade III-IV at day 100 after UCBT.
• Determine the incidence of chronic GVHD at 1 year after UCBT.
• Determine the overall survival and disease-free survival at 1 and 2 years after UCBT.
• Determine the incidence of relapse at 1 and 2 years after UCBT.
• Evaluate the developmental outcome after UCBT.

OUTLINE: This is an open-label, nonrandomized study.

• Non-irradiation containing myeloablative conditioning regimen: Patients receive busulfan IV over 2 hours 4 times daily on days -8 to -5 and fludarabine phosphate IV over 1 hour and melphalan IV over 30 minutes once daily on days -4 to -2.
• Double umbilical cord blood transplantation (UCBT): Patients undergo double UCBT IV over 15-30 minutes on day 0. Beginning on day 1, patients receive filgrastim (G-CSF) IV once daily until blood counts recover.
• Graft-vs-host disease prophylaxis: Patients receive cyclosporine IV over 2 hours 3 times daily and then orally twice daily beginning on day -3 and continuing until day 100 followed by a taper until day 180. Patients also receive mycophenolate mofetil IV and then orally 3 times daily beginning on day -3 and continuing until day 30 or 7 days after engraftment.

After completion of study treatment, patients are followed periodically for at least 5 years.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

• Leukemia
• Myelodysplastic Syndromes

• Biological: filgrastim
• Drug: busulfan
• Drug: cyclosporine
• Drug: fludarabine phosphate
• Drug: melphalan
• Drug: mycophenolate mofetil
• Procedure: allogeneic hematopoietic stem cell transplantation
• Procedure: umbilical cord blood transplantation

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following hematological malignancies:

  • Acute myeloid leukemia in complete remission (CR) or early relapse (i.e., < 15% blasts in bone marrow) and meets 1 of the following criteria:

    • In first CR (CR1) with high-risk disease as evidenced by the following:

      • High-risk cytogenetics

        • t(4;11) or other MLL rearrangements
        • Chromosome 5, 7, or 19 abnormalities
        • Complex karyotype (> 5 distinct changes)
      • Required ≥ 2 courses to achieve CR
    • In second or subsequent CR
    • AML evolved from prior myelodysplastic syndromes (MDS)

  • Acute lymphoblastic leukemia in CR, as defined by hematological recovery AND < 5% blasts by light microscopy within the bone marrow with a cellularity of ≥ 15%, and meets 1 of the following criteria:

    • In CR1 with high-risk disease as evidenced by the following:

      • High-risk cytogenetics

        • t(4;11) or other MLL rearrangements
        • t(9;22)
        • Hypodiploid
      • Required > 1 course to achieve CR
    • In second or subsequent CR

  • MDS with < 10% blasts by a representative bone marrow aspirate morphology and meets 1 of the following criteria:

    • International Prognostic Scoring System (IPSS) score of Int-2
    • IPSS score of high risk (i.e., refractory anemia with excess blasts [RAEB], RAEB in transformation [RAEBt])
    • Refractory anemia with severe pancytopenia or high risk cytogenetics
• No evidence of active extramedullary disease, including CNS leukemia
• No trisomy 21

• 4-6/6 HLA-A, -B, -DRB1 matched unrelated donor available

  • HLA-A and -B matched to antigen level resolution
  • HLA-DR matched to allele level resolution

  • Patients receive two partially HLA-matched units, if available

    • Double units must also be ≥ 4/6 match to each other
  • No existing HLA-identical, related donor available

PATIENT CHARACTERISTICS:

• Lansky play score 50-100%
• Glomerular filtration rate > 60mL/min
• Bilirubin ≤ 5 times upper limit of normal (ULN)
• AST/ALT ≤ 5 times ULN
• Alkaline phosphatase ≤ 5 times ULN
• Oxygen saturation > 92%
• LVEF ≥ 45%
• No active infection at time of transplantation, including Aspergillus or other mold within the past 30 days
• No history of HIV infection

PRIOR CONCURRENT THERAPY:

• More than 6 months since prior myeloablative transplantation