RATIONALE: Giving chemotherapy, such as clofarabine, melphalan, and thiotepa, before a donor stem cell transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's 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 also make an immune response against the body's normal cells. Giving tacrolimus and mycophenolate mofetil before the transplant may stop this from happening.

PURPOSE: This phase I/II trial is studying the side effects and best dose of clofarabine when given together with melphalan and thiotepa, followed by a donor stem cell transplant and to see how well it works in treating patients with high-risk and/or advanced hematologic cancer or other disease.

OBJECTIVES:

Primary

• Determine the maximum tolerated dose of clofarabine when administered with melphalan and thiotepa followed by allogeneic stem cell transplantation in patients with high-risk and/or advanced hematologic malignancies. (Phase I)
• Determine the 1-year disease-free survival of patients treated with this regimen. (Phase II)
• Determine the efficacy of this regimen, in terms of antileukemic potential and relapse rate, in these patients.

Secondary

• Evaluate the incidence and severity of nonhematologic toxicity of this regimen in these patients.
• Evaluate the incidence and severity of graft-versus-host disease in patients treated with this regimen.

OUTLINE: This is a phase I, dose-escalation study of clofarabine followed by an open-label, phase II study. Patients are stratified according to HLA-compatible donor type (related vs unrelated).

• Cytoreductive therapy: Patients receive clofarabine IV over 2 hours once daily on days -9 to -5, thiotepa IV over 4 hours on day -4, and melphalan IV over 30 minutes once daily on days -3 and -2.

Cohorts of 3-6 patients receive escalating doses of clofarabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

• Graft-versus-host disease (GVHD) prophylaxis: Patients who undergo bone marrow or peripheral blood stem cell transplantation receive tacrolimus IV continuously over 24 hours or orally every 8-12 hours beginning on day -3 and methotrexate IV on days 1, 3, 6, and 11. Patients who undergo UCB transplantation receive tacrolimus IV continuously over 24 hours or orally every 8-12 hours beginning on day -3 and mycophenolate mofetil (MMF) IV or orally 2 or 3 times daily on days -3 to 45 followed by a taper until day 100 (unless there are signs of acute GVHD). Patients who undergo UCB transplantation without GVHD continue tacrolimus for 6 months followed by a taper and discontinued 1 year after transplantation.
• Allogeneic hematopoietic stem cell transplantation (HSCT) or allogeneic umbilical cord blood (UCB) transplantation: Patients undergo allogeneic HSCT (bone marrow or peripheral blood stem cells) or double UCB transplantation on day 0. Patients also receive filgrastim (G-CSF) IV or subcutaneously beginning on day 7 and continuing until blood counts recover.
• Maintenance therapy: Approximately 2 months after transplantation patients with ALL, M4 or M5 AML, and those transplanted with AML in bone marrow relapse receive cytarabine intrathecally (IT) monthly for up to 5 doses. Patients with a history of CNS leukemia receive cytarabine IT once monthly during months 2-12 after HSCT.

After completion of study therapy, patients are followed periodically for at least 4 years.

PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed diagnosis of 1 of the following:

  • Acute myelogenous leukemia, meeting 1 of the following criteria:

    • In first complete remission (CR), meeting 1 of the following criteria:

      • Poor risk [no t(15,17), inv 16, or t(8,21)]
      • Not a candidate for total body irradiation (TBI)
      • Any infant in first CR

    • In second CR, meeting the following criteria:

      • All patients

    • In more than second CR OR relapsed/refractory disease, meeting the following criteria:

      • All patients
      • Blast percentage > 5% and < 25% in bone marrow (BM) at the time of stem cell transplantation (SCT)

  • Acute lymphoblastic leukemia, meeting 1 of the following criteria:

    • In first CR, meeting 1 of the following criteria:

      • Poor risk [t(9;22), t(4;11) AND no CR after 7-28 days of induction]
      • Not a candidate for TBI
      • Any infant in first CR

    • In second CR, meeting the following criteria:

      • All patients

    • In more than second CR OR relapsed/refractory disease, meeting the following criteria:

      • All patients
      • Blast percentage > 5% and < 25% in BM at the time of SCT

    • Acute undifferentiated or biphenotypic leukemia, meeting the following criteria:

      • All patients
      • Blast percentage > 5% and < 25% in BM at the time of SCT

    • Chronic myelogenous leukemia, meeting the following criteria:

      • All patients
      • In first chronic phase

    • Myelodysplastic syndrome, meeting 1 of the following criteria:

      • Primary high risk disease

        • Stage > RAEB1

      • Secondary high risk disease

        • All patients
        • Any stage

      • Juvenile myelomonocytic leukemia

        • All patients

• No doubling of peripheral blast counts within a period of 2 weeks

• No active CNS disease

• HLA-compatible donor available meeting 1 of the following criteria:

  • Related donor

    • Genotypically or phenotypically matched at ≥ 7 or 8 of HLA-A, -B, -C and -DRB1 alleles

  • Unrelated donor meeting 1 of the following criteria:

    • 8 of 8 alleles matched
    • For patients < 18 years old only: 7 or 8 alleles matched with the mismatch at only 1 HLA-A, -B, -C, or -DRB1 allele

• Two HLA-compatible unrelated cord blood (UCB) units available meeting the following criteria:

  • HLA-matched minimally at 4 of 6 HLA-A, HLA-B, and DRB1 allele

    • HLA-A and HLA-B matched at intermediate resolution by molecular technique
    • DRB1 allele matched at high resolution by molecular technique

  • Both matched UCB units with cryopreserved nucleated cell dose ≥ 1.5 x 10^7/kg

PATIENT CHARACTERISTICS:

• Karnofsky OR Lansky performance status 70-100%
• SGOT < 2 times upper limit of normal
• Bilirubin < 1.5 mg/dL (unless there is liver disease involvement)
• Creatinine normal OR creatinine clearance > 60 mL/min
• LVEF > 50% at rest OR shortening fraction ≥ 29%
• Patients with asymptomatic pulmonary disease with no prior risk factors OR symptomatic pulmonary disease with diffusion capacity > 50% of predicted (corrected for hemoglobin) are eligible
• No active uncontrolled viral, bacterial, or fungal infection
• No known HIV I or II positivity
• No known human T-cell lymphotrophic virus I or II positivity
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• No hydroxyurea within the past 2 weeks
• No allogeneic or autologous stem cell transplantation within the past 6 months