• Transplant-related mortality at 6 months after umbilical cord blood transplantation (UCBT) [ Designated as safety issue: No ]
• Chimerism [ Designated as safety issue: No ]

• Transplant-related mortality at 6 months after umbilical cord blood transplantation (UCBT)
• Chimerism

RATIONALE: Giving chemotherapy drugs, such as fludarabine and cyclophosphamide, and total-body irradiation before a donor umbilical cord blood stem cell transplant helps stop the growth of 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 giving fludarabine and cyclophosphamide together with total-body irradiation works in treating patients who are undergoing an umbilical cord blood transplant for hematologic cancer.

OBJECTIVES:

Primary

• Determine the 1-year survival of patients undergoing unrelated umbilical cord blood transplantation (UCBT) for hematologic malignancies treated with myeloablative preparative regimen comprising fludarabine, cyclophosphamide, and fractionated total-body irradiation.

Secondary

• Determine the incidence of transplant-related mortality at 6 months after UCBT.
• Evaluate the pattern of chimerism after double UCBT.
• Determine the incidence of neutrophil engraftment at day 42 after UCBT.
• Determine the incidence of platelet engraftment at 1 year after UCBT.
• Determine the incidence of grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) at day 100 after UCBT.
• Determine the incidence of chronic GVHD at 1 year after UCBT.
• Determine the disease-free survival at 1 and 2 years after UCBT.
• Determine the incidence of relapse at 1 and 2 years after UCBT.

OUTLINE: This is a nonrandomized, open-label, multicenter study.

• Preparative Regimen: Patients receive fludarabine IV over 1 hour on days -8 to -6 and cyclophosphamide IV on days -7 and -6. Patients also undergo total-body irradiation twice daily on days -4 to -1.
• Umbilical Cord Blood Transplantation (UCBT): Patients undergo 1 or 2 units of UCBT on day 0. Patients receive filgrastim (G-CSF) IV once daily beginning on day 1 and continuing until blood counts recover.
• Graft-versus-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV over 2 hours 2 or 3 times daily beginning on day -3 and continuing until day 100 followed by a taper until day 180. Patients also receive mycophenolate mofetil IV or orally 2 or 3 times a day beginning on day -3 and continuing until day 30 or 7 days after engraftment in the absence of acute GVHD.

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

PROJECTED ACCRUAL: A total of 150 patients will be accrued for this study.

• Chronic Myeloproliferative Disorders
• Leukemia
• Lymphoma
• Multiple Myeloma and Plasma Cell Neoplasm
• Myelodysplastic Syndromes

• Biological: filgrastim
• Drug: cyclophosphamide
• Drug: cyclosporine
• Drug: fludarabine phosphate
• Drug: mycophenolate mofetil
• Procedure: umbilical cord blood transplantation
• Radiation: total-body irradiation

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following hematologic malignancies:

  • Acute myeloid leukemia (AML)

    • Disease in second or subsequent complete remission (CR)* OR in first CR* with high-risk features, as defined by 1 of the following:

      • Preceding myelodysplastic syndromes (MDS)
      • High-risk cytogenetics
      • Two or more courses of therapy required to obtain CR*
      • Erythroblastic or megakaryocytic leukemia
    • Very high-risk pediatric patients (< 21 years of age) are eligible provided M2 marrow ≤ 25% blasts after failing ≥ 1 course of prior chemotherapy

  • Acute lymphocytic leukemia (ALL)

    • Disease in second or subsequent CR* OR in first CR* with high-risk features, as defined by 1 of the following:

      • High-risk cytogenetics [t(9;22), t(1;19), t(4;11), or other MLL rearrangements]
      • More than 1 course of therapy required to obtain CR*

  • Chronic myelogenous leukemia

    • Not in refractory blast crisis
    • Must have failed or be intolerant to imatinib mesylate (for patients in first chronic phase)
  • Advanced myelofibrosis

  • MDS

    • Refractory anemia with severe pancytopenia or high-risk cytogenetics OR intermediate-2- or high-risk MDS by International Prognostic

Scoring System, including any of the following:

• Refractory anemia with excess blasts (RAEB)

• RAEB in transformation

  • Blasts < 10% by a representative bone marrow aspirate morphology

    • Chronic lymphocytic leukemia
  • Disease progressed after ≥ 2 prior therapies

  • Patients with bulky disease (nodal mass > 5cm) may undergo debulking chemotherapy before transplantation

    • Prolymphocytic leukemia

  • Disease in first or subsequent CR or partial remission (PR) after initial therapy

    • Multiple myeloma, meeting 1 of the following criteria:
  • Beyond second PR
  • Completed initial therapy AND meets 1 of the following criteria:
• Chromosome 13 abnormalities
• First response lasted < 6 months

• Beta-2 microglobulin > 3 mg/L

  • Any of the following non-Hodgkin's lymphoma (NHL)

    • Patients with small lymphocytic lymphoma, marginal zone B-Cell lymphoma, or follicular lymphoma must have disease progression after ≥ 2 prior therapies

• Patients with bulky disease (nodal mass > 5cm) may undergo debulking chemotherapy before transplantation

  • Patients with lymphoplasmacytic lymphoma or mantle cell lymphoma must have undergone initial therapy and be in first or subsequent CR or PR
  • Patients with large cell NHL must meet both of the following criteria:
• In second CR or PR with initial short remission (< 6 months) OR beyond second CR or PR

• Not refractory to chemotherapy (i.e., progressive disease after > 2 salvage regimens)

  • Patients with lymphoblastic lymphoma, Burkitt's lymphoma, or other high-grade NHL must meet the following criteria:
• Disease progressed within 1 year after initial therapy (for patients with stage I or II disease)
• Competed initial therapy AND disease in first CR or PR (for patients with stage III or IV disease)

• Not refractory to chemotherapy (i.e., progressive disease after > 2 salvage regimens) NOTE: *CR is defined by hematologic recovery AND marrow < 5% blasts by light microscopy with ≥ 15% cellularity (for patients with AML or ALL)

  • Must have HLA matched unrelated umbilical cord blood (UCB) donor available

    • Must be 4/6, 5/6, or 6/6 HLA-A, -B, and -DRB1 matched

    • May use 1 or 2 units of UCB

      • If using 2 units, each unit must be 4/6 HLA-A, -B, and -DRB1 matched to both the patient and the other unit
  • No HLA-identical related donor available NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma.

However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

• Karnofsky performance status (PS) 80-100% (for adult patients) OR Lansky PS 50-100% (for pediatric patients)
• Creatinine ≤ 2.0 mg/dL (for adult patients) OR creatinine clearance > 40 mL/min (for pediatric patients)
• AST and ALT ≤ 2 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 2 times ULN
• Bilirubin ≤ 2 times ULN
• DLCO_corr > 50% of normal
• LVEF ≥ 45%
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No Aspergillus or other mold infection within the past 30 days
• No history of HIV infection
• No other active infection at the time of study transplantation

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior alkylator therapy lasting > 12 months (6 months for alkylator therapy with extensive radiotherapy)
• More than 6 months since prior myeloablative transplantation (for patients ≤ 18 years of age)
• No prior myeloablative allogeneic or autologous transplantation (for patients > 18 years of age)
• No other prior extensive therapy
• No prior salvage therapy with yttrium Y 90 ibritumomab tiuxetan or iodine I 131 tositumomab