Chemotherapy and Total-Body Irradiation Followed by Donor Umbilical Cord Blood Transplant, Cyclosporine, and Mycophenolate Mofetil in Treating Patients With Hematologic Cancer

RATIONALE: Giving low doses of chemotherapy, such as cyclophosphamide and fludarabine, and radiation therapy before a donor umbilical cord blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.

PURPOSE: This clinical trial is studying how well giving chemotherapy together with total-body irradiation followed by donor umbilical cord blood transplant, cyclosporine, and mycophenolate mofetil works in treating patients with hematologic cancer.

OBJECTIVES:

Primary

* Determine the engraftment potential of unrelated allogeneic umbilical cord blood (UCB) using nonmyeloablative conditioning comprising fludarabine, cyclophosphamide, and total-body irradiation followed by post-transplant immunosuppression comprising cyclosporine and mycophenolate mofetil in patients with hematologic malignancies.

Secondary

* Determine the rate of neutrophil and platelet recovery and the completeness of donor cell engraftment in patients treated with this regimen.
* Determine the incidence and severity of acute and chronic graft-versus-host disease (GVHD) in patients treated with this regimen.
* Determine the incidence of malignant relapse in patients treated with this regimen.
* Determine the 1- and 2-year survival and event-free survival of patients treated with this regimen.
* Determine the phenotype and function of immune cells recovering after UCB transplantation in patients treated with this regimen.
* Determine the toxicity of this regimen in these patients.

OUTLINE: Patients are stratified according to HLA disparity (0-1 vs 2) and number of graft units (1 vs 2).

* Nonmyeloablative conditioning: Patients receive nonmyeloablative conditioning comprising fludarabine IV over 1 hour on days -8 to -6 and cyclophosphamide IV over 2 hours on days -7 and -6. Patients undergo total-body irradiation twice daily on days -4 to -1.
* Unrelated allogeneic umbilical cord blood transplantation (UCBT): Patients undergo 1 or 2 unrelated allogeneic UCBTs on day 0.
* Immunosuppression: Patients receive cyclosporine orally or IV over 2 hours 2-3 times daily beginning on day -3 and continuing until day 100, followed by a taper in the absence of graft-vs-host disease (GVHD). Patients also receive mycophenolate mofetil orally or IV twice daily on days -3 to 30, continuing beyond day 30 if no donor engraftment. Patients also receive filgrastim (G-CSF) IV or subcutaneously beginning on day 1 and continuing until blood counts recover.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Diagnosis of a hematologic malignancy of 1 of the following types:

  * Acute myeloid leukemia (AML), meeting the following criteria:

    * In complete remission (CR) by morphology (\< 5% blasts in the bone marrow), as defined by 1 of the following:

      * In first CR (CR1) and meets ≥ 1 of the following high-risk criteria:

        * High-risk cytogenetics (e.g., those associated with myelodysplastic syndromes \[MDS\] or complex karotype)
        * Preceding MDS
        * More than 2 courses of therapy was required to obtain CR
      * In second or greater CR
    * No morphologic relapse

      * Cytogenetic relapse or persistent disease allowed
  * Acute lymphocytic leukemia (ALL), meeting the following criteria:

    * In CR, as defined by 1 of the following:

      * In CR1 and meets ≥ 1 of the following high-risk criteria:

        * Unfavorable high-risk cytogenetics \[t(9;22), t(1;19), t(4;11) or other MLL rearrangements\]
        * More than 1 course of therapy was required to obtain CR
      * In second or greater CR
    * No morphologic relapse or persistent disease
  * Chronic myelogenous leukemia (CML), excluding refractory blast crisis
  * Advanced myelofibrosis
  * Advanced myelodysplasia (blasts \< 10% \[otherwise need AML induction pre-transplant\]), meeting ≥ 1 of the following criteria:

    * Refractory anemia with excess blasts (RAEB)
    * RAEB in transformation
    * Refractory anemia with severe pancytopenia
    * High-risk cytogenetics
  * Non-Hodgkin's lymphoma (NHL), meeting the following criteria:

    * One of the following histologic subtypes:

      * Mantle cell NHL

        * Disease progression after initial therapy (e.g., CHOP)
        * Beyond CR1 or beyond first partial remission (PR)
      * Intermediate-grade NHL in second or greater CR or PR
      * High-grade NHL

        * Stage III or IV disease AND received initial therapy
        * Stage I or II disease at diagnosis that subsequently progressed after a prior response duration of \< 1 year
    * No chemotherapy-refractory NHL (i.e., \< progressive disease after \> 2 salvage regimens)
* Donor available, meeting the following criteria:

  * No other existing HLA-identical related donor available
  * 4-6/6 HLA-A, -B, and -DRB1, matched unrelated donor by molecular techniques

    * A and B to antigen level resolution
    * DR to allele resolution
  * Umbilical cord blood (UCB) graft may consist of one or two UCB units 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 score 80-100% (for adults) OR
* Lansky score 50-100% (for children)
* Creatinine ≤ 2.0 mg/dL (for adults) OR creatinine clearance \> 40 mL/min (for children)

  * Adults with a creatinine \> 1.2 mg/dL or a history of renal dysfunction must have a creatinine clearance \> 40 mL/min
* Bilirubin ≤ 2 times normal
* AST and ALT ≤ 2 times normal
* Alkaline phosphatase ≤ 2 times normal
* Pulmonary function \> 50 % of normal
* LVEF ≥ 45%
* No active infection, including Aspergillus or other mold, within the past 30 days
* No history of HIV infection
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* No prior myeloablative transplant within the past 6 months if ≤ 18 years old
* No prior myeloablative allotransplant or autologous transplant if \> 18 years old
* No prior extensive therapy (e.g., \> 12 months of alkylating therapy or \> 6 months of alkylating therapy with extensive radiation)