Fludarabine, Cyclophosphamide, and Total-Body Irradiation Followed by Cyclosporine and Mycophenolate Mofetil in Treating Patients Who Are Undergoing a Donor Umbilical Cord Blood Transplant for Hematologic Cancer

RATIONALE: Giving low doses of chemotherapy, such as fludarabine and cyclophosphamide, 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 transplant may stop this from happening.

PURPOSE: This clinical trial is studying how well giving fludarabine and cyclophosphamide together with total-body irradiation followed by cyclosporine and mycophenolate mofetil works in treating patients who are undergoing a donor umbilical cord blood transplant for hematologic cancer.

OBJECTIVES:

* Determine the frequency, extent, and rate of donor (myeloid and lymphoid) engraftment in patients with serious hematologic malignancies treated with nonmyeloablative conditioning regimen comprising fludarabine, cyclophosphamide, and low-dose total-body irradiation followed by unrelated allogeneic umbilical cord blood transplantation and post-transplant immunosuppression comprising cyclosporine and mycophenolate mofetil.
* Correlate clinical and umbilical cord blood-related factors with engraftment in patients treated with this regimen.
* Determine transplant-related complications, in terms of toxicity, myelosuppression, infections, and acute and chronic graft-versus-host disease, in patients treated with this regimen.
* Determine disease-free and overall survival of patients treated with this regimen.
* Determine treatment-related mortality of patients treated with this regimen.

OUTLINE: This is a uncontrolled, pilot study.

* Nonmyeloablative conditioning regimen: Patients receive fludarabine IV over 30 minutes daily on days -6 to -2 and cyclophosphamide IV over 2 hours on day -6 and undergo low-dose total-body irradiation (TBI) on day 0.
* Unrelated allogeneic umbilical cord blood transplantation (UCBT): After completion of TBI, patients undergo 1 or 2 unrelated allogeneic UCBTs on day 0.
* Post-transplant immunosuppression: Patients receive oral or IV cyclosporine daily beginning on day -3 and continuing until day 180 and oral or IV mycophenolate mofetil twice daily on days 0-30.

Patients are followed periodically for 1 year after transplantation.

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

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Diagnosis of 1 of the following hematologic malignancies:

  * Acute myeloid leukemia (AML) with or without history of myelodysplastic syndromes, meeting 1 of the following criteria:

    * In first complete remission (CR-1) with unfavorable cytogenetics and/or achieved CR-1 after ≥ 1 course of induction therapy
    * Secondary or treatment-related AML
    * In second or further complete remission
    * Relapsed with ≤ 20% blasts in the bone marrow AND no circulating blasts
  * Acute lymphoblastic leukemia (ALL), meeting 1 of the following criteria:

    * In CR-1 with unfavorable cytogenetics or elevated WBC at presentation OR failed to achieve CR-1 after ≥ 4 weeks of induction therapy
    * In second or further complete remission
    * Relapsed with ≤ 20% blasts in the bone marrow AND no circulating blasts
  * Other acute leukemic variants allowed at the discretion of the principal investigator
  * Chronic myelogenous leukemia (CML), meeting 1 of the following criteria:

    * In first chronic phase AND refractory to or unable to tolerate imatinib mesylate
    * In second or further chronic phase
    * In first or second accelerated phase
  * Myelodysplastic syndromes with intermediate 2- or high-risk International Prognosis Scoring System (IPSS) score, including any of the following:

    * Refractory anemia
    * Refractory anemia with excess blasts
    * Chronic myelomonocytic leukemia
  * Myeloproliferative disorders with poor prognosis, including any of the following:

    * Myelofibrosis with myeloid metaplasia

      * No ≥ grade 3 myelofibrosis
    * Atypical CML
    * Juvenile myelomonocytic leukemia
  * Other clonal hemopathies with an accepted poor prognosis
  * Multiple myeloma with chromosome 13 abnormalities and/or progression after prior autologous bone marrow transplantation (BMT)
  * Chronic lymphocytic leukemia, meeting 1 of the following criteria:

    * Primary refractory OR relapsed and refractory disease (less than partial remission)
    * Relapsed twice on or after prior chemotherapy
  * Lymphoma, meeting both of the following criteria:

    * Hodgkin's or non-Hodgkin's lymphoma in \> CR-1 OR failed primary induction
    * Chemosensitive disease, defined as \> 50% reduction in mass size after the most recent chemotherapy
* Must meet ≥ 1 of the following criteria:

  * Over 45 years of age
  * Has undergone prior autologous or allogeneic BMT
  * Charlson\^ comorbidity score ≥ 2
* Must have a high degree of tumor control (salvage therapy allowed)
* At high risk for treatment-related mortality with a myeloablative conditioning regimen
* No massive splenomegaly

  * Patients may become eligible after splenectomy or radiotherapy to the spleen
* No 5/6 or 6/6 HLA-matched related donor available
* No well-matched (i.e., ≥ 9/10 HLA match by high-resolution typing) unrelated donor available

PATIENT CHARACTERISTICS:

Performance status

* Not specified

Life expectancy

* Not specified

Hematopoietic

* See Disease Characteristics

Hepatic

* Bilirubin ≤ 2 times upper limit of normal (ULN)
* Transaminases ≤ 4 times ULN (unless due to underlying disease)

Renal

* Creatinine clearance ≥ 50 mL/min

Cardiovascular

* Ejection fraction ≥ 30%

Pulmonary

* DCLO ≥ 35%

Other

* Negative pregnancy test
* No uncontrolled viral, bacterial, or fungal infection
* HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

* See Disease Characteristics

Chemotherapy

* See Disease Characteristics

Radiotherapy

* See Disease Characteristics

Other

* At least 3 months since prior immunosuppressive therapy
* At least 10 days since prior salvage therapy for patients not in at least morphologic or radiologic complete remission