Donor Umbilical Cord Blood Transplant in Treating Patients With Advanced Hematological Cancer or Other Disease

RATIONALE: Giving low doses of chemotherapy and total-body irradiation before a donor umbilical cord blood transplant helps stop the growth of cancer or abnormal cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells 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 before and after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well donor umbilical cord blood transplant with reduced intensity conditioning works in treating patients with advanced hematological cancer or other disease.

OBJECTIVES:

Primary

* To estimate the probability of survival at 1 year in patients with advanced hematological malignancies or other diseases treated with non-myeloablative unrelated donor umbilical cord blood transplantation.

Secondary

* Six month non-relapse mortality.
* Chimerism at days 7, 14, 21, 28, 56, and 80, at 6 months, and at 1 and 2 years.
* To determine the incidence of neutrophil engraftment at day 42.
* To determine the incidence of platelet engraftment at 6 months.
* To determine the incidence of grade II-IV and III-IV acute graft-versus-host-disease (GVHD) at day 100.
* To determine the incidence of chronic GVHD at 1 year.
* To determine the incidence of clinically significant infections at 6 months and at 1 and 2 years.
* To determine the probability of progression-free survival at 1 and 2 years.
* To determine the probability of survival at 2 years.
* To determine the incidence of relapse or disease progression at 1 and 2 years.

OUTLINE: Patients are stratified according to disease status and prior therapy (hematologic malignancy or other disease that was treated with an autologous stem cell transplant or ≥ 2 courses of multiagent chemotherapy within the past 3 months vs hematologic malignancy or other disease that was treated with an autologous stem cell transplant \> 12 months ago or with ≤ 1 course of multiagent chemotherapy or immunosuppressive chemotherapy within the past 3 months vs refractory leukemia or lymphoma for which patient was rendered aplastic either by induction chemotherapy or radioimmunoconjugated monoclonal antibody therapy).

* Conditioning regimen: Patients receive fludarabine phosphate IV over 1 hour on days -6 to -2 and cyclophosphamide IV on day -6. Patients also undergo total body irradiation on day -1. Some patients also receive anti-thymocyte globulin IV on days -6 to -4.
* Umbilical cord blood transplantation (UCBT): Patients undergo UCBT on day 0.
* Immunosuppressive therapy (graft-versus-host disease prophylaxis): Patients receive cyclosporine IV over 1 hour or orally (as tolerated) every 8 or 12 hours beginning on day -3 and continuing for approximately 6 months. Patients also receive mycophenolate mofetil IV every 8 hours on days -3 to 5 and then orally on days 6-30.

After completion of study treatment, patients are followed at 6 months and then annually thereafter.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Diagnosis of advanced hematologic malignancy or other disease not curable by conventional chemotherapy, including any of the following:

  * Acute myeloid leukemia in complete remission (CR)\* (as defined by hematologic recovery, \< 5% blasts in the bone marrow by morphology, and a cellularity of \> 15%), meeting one of the following criteria:

    * In first complete remission (CR1) AND has high-risk disease as evidenced by any of the following:

      * Preceding myelodysplastic syndromes (MDS)
      * High-risk cytogenetics (e.g., monosomy 5 or 7, or as defined by referring institution treatment protocol)
      * Required \> 2 courses of therapy to obtain CR
      * Erythroblastic or megakaryocytic leukemia
    * In second CR (CR2) or beyond
  * Acute lymphoblastic leukemia in CR\* (as defined by hematologic recovery, \< 5% blasts in the bone marrow by morphology, and a cellularity of \> 15%), meeting one of the following criteria:

    * In CR1 AND has high-risk disease as evidenced by any of the following:

      * t(9;22), t(1;19), t(4;11), or other MLL rearrangements
      * Hyplodiploid
      * Required \> 1 course of therapy to obtain CR
    * Beyond CR2
  * Chronic myelogenous leukemia (CML)

    * All types are allowed (except refractory blast crisis CML)
    * Patients in chronic phase CML must have failed or been intolerant to prior imatinib mesylate (Gleevec) or other tyrosine kinase inhibitors
  * MDS

    * Any subtype allowed (including refractory anemia \[RA\])
    * Severe pancytopenia or complex cytogenetics
    * Blasts must be \< 5% (if blasts are ≥ 5%, pre-transplant induction therapy is required to reduce blast count to \< 5%)
  * Large cell lymphoma, Hodgkin lymphoma, or multiple myeloma, meeting one of the following criteria:

    * Chemotherapy-sensitive disease that has failed prior therapy

      * Patients with large cell lymphoma or Hodgkin lymphoma must not have progressive disease during salvage therapy (stable disease allowed provided it is non-bulky)
    * Ineligible for an autologous stem cell transplant
  * Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma, or follicular lymphoma that has progressed after ≥ 2 prior therapies

    * Patients with bulky disease should be considered for debulking chemotherapy prior to transplant
    * Patients with refractory disease are eligible provided disease is non-bulky AND an estimated tumor doubling time is ≥ 1 month
  * Lymphoplasmacytic lymphoma, mantle cell lymphoma, or prolymphocytic leukemia

    * Chemotherapy-sensitive disease that was previously treated with initial therapy

      * Patients with mantle cell lymphoma must not have progressive disease during salvage therapy (stable disease allowed provided it is non-bulky)
  * Mycosis fungoides and Sezary syndrome
  * Bone marrow failure syndromes, except for Fanconi anemia
  * Myeloproliferative syndromes NOTE: \*Patients for whom adequate marrow/biopsy specimens can not be obtained to determine remission status by morphologic assessment must have fulfilled criteria of remission (\< 5% blasts by flow cytometry and recovery of peripheral blood counts with no circulating blasts)
* Ineligible for autologous stem cell transplant due to any of the following:

  * Prior autologous stem cell transplant
  * Inadequate autologous stem cell harvest
  * Inability to withstand a myeloablative preparative regimen
  * Clinically aggressive/high-risk disease
* No evidence of progressive disease by imaging modalities or biopsy (persistent PET scan activity allowed provided there are no CT scan changes indicating progression)
* Acute leukemia that is refractory, persistent, or relapsed (defined as \> 5% blasts in normocellular bone marrow) allowed provided patient was rendered aplastic either by induction chemotherapy or radioimmunoconjugated monoclonal antibody therapy
* Patients with stable disease are eligible provided the largest residual nodal mass is approximately \< 5 cm (largest residual mass must represent a 50% reduction and be approximately \< 7.5 cm for patients who have responded to prior therapy)
* No active CNS malignancy
* Umbilical cord blood (UCB) donor available

  * UCB graft matched at 4/6 HLA-A, -B, and -DRB1 antigens with the recipient

    * May include 0-2 antigen mismatches at the A, B, or DRB1 loci
    * Unit selection based on cryopreserved nucleated cell dose and HLA-A, -B, and -DRB1 using intermediate resolution A, B antigen and DRB1 allele typing
  * If 2 UCB units are required to reach the target cell dose, each unit must be a 3/6 HLA-A, -B, and -DRB1 antigen match to each other, as well as a 4/6 antigen match to the recipient
  * No 5-6/6 HLA-A, -B, and -DRB1 matched sibling donor available

PATIENT CHARACTERISTICS:

* Karnofsky performance status (PS) 60-100% OR Lansky PS 50-100%
* Creatinine ≤ 2.0 mg/dL (adults) OR creatinine clearance \> 40 mL/min (pediatrics)

  * Adult patients with a creatinine \> 1.2 mg/dL or a history of renal dysfunction must have an estimated creatinine clearance of \> 40 mL/min
* Not pregnant or nursing
* Negative pregnancy test
* LVEF ≥ 35%
* DLCO \> 30% predicted
* No requirement for O_2
* No decompensated congestive heart failure
* No uncontrolled arrhythmia
* None of the following liver diseases or conditions:

  * Fulminant liver failure
  * Cirrhosis with evidence of portal hypertension or bridging fibrosis
  * Alcoholic hepatitis
  * Esophageal varices
  * History of bleeding esophageal varices, hepatic encephalopathy, or correctable hepatic synthetic dysfunction as evidenced by prolongation of the prothrombin time
  * Ascites related to portal hypertension
  * Bacterial or fungal abscess
  * Biliary obstruction
  * Chronic viral hepatitis with total serum bilirubin \> 3 mg/dL
  * Symptomatic biliary disease
* Recent mold infection (e.g., Aspergillus) allowed provided patient received ≥ 30 days of appropriate treatment AND infection is controlled and cleared by Infectious Disease
* No evidence of HIV infection or known HIV-positive serology
* No uncontrolled viral or bacterial infection

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* At least 3 months since prior myeloablative stem cell transplantation