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

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