This phase II trial is studying the safety and potential efficacy of infusing non-human leukocyte antigen matched ex vivo expanded cord blood progenitors with one or two unmanipulated umbilical cord blood units for transplantation following conditioning with fludarabine phosphate, cyclophosphamide and total body irradiation, and immunosuppression with cyclosporine and mycophenolate mofetil for patients with hematologic malignancies. Chemotherapy, such as fludarabine phosphate and cyclophosphamide, and total-body irradiation given before an umbilical cord blood transplant stops the growth of leukemia cells and works to prevent the patient's immune system from rejecting the donor's stem cells. The healthy stem cells from the donor's umbilical cord blood help the patient's bone marrow make new red blood cells, white blood cells, and platelets. It may take several weeks for these new blood cells to grow. During that period of time, patients are at increased risk for bleeding and infection. Faster recovery of white blood cells may decrease the number and severity of infections. Studies have shown that counts recover more quickly when more cord blood cells are given with the transplant. We have developed a way of growing or "expanding" the number of cord blood cells in the lab so that there are more cells available for transplant. We are doing this study to find out whether or not giving these expanded cells along with one or two unexpanded cord blood units is safe and if use of expanded cells can decrease the time it takes for white blood cells to recover after transplant. We will study the time it takes for blood counts to recover, which of the two or three cord blood units makes up the patient's new blood system, and how quickly immune system cells return.

PRIMARY OBJECTIVES:

I. Examine the safety and toxicity when ex vivo expanded cord blood cells are infused as an off-the-shelf non-human leukocyte antigen (HLA) matched product with the goal of providing rapid but transient myelopoiesis in the setting of a single or double umbilical cord blood transplant.

II. Examine the in vivo persistence of the ex vivo expanded cord blood product. The kinetics and durability of hematopoietic reconstitution will be determined and the relative contribution to engraftment of the expanded cord blood product and the unmanipulated cord blood unit(s) in early and long-term engraftment will be determined by frequent determination of donor chimerisms in the peripheral blood.

SECONDARY OBJECTIVES

I. Estimate the incidence and severity of acute and chronic graft-versus-host-disease (GVHD) in patients receiving off-the-shelf ex vivo expanded and cryopreserved cord blood cells.

II. Estimate the incidence of transplant related mortality at day 100.

III. Estimate the incidence of malignant relapse and probabilities of overall and event-free survival at 1 and 2 years post transplant.

IV. Obtain preliminary data on the incidence of infections/viral reactivation from the start of conditioning to 100 days post transplant and then at 6 months, 1 year and 2 years post transplant as possible.

V. Obtain preliminary data on the phenotype and function of immune cells recovering in patients receiving expanded and unmanipulated cord blood grafts.

VI. Examination of possible immunologic factors leading to emergence of a dominant unit.

OUTLINE:

MYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) over 1 hour on days -8 to -6 and cyclophosphamide IV on days -7 and -6. Patients undergo total-body irradiation (TBI) twice daily on days -4 to -1.

TRANSPLANTATION: Patients undergo unmanipulated single- or double-unit umbilical cord blood transplantation on day 0 and receive ex vivo-expanded cord blood progenitor cells IV over 4 hours following the last unmanipulated cord blood infusion.

GVHD PROPHYLAXIS: Patients initially receive cyclosporine (CSP) IV over 1 hour beginning on day -3. CSP may be given orally (PO) when the patient can tolerate oral medications and has a normal gastrointestinal transit time. CSP is given until day 100, and may taper on day 101 if there is no graft versus host disease. Patients also receive mycophenolate mofetil (MMF) IV every 8 hours on days 0 to 7 and then may receive MMF PO beginning day 8 to 30. MMF is continued for a minimum of 30 days or until 7 days after blood counts recover whichever is later. If there is no evidence of acute GVHD and donor cluster of differentiation (CD)3 engraftment is at least 50% from one donor MMF may be tapered.

Inclusion Criteria:

• Acute myeloid leukemia:

  • High risk complete response (CR)1 as evidenced by preceding myelodysplastic syndromes (MDS), high risk cytogenetics (for example, monosomy 5 or 7, or as defined by referring institution treatment protocol), >= 2 cycles to obtain CR, erythroblastic or megakaryocytic leukemia; >= CR2
  • All patients must be in CR as defined by hematologic recovery and < 5% blasts by morphology within the bone marrow and a cellularity of >= 15%
  • Patients in which adequate marrow/biopsy specimens cannot be obtained to determine remission status by morphologic assessment, but have fulfilled criteria of remission by flow cytometry, recovery of peripheral blood counts with no circulating blasts, and/or normal cytogenetics (if applicable) may still be eligible; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures; these patients must be discussed with the Principal Investigator, Colleen Delaney prior to enrollment

• Acute lymphoblastic leukemia:

  • High risk CR1 [for example, but not limited to: t(9;22), t(1;19), t(4;11) or other mixed lineage leukemia (MLL) rearrangements, hypodiploid]
  • Greater than 1 cycle to obtain CR
  • >= CR2
  • All patients must be in CR as defined by hematologic recovery and < 5% blasts by morphology within the bone marrow and a cellularity of >= 15%
  • Patients in which adequate marrow/biopsy specimens cannot be obtained to determine remission status by morphologic assessment, but have fulfilled criteria of remission by flow cytometry, recovery of peripheral blood counts with no circulating blasts, and/or normal cytogenetics (if applicable) may still be eligible; reasonable attempts must be made to obtain an adequate specimen for morphologic assessment, including possible repeat procedures; these patients must be discussed with the Principal Investigator, Colleen Delaney prior to enrollment

• Chronic myelogenous leukemia excluding refractory blast crisis; to be eligible in first chronic phase (CP1) patient must have failed or be intolerant to imatinib mesylate

• Myelodysplasia (MDS) International Prognostic Scoring System (IPSS) intermediate 2 (Int-2) or high risk (i.e., refractory anemia with excess myeloblasts [RAEB], refractory anemia with excess blasts in transformation [RAEB-T]) or refractory anemia with severe pancytopenia or high risk cytogenetics; blasts must be < 10% by a representative bone marrow aspirate morphology

• Karnofsky (>= 16 years old) >= 70%

• Lansky (< 16 years old) >= 50%

• Calculated creatinine clearance must be > 60 mL and serum creatinine =< 2 mg/dL (adults)

• Calculated creatinine clearance must be > 60 mL/min (children < 18 years old)

• Total serum bilirubin must be < 3 mg/dl

• Transaminases must be < 3 x the upper limit of normal

• Diffusion capacity of the lung for carbon monoxide (DLCO) corrected > 50% normal

• For pediatric patients unable to perform pulmonary function tests, oxygen (O2) saturation > 92% on room air

• Left ventricular ejection fraction > 45% OR shortening fraction > 26%

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Uncontrolled viral or bacterial infection at the time of study enrollment
• Active or recent (prior 6 month) invasive fungal infection without infectious disease (ID) consult and approval
• History of human immunodeficiency virus (HIV) infection
• Pregnant or breastfeeding
• If =< 18 years old, prior myeloablative transplant within the last 6 months
• If > 18 years old prior myeloablative allotransplant or autologous transplant
• Extensive prior therapy including > 12 months alkylator therapy or > 6 months alkylator therapy with extensive radiation