Inclusion Criteria:

• Age, Performance Status, and Graft Criteria
  • <70 years of age with no matched 5/6 or 6/6 sibling donor - patients ≥ 70 and ≤ 75 years of age may be eligible if they have a Co-Morbidity score ≤ 2 - refer to appendix II
  • Karnofsky score ≥ 70% (≥ 16 years) or Lansky score ≥ 50 (< 16 years)
  • UCB graft selected according to current University of Minnesota umbilical cord blood graft selection algorithm
• Eligible Diseases All diseases listed below are advanced hematologic malignancies not curable by conventional chemotherapy. Responses to conventional treatment range from zero to 30% but are typically short lived.
  • Acute Leukemias: Must be in remission by morphology (<5% blasts). Note cytogenetic relapse or persistent disease without morphologic relapse is acceptable. Also a small percentage of blasts that is equivocal between marrow regeneration vs. early relapse are acceptable provided there are no associated cytogenetic markers consistent with relapse.
    • Acute myeloid leukemia: high risk CR1 (as evidenced by preceding MDS, high risk cytogenetics such as those associated with MDS or complex karyotype, > 2 cycles to obtain CR or erythroblastic or megakaryocytic leukemia, FLT-3 ITD +); second or greater CR.
    • Acute lymphoblastic leukemia/lymphoma: high risk CR1 as evidenced by high risk cytogenetics (e.g. t(9;22), t(1;19),t(4;11), other MLL rearrangements, hypodiploidy or IKZF1), > 1 cycle to obtain CR or evidence of minimal residual disease (MRD). Patients in second or greater CR are also eligible.
  • Burkitt's lymphoma in CR2 or subsequent CR
  • Natural killer cell malignancies
  • Chronic myelogenous leukemia: all types except refractory blast crisis. Chronic phase patients must have failed or been intolerant to at least two tyrosine kinase inhibitors.
  • Myelodysplastic syndrome requiring transplant as defined as: IPSS INT-2 or High Risk; R-IPSS High or Very High; WHO classification: RAEB-1, RAEB-2; Severe Cytopenias: ANC < 0.8, PRBC or platelets requiring transfusion; Higher risk cytogenetics based on IPSS or R-IPSS definitions; therapy-related MDS. Blasts must be < 5% by a representative bone marrow aspirate morphology.
  • Large-cell lymphoma, Hodgkin lymphoma and multiple myeloma with chemotherapy sensitive disease who are ineligible for an autologous transplant.
  • Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma, follicular lymphoma that have progressed within 12 months of achieving a partial or complete remission. Patients who had remissions lasting > 12 months, are eligible after at least two prior therapies. Patients with bulky disease should be considered for debulking chemotherapy before transplant. Patients with refractory disease are eligible, unless has bulky disease and an estimated tumor doubling time of less than one month.
  • Lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia are eligible after initial therapy if chemotherapy sensitive.
  • Bone marrow failure syndromes, except for Fanconi anemia
  • Myeloproliferative syndromes
• Additional Criteria for Bulky Disease (lymphomas)
  • If stable disease is best response, the largest residual nodal mass must < 5 cm (approximately)
  • If response to previous therapy, the largest residual mass must represent a 50% reduction and be < 7.5 cm (approximately)
• Organ Function Criteria

Adequate organ function is defined as:

• Cardiac: Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction > 35%.
• Pulmonary: DLCOcorr ≥ 40% predicted, and absence of O2 requirements. For children that are not able to cooperate with PFTs, a pulse oximetry with or without exercise should be attempted. If neither test can be obtained it should be clearly stated in the physician's note.
• Liver: AST and ALT < 5 x upper limit of normal and bilirubin < 3 x upper limit of normal
• Renal: Creatinine ≤ 2.0 mg/dl (adults) and estimated glomerular filtration rate (GFR) ≥ 40 mL/min (pediatrics). Adults with a creatinine > 1.2 mg/dl or a history of renal dysfunction must have estimated glomerular filtration rate (GFR) > 40 mL/min.
  • Women of childbearing potential and males with partners of child-bearing potential must agree to use adequate birth control during study treatment.
  • Voluntary written consent (adult or parent/guardian with presentation of the minor information sheet, if appropriate)

Exclusion Criteria:

• Pregnant or breast feeding. The agents used in this study include Pregnancy Category D: known to cause harm to a fetus. Females of childbearing potential must have a negative pregnancy test prior to starting therapy.
• Untreated active infection
• Active HIV infection or known HIV positive serology
• Less than 3 months since prior myeloablative transplant (if applicable)
• Evidence of progressive disease by imaging modalities or biopsy - persistent PET activity, though possibly related to lymphoma, is not an exclusion criterion in the absence of CT changes indicating progression.
• CML in blast crisis
• Large cell lymphoma, mantle cell lymphoma and Hodgkin disease that is progressing on salvage therapy.
• Active central nervous system malignancy