A Myeloablative Conditioning Regimen and Total Body Irradiation Followed by the Transplantation for Patients With Hematological Malignancy

Inclusion Criteria

• Age 4 - 50 years
• Patient should not have a related or unrelated volunteer donor that is suitably HLA matched and available in the required time period or be a suitable candidate for an autologous stem cell transplant.
• Patients will have one of the following hematological malignancies: Acute myelogenous leukemia (AML):
• Complete first remission (CR1) at high risk for relapse as defined by:

known prior diagnosis of myelodysplasia (MDS); or therapy related AML; or White cell count at presentation > 100,000; or Presence of extramedullary leukemia at diagnosis; or Unfavorable FAB type (M0, M5-7); or High-risk cytogenetics (such as those associated with MDS, abnormalities of 5, 7, 8, Philadelphia chromosome, complex karyotype); or High risk molecular markers such as FLT3 mutations; or Requirement for 2 or more inductions to achieve CR1

• Complete second CR (CR2).
• Acute lymphoblastic leukemia (ALL):
• Complete first remission (CR1) at high risk for relapse as defined by:

White cell count at presentation as follows:

• > 100, 000 if 50,000 if > 18 years; or

Presence of extensive extra-medullary disease (excluding CNS disease); or Presence of high-risk cytogenetic abnormality such as t(9;22), t(1;19), t(4;11) or other MLL rearrangements (11q23), t(8;14) [excluding B-ALL in pediatric patients]; or

Failed to achieve complete remission after four weeks of induction therapy Unable to receive required consolidation chemotherapy as would be needed to maintain remission

• Complete second or third remission (CR2 or CR3)
• Acute undifferentiated leukemia (AUL), infant leukemia, or biphenotypic leukemia in CR1, CR2 or CR3. Patients with infant leukemia must be eligible to receive total body irradiation.
• Juvenile Myelomonocytic leukemia (JMML) with 10% should have AML induction therapy with disease response to partial remission (PR) (defined as > 50% reduction in mass size after therapy).
• Patients with adequate organ function and performance status criteria as measured by:
• Karnofsky score > or = to 70 % or Lansky score > or = to 70%
• Renal: Calculated creatinine clearance > or = to 60 ml/min
• Hepatic: Total bilirubin or = to 2.5
• Pulmonary: Pulmonary function (spirometry and corrected DLCO) > or = to 60% normal if available (in small children use History and Physical and CT scan as necessary to determine pulmonary status)
• Cardiac: Left ventricular ejection fraction > or = to 50%
• Double Unit Umbilical Cord Blood Grafts:

Units will be selected based on the HLA match to the patient and on the basis of the individual and combined cell doses of the units.

• Patient has a related or unrelated volunteer donor that is suitably HLA matched and available in the required time period.
• Patient is a candidate for an autologous stem cell transplant.
• Active CNS leukemia.
• Acute Myelogenous Leukemia in greater than CR2.
• Acute Myelogenous Leukemia evolved from myelofibrosis.
• Acute Lymphoblastic Leukemia, acute undifferentiated leukemia, biphenotypic leukemia or infant leukemia greater than CR3.
• Any acute leukemia with:
• Morphologic relapse or persistent disease in the BM (cytogenetic relapse without morphologic evidence of relapse or cytogenetic persistent disease in the BM is acceptable); or
• Active extra-medullary leukemia; or
• Requiring greater than 2 cycles of chemotherapy to obtain present remission status;
• Bone Marrow aplasia (defined as BM cellularity less than 5% at transplant work-up); or
• MDS with greater than 10% bone marrow blasts refractory to chemotherapy; or
• CML in blast crisis; or
• NHL refractory to chemotherapy (less than PR after 2 or more regimens); or
• Prior autologous or allogeneic HSC transplant at any time; or
• Prior radiation therapy rendering patient ineligible for TBI; or
• Uncontrolled viral, bacteria or fungal infection at time of study enrollment; or
• Seropositive or NAT positive for HIV; or
• Females who are pregnant or breast feeding; or
• Patient or guardi