Myeloablative Allogeneic Stem Cell Transplantation Using a Naive T-Cell Depleted Peripheral Blood Stem Cell Graft

The primary objectives will be to measure the safety and efficacy of allogeneic stem cell transplantation using a peripheral blood stem cell graft that has been depleted of CD45RA+ Naive T-cells.

The secondary objectives will be to measure the pace of immune recovery.

A cohort of patients (Cohort 1) will be enrolled to receive the currently accepted standard approach to myeloablative allogeneic stem cell transplantation. With the exception of volume and/or plasma depletion (in cases of donor/recipient ABO incompatibility), the peripheral blood stem cell graft will be unmodified. The primary purpose of Cohort 1 is to prospectively collect samples for measurement of immune recovery from a relatively homogeneous population of patients treated in a uniform manner. Within the limitations of age-matching, patients accrued to Cohort 1 will be incorporated into a larger retrospective historical control group for purposes of comparison with Cohort 2 of the incidence of grade II-IV acute Graft versus Host disease. The experimental aspects of this trial will be the use of a naïve T-cell depleted peripheral blood stem cell graft (Cohort 2). All other aspects of this stem cell transplantation are in line with the standard of care. Recruitment to this trial will be stratified by donor type as matched sibling or matched unrelated donor. Patients will be conditioned with total body irradiation (1350cGy) and Cyclophosphamide. The donor stem cell grafts will come from mobilized peripheral blood of 6/6 HLA-identical family members or 8/8 (HLA A, B, C, DRB1) allele-level matched unrelated donors.

Eligibility Criteria:
Inclusion Criteria:

* Age 18 to 65 years.
* 8/8 or 7/8 HLA-identical matched sibling OR Allele level 8/8 (HLA-A, B, C, DRbeta1) matched unrelated donor.
* Patients with high risk ALL in first complete remission, with high risk being defined by the presence of t(4;11), t(9;22) or t(1;19) or patients presenting with extreme hyperleukocytosis (WBC\>500,000/ml) or partial remission after initial induction therapy.
* Adult patients with acute non-lymphocytic Leukemia (ANLL) in first complete remission with high-risk cytogenetics (monosomy chromosome 5 or 7, del(5q), abn(3q26), complex karyotypic abnormalities) or failure to achieve complete remission after standard induction therapy.
* All patients with ALL or ANLL in second or subsequent remission or partial remission (\<5% blasts in bone marrow as measured by flow cytometry).
* All patients with CML in chronic (failed interferon and/or Gleevec) or accelerated phase.
* Patients with myelodysplastic syndrome with International Prognostic Scoring System (IPSS) risk category of INT-1 or greater.
* Myelofibrosis with myeloid metaplasia
* Patients with severe aplastic anemia must have failed immunosuppressive therapy such as cyclosporine plus anti-thymocyte globulin.
* Patients with a history of CNS disease must have been treated and have no active CNS disease at the time of protocol treatment.
* ECOG performance status \<2
* Patients must have adequate function of other organ systems as measured by:
* Creatinine clearance (by Cockcroft Gault equation \[Appendix IV\]) \> 30ml/min. Hepatic transaminases (ALT/AST) \< 4 x normal, bilirubin \< 2.0 mg/dl.
* Pulmonary function tests demonstrating FVC and FEV1 of \>50% of predicted for age and DLCO \> 50% of predicted.
* Ejection fraction of \>45% by echocardiogram, radionuclide scan or cardiac MRI.
* Patients must be HIV negative.
* Patients must not be pregnant.

Exclusion Criteria:

* Patients with \> 5% blasts in bone marrow or peripheral circulation.
* Patients with rapidly progressive ANLL or ALL.