A Pilot Trial of Clofarabine Added to Standard Busulfan and Fludarabine for Conditioning Prior to Allogeneic Hematopoietic Cell Transplantation

Inclusion Criteria:

- Patients must be ≥ 3 months and ≤30 years of age.

- Stratum A: Non-Malignant Diseases, including:

- Bone Marrow Failure Syndromes

- Hemoglobinopathies or transfusion-dependent RBC defects

- Congenital Immunodeficiencies

- Metabolic Diseases known to be treatable with HCT (e.g. Hurler's)

- Other Bone Marrow Stem Cell Defects (e.g. Osteopetrosis)

- Severe Immune Dysregulation / Autoimmune Syndromes with at least transient prior
response to immunosuppressive therapy

- Stratum B: Myeloid Malignancies, including:

- AML, in greater than first clinical remission, or in CR1 but with detectable
disease (≥0.1% Blasts by MRD or Flow, or Positive Cytogenetics), or in CR1 but
with a matched sibling UCB donor.

- MDS

- JMML

- CML, with detectable disease by PCR

- Patients must have a suitable donor based on the UCSF Pediatric BMT SOP. 10/10
(HLA-A, -B, -C, -DR, -DQ) matching will be done for related and adult unrelated
donors; 8/8 (HLA-A, -B, -C, -DR) for umbilical cord blood donors. Patients with
non-malignant diseases will generally be eligible only if they have a mismatched
donor, or an accepted clinical reason to be considered high-risk for rejection.

- Liver transaminases (AST/ALT) and Direct Bilirubin less than twice the upper limit of
normal within 2 weeks of admission.

- Cardiac Shortening Fraction ≥27% within 4 weeks of admission.

- Creatinine clearance by Schwartz formula, GFR or 24 hr urine collection ≥50
cc/min/1.73 m2, within 4 weeks of admission.

- Pulmonary diffusion capacity ≥50% of predicted corrected for anemia/lung volume
within 4 weeks of admission. If unable to do PFT's, then no active lung disease by
CXR and/or O2 Sat ≥90% on room air.

Exclusion Criteria:

- Fanconi Anemia

- Dyskeratosis Congenita

- A known syndrome with increased sensitivity to radiation or alkylating agents

- Severe Combined Immunodeficiency Disease eligible for a non-myeloablative HCT trial

- A mismatched donor for whom ex vivo T-cell depletion of the donor stem cells is
planned