Trial Information

Umbilical Cord Blood Transplant for Children With Myeloid Hematological Malignancies (UCAML)

The following will be given as the conditioning regimen for the transplant:

BUSULFAN: Busulfan (intravenous BUSULFEX) dosing will be as follows: patients <12 kg: 1.1
mg/kg/dose IV every 6 hours for 16 doses total; patients >12 kg: 0.8 mg/kg/dose IV every 6
hours for 16 doses. Administration and pharmacokinetic monitoring will be performed as per
standard practice. Anticonvulsants will be given in accordance with standard Blood and
Marrow Transplant Program recommendations.

CYCLOPHOSPHAMIDE: Cyclophosphamide (50 mg/kg/dose) will be given IV on day -5, - 4, -3, and
-2 over 2 hours. The total dose to be given over 4 days is 200 mg/kg. Mesna will be given in
accordance with standard Blood and Marrow Transplant.

FLUDARABINE: Fludarabine 40 mg/m2 will be given I.V. daily over 1 hour for 3 days.
Preparation, administration and monitoring will be according to standard practice procedure.

POST TRANSPLANT IMMUNOSUPPRESSION:

- CSA will begin on day -3. For children <40 kg, the initial dose will be 2.5 mg/kg IV
over 2 hours every 12 hours. Dose adjustments will be made to maintain levels above
200ng/ml. Levels will be done on day 0 and then as clinical indicated. CSA will be
tapered per institutional SOP. Once the patient can tolerate oral medications and has
a normal gastrointestinal transit time, CSA will be converted to an oral form.

- MMF will begin on day 0 at a dose of 15 mg/Kg IV or orally tid and will be discontinued
on day +45 unless GVHD is present.

CNS disease: Patients with CNS relapse or primary CNS disease that is symptomatic or
associated to radiological changes will receive additional irradiation to the craniospinal
axis.

SUPPORTIVE CARE:

- Supportive care will be provided as per standard practice of the Blood and Marrow Stem
Cell Transplant program at the Texas Children's Hospital, including all prophylactic
and therapeutic clinical care issues. These practices may be modified if necessary for
any individual patient in order to provide optimum care for that particular patient.

- IVIG: Intravenous immunoglobulin (500mg/kg per dose) will be given monthly until
discontinuation of GVHD therapy and documentation of antibody production.

- CB-CTLs: Patients enrolled in this protocol may also be eligible for infusion of
CB-derived multivirus-specific CTL to provide virus-specific immune reconstitution and
treatment of viral infections after CBT.

EVALUATIONS DURING THE STUDY:

Screening Procedures; Pre-HCT:

- Physical examination

- Pregnancy Test

- Complete blood count and chemistries

- Electrocardiogram

- Viral tests

- Bone marrow aspirate and biopsy/Lumbar puncture

- Renal Function (GFR)

- Lumbar puncture will be performed

- Pulmonary Function Test

EVALUATIONS BETWEEN DAY 0 AND DAY 100:

- Physical examination

- Complete blood count and chemistries

- Peripheral blood for STRs or FISH analysis for molecular diagnostics

- Lymphocyte phenotype testing and lymphoproliferative responses

- Bone marrow aspirate and biopsy for assessment of leukemia status and UCB engraftment

- Lumbar puncture

- immunoglobulins

EVALUATIONS AFTER DAY 100:

- Physical examination

- Complete blood count and chemistries

- Peripheral blood with assessment of engraftment by STRs or FISH analysis and enzyme
levels

- Echocardiograph with LVEF

- Bone marrow aspirate and biopsy assessment of leukemia status and UCB engraftment

- Lymphocyte phenotype testing (CD3, CD4, CD8, CD14, CD19 and CD56) and
lymphoproliferative responses Immunoglobulins

FOLLOW-UP INTERVAL:

Patients will be seen in the hospital everyday until discharge. After discharge from the
hospital, the patient will be following on the BMT clinics on a regular basis as recommended
by the primary physician.