Reduced-Intensity Conditioning (RIC) and Myeloablative Conditioning (MAC) for HSCT in AML/MDS

Inclusion Criteria for Myeloablative Conditioning Transplant

1. Patient must be between 0-22 years of age.

2. Diagnosis of acute myeloid leukemia or myelodysplastic syndrome, either high-risk,
relapsed or primary refractory, MRD-positive without circulating myeloblasts or active
extramedullary disease at the time of transplant. Active marrow disease is permitted.

("High-risk" AML features are defined by the following: greater than 15% blasts in the
bone marrow after the first course of Induction chemotherapy; adverse cytogenetic
abnormalities of monosomy 5, monosomy 7, or 5q deletion; presence of FLT3 positive
internal tandem duplication (FLT3/ITD+), particularly high allelic ratio; or
treatment-related AML.)

3. Stem cell sources include bone marrow, peripheral blood stem cells, or umbilical cord
blood.

4. Related bone marrow, peripheral blood stem cell, or cord blood unit: sibling should be
HLA-matched at A, B, and DR-B1 loci. Unrelated cord blood unit should be at a minimum
of 4/6 matched at antigen level on HLA A and B, and allele level at HLA DR-B1 loci.
Unrelated bone marrow or peripheral blood stem cell donor should be HLA allele level
matched at A, B, C, and DR-B1.

5. Minimum prefreezing cell dose for cord blood units: 3 x 107 total nucleated cells/kg
and 1.5 x 105 CD34+ cells/kg. If this is not attainable, then double cord blood
transplant should be considered.

6. Patient, parent, or legal guardian must have given written informed consent and/or
assent.

7. Patient must have adequate performance status (Lansky score ≥60% for patients <16
years; Karnofsky score ≥60% for patients ≥16 years).

8. Patient must have adequate pre-transplant organ function as defined by:

- Renal: creatinine clearance or radioisotope GFR ≥70 mL/min/1.73 m2.

- Hepatic: total bilirubin ≤2.0 mg/dL unless the increase in bilirubin is
attributable to Gilbert's syndrome; and SGOT (AST), SGPT (ALT), and Alkaline
Phosphatase <4 x upper limit of normal (ULN) for age.

- Cardiac: normal cardiac function by echocardiogram or radionuclide scan, as
defined by left ventricular ejection fraction at rest >45%, or shortening
fraction >26%.

- Pulmonary: FEV1, FVC, and DLCO (corrected for hemoglobin) ≥50% of predicted; if
unable to perform pulmonary function tests, then oxygen saturation ≥92% on room
air.

Eligibility Criteria for Reduced-Intensity Conditioning Transplant

1. Patient must be between 0 -22 years of age.

2. Patient must meet criteria #2-7 in section 5.1.

3. Patient is excluded from myeloablative conditioning transplant due to failure to meet
any of the criteria outlined in #8 of section 5.1.

4. Patient must have adequate pre-transplant organ function as defined by:

- Renal: creatinine clearance or radioisotope GFR ≥70 mL/min/1.73 m2.

- Hepatic: total bilirubin ≤2.5 mg/dL unless the increase in bilirubin is
attributable to Gilbert's syndrome; and SGOT (AST), SGPT (ALT), and Alkaline
Phosphatase <5 x upper limit of normal (ULN) for age.

- Cardiac: normal cardiac function by echocardiogram or radionuclide scan, as
defined by left ventricular ejection fraction at rest >40%, or shortening
fraction >26%.

- Pulmonary: FEV1, FVC, and DLCO (corrected for hemoglobin) ≥40% of predicted; if
unable to perform pulmonary function tests, then oxygen saturation ≥92% on room
air.

Exclusion Criteria:

Exclusion Criteria for Myeloablative Conditioning Transplant

1. Recipient of an autologous stem cell transplant.

2. Allogeneic hematopoietic stem cell transplant within the previous 3 months.

3. Uncontrolled bacterial, viral, fungal, or other infection at the time of
cytoreduction. Uncontrolled infection defined by positive blood cultures and fevers
>38.0 within 24-48 hours of start of conditioning therapy.

4. Evidence of HIV/HTLV infection or HIV/HTLV positive serology.

5. Pregnancy or lactating. All females of 11 years of age or older and/or who have begun
menstruating will be screened for HCG by either urinalysis or a blood sample in order
to screen for pregnancy status.

6. Patients with any inherited bone marrow failure syndrome (including, but not limited
to, Fanconi anemia, Shwachman-Diamond syndrome, and dyskeratosis congenital) or Down
syndrome (defined as either constitutional trisomy 21 or constitutional mosaicism of
trisomy 21).