HSCT for Patients With Fanconi Anemia Using Risk-Adjusted Chemotherapy

The trial proposed is a three arm phase II treatment protocol designed to investigate the
safety and efficacy of risk-adjusted chemotherapy-based cytoreductive regimen plus a CD34+
selected T-cell depleted peripheral blood stem cell (PBSC) stem cell transplant for the
treatment of patients with Fanconi anemia and severe hematologic disease. Candidates for this
trial will include patients with Fanconi anemia presenting with severe marrow failure
(transfusion dependent) or myelodysplastic syndrome, or acute myelogenous leukemia for whom
an allogeneic stem cell transplant is indicated.

Inclusion Criteria:

- Patients must have a diagnosis of Fanconi anemia

- Patients must have one of the following hematologic diagnoses:

1. Severe Aplastic Anemia (SAA), with bone marrow cellularity of <25% OR Severe
Isolated Single Lineage Cytopenia and at least one of the following features:

1. Platelet count <20 x 109/L or platelet transfusion dependence*

2. ANC <1000 x 109/L

3. Hgb <8 gm/dl or red cell transfusion dependence*

2. Myelodysplastic Syndrome (MDS) (based on WHO or IPSS Classification

3. Acute Myelogenous Leukemia (untreated, in remission or with refractory or
relapsed disease)

- Donors will be either human leukocyte antigen (HLA) compatible unrelated or
HLA-genotypically matched related donors (no fully matched sibling donor).

- Patients and donors may be of either gender or any ethnic background.

- Patients must have a Karnofsky adult, or Lansky pediatric performance scale status >
70%.

- Patients must have adequate physical function measured by:

1. Cardiac: asymptomatic or if symptomatic then 1) left ventricular ejection
fraction (LVEF) at rest must be > 50% and must improve with exercise or 2)
Shortening Fraction > 29%

2. Hepatic: < 5 x upper limit of normal (ULN) alanine transaminase (ALT) and < 2.0
mg/dl total serum bilirubin.

3. Renal: serum creatinine <1.5 mg/dl or if serum creatinine is outside the normal
range, then CrCl > 50 ml/min/1.73 m2

4. Pulmonary: asymptomatic or if symptomatic, DLCO > 50% of predicted

- Each patient must be willing to participate as a research subject and must sign an
informed consent form.

- Female patients and donors must not be pregnant or breastfeeding at the time of
signing consent. Women must be willing to undergo a pregnancy test prior to transplant
and avoid becoming pregnant while on study.

Exclusion Criteria:

- Active CNS leukemia

- Female patients who are pregnant (positive serum or urine HCG) or breast-feeding.

- Active uncontrolled viral, bacterial or fungal infection

- Patient seropositive for HIV-I/II; HTLV -I/II