HSCT for Patients With Fanconi Anemia Using Risk-Adjusted Chemotherapy

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 SevereIsolated Single Lineage Cytopenia and at least one of the following features:

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

3. ANC <1000 x 109/L

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

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

6. Acute Myelogenous Leukemia (untreated, in remission or with refractory orrelapsed disease)

• Donors will be either human leukocyte antigen (HLA) compatible unrelated orHLA-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 ejectionfraction (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 < 2.0mg/dl total serum bilirubin.

3. Renal: serum creatinine <1.5 mg/dl or if serum creatinine is outside the normalrange, 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 aninformed consent form.

• Female patients and donors must not be pregnant or breastfeeding at the time ofsigning consent. Women must be willing to undergo a pregnancy test prior totransplant 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