A Study of the Effect of Blood Stem Cell Transplant After Chemotherapy Alone in Patients With Fanconi Anemia

Inclusion Criteria:

- Patients must have a diagnosis of Fanconi anemia (confirmed by mitomycin C or
diepoxybutane [DEB] chromosomal breakage testing at a CLIA approved laboratory).

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 10^9/L or platelet transfusion dependence*

2. ANC <1000 x 10^9/L

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

2. Myelodysplastic Syndrome (MDS) (Appendix 1: MDS Classification)

MDS at any stage, based on either one of the following classifications:

- WHO Classification

- Refractory anemia and transfusion dependence*

- Any of other stages

- IPSS Classification

- Low risk (score 0) and transfusion dependence*

- Any other risk groups Score > 0.5 Note that patients with chromosome 1q cytogenetic
abnormalities in the absence of morphologic dysplasia will not be considered to have
MDS.

3. Acute Myelogenous Leukemia Patients with acute leukemia are included in this trial
untreated, in remission or with refractory or relapsed disease.

* Transfusion dependence will be defined as greater than ONE transfusion of platelets
or red blood cells in the last year prior to evaluation on protocol.

Donor

Donor choices will be determined by the investigators according to institutional criteria.
Patients who will be enrolled on this protocol must have one of the following donor
choices:

HLA-compatible unrelated volunteer donors Patients who do not have a related HLA-matched
donor but have an unrelated donor who is either matched at all A, B, C and DRB1 (8/8) loci
or who is mismatched at no more than 2/8 loci (A, B, C or DRB1) (6/8) as tested by DNA
analysis (high resolution), will be eligible for entry on this protocol.

HLA-mismatched Related donors Patients who do not have a related or unrelated
HLA-compatible donor must have a healthy family member who is at least HLA-haplotype
identical to the recipient. First degree related donors must have a normal DEB test.

The donor must be healthy and willing and able to receive a 4-6 day course of G-CSF and
undergo 1-3 daily leukaphereses, as per institutional guidelines.

Related and unrelated donors must be medically evaluated and fulfill the criteria for
collection of PBSCs as per institutional guidelines.

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) LVEF at rest must be ≥ 50% and must
improve with exercise or 2) Shortening Fraction ≥ 29%

2. Hepatic: < 5 x 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 m^2

4. Pulmonary: asymptomatic or if symptomatic, DLCO > 50% of predicted (corrected for
hemoglobin) Each patient must be willing to participate as a research subject and must
sign an informed consent form. Parent or legal guardians of patients who are minors
will sign the informed consent form. Assents will be obtained as per institutional
guidelines.

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. Positive pregnancy test results will be reported to the
parent(s) or guardian of minor participants, as required per institutional guidelines.

Exclusion Criteria:

Active CNS leukemia Female patients who are pregnant (positive serum or urine HCG) or
breast-feeding. Women of childbearing age must avoid becoming pregnant while on study.

Active uncontrolled viral, bacterial or fungal infection Patient seropositive for HIV-I/II;
HTLV -I/II