Nonmyeloablative Hematopoietic Cell Transplantation for Patients With Fanconi Anemia Using Alternative Marrow Donors: A Phase II Dose-Finding Study

Inclusion Criteria:

- Any patient with FA and bone marrow (BM) failure involving 2 of the following 3
lineages: granulocyte count < 0.5 x 10^9/L, platelet count < 20 x 10^9/L, or
hemoglobin < 8 g/dL

- Any patient with FA who requires red blood cell or platelet transfusions because of
marrow failure

- Any patient with FA who has a life-threatening BM failure involving a single
hematopoietic lineage

- Any patient with FA and pre-existing cytogenetic abnormality including hematopoietic
malignancy (acute myeloid leukemia [AML] or myelodysplastic syndrome [MDS]) in
morphological remission (defined as absence of circulating blasts and bone marrow
blasts < 5% as assessed by morphology); Note that hematopoietic recovery is not
required for remission status

- Patients must have a negative cytotoxic cross match with donor

- DONOR: Related, human leukocyte antigen (HLA)-haploidentical donors must be identical
for one HLA haplotype and mismatched for any number of HLA-A, -B, -C, DRB1 or DQB1
loci of the unshared haplotype

- DONOR: Unrelated, HLA-matched donors must be matched at HLA-A, B, C, DRB1 and DQB1 by
Deoxyribonucleic acid (DNA) typing at the highest resolution routinely available at
the time of donor selection; a single allele mismatch at HLA-A, B, or C is allowed OR
a single DQB1 mismatch is allowed

- DONOR: Bone marrow will be the only allowed hematopoietic stem cell source

- DONOR: Haploidentical donor selection will be based on standard institutional
criteria, otherwise no specific prioritization will be made amongst the suitable
available donors

Exclusion Criteria:

- Patients having available HLA-matched related donors

- Significant organ dysfunction that would prevent compliance with conditioning, GVHD
prophylaxis, or would severely limit the probability of survival, such as liver
disease/failure (active hepatitis, moderate to severe portal fibrosis/cirrhosis
confirmed by biopsy or uncorrectable hepatic synthetic dysfunction), lung disease, or
cardiac disease (ejection fraction < 35%, or if unable to obtain ejection fraction,
shortening fraction of < 26%; if shortening is < 26% a cardiology consult is required
with principal investigator [PI] having final approval of eligibility)

- Human immunodeficiency virus (HIV) seropositive patients

- Fertile females who are unwilling to use contraceptive techniques during and for the
twelve months following treatment, as well as females who are pregnant or actively
breast feeding

- Fertile males who are unwilling to use contraceptive techniques during and for the
twelve months following treatment

- AML/MDS in morphological relapse, defined as having circulating blasts or bone marrow
blasts >= 5% as assessed by morphology

- Active infectious disease concerns

- Karnofsky performance score < 50 or Lansky performance score < 40

- DONOR: Donors found to have Fanconi Anemia based on chromosomal breakage analysis

- DONOR: Donors who are not expected to meet the minimum target dose of marrow cells (1
x 10^8 nucleated cells/kg recipient ideal body weight [IBW]) or who are unwilling to
be bone marrow donors

- DONOR: HIV-positive donors

- DONOR: Donors who are cross-match positive with recipient

- DONOR: Recipient homozygous at mismatched locus; if the recipient is homozygous at
HLA-A, B, or C and the donor is mismatched at that locus, the donor should be
avoided; exceptions must be discussed with the primary investigator (PI)