• incidence of hematopoietic recovery and engraftment [ Time Frame: at day 42 after HCT ] [ Designated as safety issue: No ]
  

• - Incidence of secondary graft failure [ Time Frame: at day 100 after HCT ] [ Designated as safety issue: No ]
  
• - Incidence of acute graft-versus-host disease (GVHD) [ Time Frame: at 100 days after HCT ] [ Designated as safety issue: No ]
  
• - Incidence of chronic GVHD [ Time Frame: at 1 year after HCT ] [ Designated as safety issue: No ]
  
• - Incidence of regimen-related toxicity (RRT) [ Time Frame: at 1 year after HCT ] [ Designated as safety issue: No ]
  
• - Immune reconstitution [ Time Frame: over the first two years after HCT ] [ Designated as safety issue: No ]
  
• Probability of survival [ Time Frame: at 1 and 2 years after HCT ] [ Designated as safety issue: No ]
  

Procedure: Hematopoietic Stem Cell Transplant
Certain cancers can be treated by giving patients stem cells that come from someone else. This is called a stem-cell transplant. As part of the transplant process, patients receive high doses of chemotherapy and/or radiation to treat their underlying disease, such as cancer. As one of its effects, this treatment also kills the healthy stem cells that are already in the marrow. The transplant provides new stem cells for the patient from a healthy donor; that replace the bone marrow and allow the blood counts to recover.
Procedure: Thymic Shielding
protecting the thymus during radiation
Procedure: Total Body Irradiation
Six days before the stem cells are given (day -6), subjects will receive total body irradiation with thymic shielding. Thymic shielding is done by placing a piece of lead on the chest during the irradiation treatment so that the irradiation beams do not go to the thymus.
Drug: Cyclophosphamide, Fludarabine
Day -5 through Day -2, subjects will receive a chemotherapy regimen of Fludarabine, Cyclophosphamide via central line

All subjects will be given the same treatment regimen of TBI, Fludarabine, Cyclophosphamide, and ATG, followed by an alternate donor stem cell transplant. Since this treatment regimen has been given before, without thymic shielding, we will compare the outcomes of these patients with the historical data from subjects who did not receive thymic shielding.

Inclusion Criteria:

• Patients must be <18 years of age with a diagnosis of Fanconi anemia.
• Patients must have an HLA-A, B, DRB1 identical unrelated donor or ≤1 antigen mismatched related (non-HLA-matched sibling) or <1 antigen mismatched unrelated UCB donor. Patients and donors will be typed for HLA-A and B using serological or molecular techniques and for DRB1 using high resolution molecular typing.

• Patients with FA must have aplastic anemia (AA), myelodysplastic syndrome without excess blasts, or high risk genotype as defined below.

  • Aplastic anemia is defined as having at least one of the following when not receiving growth factors or transfusions
  • Platelet count <20 x 109/L
  • ANC <5 x 108/L
  • Hgb <8 g/dL
  • Myelodysplastic syndrome with multilineage dysplasia with or without chromosomal anomalies
  • High risk genotype (e.g. IVS-4 or exon 14 FANCC mutations, or BRCA1 or 2 mutations)

• Adequate major organ function including

  • Cardiac: ejection fraction >45%
  • Hepatic: bilirubin, AST/ALT, ALP <2 x normal
  • Karnofsky performance status >70% or Lansky >50%
• Women of child-bearing age must be using adequate birth control and have a negative pregnancy test

Exclusion Criteria:

• Available HLA-genotypically identical related donor
• History of gram negative sepsis or systemic fungal infection (proven or suspected based on radiographic studies)
• Refractory anemia with excess blasts, or leukemia
• Active CNS leukemia at time of HCT
• History of squamous cell carcinoma of the head/neck/cervix within 2 years of HCT
• Pregnant or lactating female
• Prior radiation therapy preventing use of TBI 450 cGy