Combination Chemotherapy and Total Body Irradiation in Treating Patients with Fanconi Anemia Undergoing Donor Stem Cell Transplant

Inclusion Criteria

• Standard risk patients with a diagnosis of Fanconi anemia with 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 10^9/L ** Absolute neutrophil count (ANC) < 5 x 10^8/L ** Hemoglobin (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)
• High risk patients must have one or more of the following high risk features: * Advanced myelodysplastic syndrome (MDS) (>= 5% blast) or acute leukemia * Require additional HSCT for graft failure * History at any time of systemic fungal or gram negative infection * Severe renal disease with a creatinine clearance < 40 mL/min * Age >= 18 years
• Very high risk patients must have advanced MDS (>= 5% blast) or acute leukemia after initial HSCT
• Patients must have an appropriate source of stem cells; patients and donors will be typed for HLA-A, B, C and DRB1 using high resolution molecular typing
• Cardiac: ejection fraction > 45%
• Bilirubin < 5 x normal
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 5 x normal
• Alkaline phosphatase (ALP) < 5 x normal
• Karnofsky performance status > 70% or Lansky > 50% (if < 16 years of age)
• Women of child-bearing age must be using adequate birth control and have a negative pregnancy test
• Written consent

Exclusion Criteria

• Available HLA-genotypically identical related donor in standard risk patients
• Active central nervous system (CNS) leukemia at time of study enrollment
• History of squamous cell carcinoma of the head/neck/cervix within previous 2 years
• Prior radiation therapy that prevents further TBI