TBI Dose De-escalation for Fanconi Anemia

Inclusion Criteria: Meeting the definition of standard risk or high risk Fanconi anemia as defined in the next two sections: Standard risk patients must be <18 years of age 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 * 10^9/L ANC <5 * 10^8/L Hemoglobin <8 g/dL Myelodysplastic syndrome (MDS) 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 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 hematopoietic stem cell transplant (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. Adequate major organ function including: Cardiac: ejection fraction >45% Hepatic: bilirubin, AST or ALT, 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 total body irradiation (TBI).