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Radiosensitivity in Fanconi anemia: application to the conditioning for bone marrow transplantation.
Fanconi anemia is characterised by pancytopenia, malformations and chromosomal breaks probably related to a congenital defect of DNA repair mechanisms. The evolution is always fatal unless, the patient receives a bone marrow transplant from an HLA identical sibling. According to preliminary work on sensitivity of FA cells to alkylating agents and to in vivo radiosensitivity tests, we used a modified conditioning regimen with cyclophosphamide 20 mg/kg and 5 Grays thoraco-abdominal irradiation. Nineteen patients are reported. The actuarial survival is 74% with a median follow-up time of 4 years (range 6 months to 6 years). GVH was the main complication (58%). It was responsible directly or indirectly for 4 deaths. These results show that BMT in FA is successful in the large majority of cases. The decrease of the dose cyclophosphamide allowed a good engraftment without major toxicity. Studies are in progress for using this type of protocol in situations without a HLA matched sibling donor.
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