Bone Marrow Transplantation for Fanconi Anemia

Abstract

Fanconi anemia (FA) is an autosomal recessive inherited condition in which congenital malformations are associated with bone marrow failure. The most common abnormalities are skin pigmentation, microcephaly, short stature, skeletal defects, particularly of the lateral aspect of the forearms and hands, and kidney and cardiac malformations (Fanconi 1967; Beard 1976). Multiple abnormalities of peripheral blood lymphocyte chromosomes are almost always present. Left to follow its natural course, FA is always fatal, with death caused by progressive marrow aplasia or, less frequently, by development of acute leukemia (Swift 1976; Prindull et al. 1979). Bone marrow transplantation (BMT) has the potential to correct the stem cell defect. In the past, the outcome of transplantation in patients with FA has been poor because of the severe and prolonged toxicity of the pretransplantation conditioning regimen and subsequent graft-versus-host disease (Gluckman et al. 1980). The poor tolerance to alkylating agents has been related to a DNA repair defect leading to increased chromosomal instability. Recently, efforts have been made to modify the conditioning regimen according to cell sensitivity to alkylating agents and to irradiation.