Results Of Transplantation Of Hematopoetic Stem Cells In Children With Fanconi Anemia.

Fanconi anemia is an autosomal recessive disorder characterized by multiple congenital anomalies, progressive bone marrow failure, and susceptibility to malignant neoplasm formation. BMT from HLA-matched donor offers the only possibility of cure for aplastic anemia in FA. 56 patients have been followed in our clinic between 1984 and 2001, 5 of them were treated with BMT from HLA-matched siblings (3 boys, 2 girls, age 7-14 years). The time interval from diagnosis to transplantation was 1-5,5 years; the follow-up period ranged from 6 months to 7 years. The preparation regimen for the first three transplantations included cyclophosphamide, 40 mg/kg and busulphan, 8 mg/kg (in two patients) or cyclophosphamide, 40 mg/kg and busulphan, 6 mg/kg (in the third patient). One patient also received antithymocyte globulin (ATGAM), 90 mg/kg. GVHD prophylaxis included cyclosporin A in two patients and daclizumab in one. A new protocol of BMT in FA has been used since 2001. The preparation regimen consists of busulphan, 4 mg/kg; fludarabine, 150 mg/m(2); and ATG, 90 mg/kg. GVHD prophylaxis included cyclosporin A, methotrexate, and daclizumab. Two hematopoetic cell transplantations from HLA-matched siblings were performed according to the new protocol. Engraftment was attained in five patients. The posttransplantation period was complicated with severe acute GVHD (III-IV degree) in the first three patients with lethal outcome in one case. Two survivers had severe chronic GVHD. If the new preparation regimen was used, mild acute GVHD (II degree) occurred in only one parent. Chronic GVHD and severe organ toxicity were observed in neither of the two patients. The four survivers have good graft function at present. The quality of life of the girl with chronic extensive GVHD is impaired with scleroderma and joint contractures. Thus, conditioning regimens used in FA patients showed good efficiency, and the of ATG instead of cyclophosphamide, as well as busulphan dose reduction allowed the organ toxicity to be minimized. Chronic GVHD or severe acute GVHD were avoided in case of the use of novel GVHD prophylaxis regimen.