Complete substitution of cyclophosphamide by fludarabine and ATG in a busulfan-based preparative regimen for children and adolescents with β-thalassemia

Children and adolescents with homozygous beta-thalassemia can be cured by transplantation of normal stem cells after eradication of the thalassemic hematopoietic system. In an attempt to achieve durable engraftment and to minimize regimen-related toxicity (RRT), we have initiated a fludarabine-based pilot protocol not containing cyclophosphamide. Between 1999 and 2004, five children with beta-thalassemia major were enrolled. Median age at transplantation was 11.5 years (range 4-14 years). Three patients received conditioning with fludarabine (30mg/m²/day × 6), oral busulfan (3.5mg/kg/day × 4), and ATG rabbit Fresenius (10mg/kg/day × 4). Two children received intravenous busulfan instead of oral busulfan at a dose of 2 × 1.4mg/kg/day × 4 days. All children were transplanted with a fresh bone marrow graft from an HLA-identical sibling. Mean cell doses given were 3.7 × 10⁸ nucleated cells/kg BW (range 2.4-6.2 × 10⁸/kg). Overall, 5/5 patients achieved donor engraftment and are alive and well. No GVHD exceeding grade I was observed, and 2/5 children maintained donor chimerism at 100%. One patient maintains mixed hematopoietic donor chimerism being between 94 and 97% nearly 5 years after transplant.