The role of thiotepa in allogeneic bone marrow transplantation for geneticdiseases

Graft-versus-host disease (GVHD), graft rejection, disease recurrence and l ong-term toxicity remain significant obstacles to successful allogeneic bon e marrow transplantation (BMT) in children with genetic diseases, In an att empt to improve results, we used a preparative regimen consisting of three alkylating agents, busulfan (BU), thiotepa (TTP) and cyclophosphamide (CY), for T cell-depleted allogeneic bone marrow transplantation instead of the conventional BU-CY protocol, The effect of this intensified regimen was inv estigated in 26 consecutive children with genetic diseases who underwent T cell-depleted BMT from HLA-identical siblings. Sixteen patients were males and 10 females, of median age 5 (0.2-14) years, The diseases included beta- thalassemia major, osteopetrosis, severe combined immunodeficiency, Wiskott -Aldrich syndrome, familial agranulocytosis, congenital idiopathic hemolyti c anemia (CIHA), Gaucher's disease, Niemann-Pick disease, Hurler's syndrome , and adrenoleukodystrophy. The conditioning regimen consisted of BU 4 mg/k g x 4 days (-8 to -5), TTP 5 mg/kg x 2 days (-4 and -3), and CY 60 mg/kg x 2 days (-2 and -1), Engraftment was as expected, with WBC >1.0 x 10(9)/l at day +19 (10-33), ANC >0.5 x 10(9)/l at day +22 (10-56) and platelets >25 x 10(9)/l at day +32 (18-131), Transplant-related mortality was 19%. Overall survival and disease-free survival (DFS) at 60 months follow-up were both 77%, Our results with the BU-TTP-CY regimen followed by T cell-depleted BMT in genetic diseases may provide a basis for prospective comparison with th e standard conditioning regimen of BU-CY in the management of children suff ering from these conditions.