title: The role of thiotepa in allogeneic bone marrow transplantation for genetic diseases.
abstract: Graft-versus-host disease (GVHD), graft rejection, disease recurrence and long-term toxicity remain significant obstacles to successful allogeneic bone marrow transplantation (BMT) in children with genetic diseases. In an attempt 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 investigated 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 hemolytic anemia (CIHA), Gaucher's disease, Niemann-Pick disease, Hurler's syndrome, and adrenoleukodystrophy. The conditioning regimen consisted of BU 4 mg/kg 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 the standard conditioning regimen of BU-CY in the management of children suffering from these conditions.
authors.affiliation: Department of Bone Marrow Transplantation and The Cancer and Immunobiology Research Center, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: F
authors.initials: F
authors.lastname: Rosales
authors.forename: N
authors.initials: N
authors.lastname: Peylan-Ramu
authors.forename: G
authors.initials: G
authors.lastname: Cividalli
authors.forename: G
authors.initials: G
authors.lastname: Varadi
authors.forename: R
authors.initials: R
authors.lastname: Or
authors.forename: E
authors.initials: E
authors.lastname: Naparstek
authors.forename: S
authors.initials: S
authors.lastname: Slavin
authors.forename: A
authors.initials: A
authors.lastname: Nagler
mesh_terms: D000293:Adolescent; D000477:Alkylating Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D002066:Busulfan / Q000494:pharmacology* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000494:pharmacology* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D030342:Genetic Diseases, Inborn / Q000628:therapy*; D006084:Graft Rejection / Q000517:prevention & control; D006086:Graft vs Host Disease / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007223:Infant; D008212:Lymphocyte Depletion; D008297:Male; D013852:Thiotepa / Q000494:pharmacology* / Q000627:therapeutic use; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D000477:Alkylating Agents; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D013852:Thiotepa; D002066:Busulfan