Total body irradiation, thiotepa, and cyclophosphamide as a conditioning regimen for children with acute lymphoblastic leukemia in first or second remission undergoing bone marrow transplantation with HLA-identical siblings

Purpose: Allogeneic hematopoietic stem-cell transplantation (HSCT) from HLA -identical siblings can be used to treat children with acute lymphoblastic leukemia (ALL). However, a significant proportion of patients with ALL who undergo HSCT relapse. For this reason, we prospectively evaluated a prepara tive regimen that included total body irradiation (TBI), thiotepa (TT), and cyclophosphamide (CY) in patients with high-risk ALL in first complete rem ission (CR) and in children with ALL in second CR. Patients and Methods: Forty children (median age, 9 years; range, 1 to 18 y ears) with ALL in first or second CR who underwent allogeneic HSCT from HLA -identical siblings were conditioned with a combination of fractionated TBI , TT (10 mg/kg), and CY (120 mg/kg over 2 days). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine administered intravenously at ct dose of 1 to 3 mg/kg/d for the first 21 days and subsequently orally at a dose of 6 mg/kg/d. Results: All assessable patients were engrafted, with a median time of 11 a nd 24 days for neutrophil and platelet recovery, respectively. The preparat ive regimen was well tolerated. Only one patient died as a result of regime n;related causes. Eight patients relapsed at a median time of 8 months afte r transplantation (range, 3 to 9 months), and this: determined a cumulative probability of relapse of 23%. Twenty-six of 40 patients (65%) are alive a nd in complete hematologic remission, with a median observation time of 36 months (range, 14 to 57 months), which results in a disease-free survival ( DFS) at 3 years of 65%, The 13 patients-who underwent transplantation in fi rst CR held ct DFS of 85%, whereas the 27 patients who underwent HSCT in se cond CB had a DFS of 56%. Conclusion: These data suggest that TT is an effective cytotoxic drug that can be safely added to the classical TBI-CY regimen. Because of its cell cy cle-independent action, good CNS diffusion, and limited extramedullary toxi city, TT may contribute to increasing the percentage of children with ALL w ho are successfully cured with allogeneic BMT, (C) 1999 by American Society of Clinical Oncology.