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

Marco Zecca, Andrea Pession, Chiara Messina, Federico Bonetti, Claudio Favre, Arcangelo Prete, Simone Cesaro, Fulvio Porta, Ida Mazzarino, Giovanna Giorgiani, Roberto Rondelli, Franco Locatelli

Research output: Contribution to journalArticle

Abstract

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 preparative regimen that included total body irradiation (TBI), thiotepa (TT), and cyclophosphamide (CY) in patients with high-risk ALL in first complete remission (CR) and in children with ALL in second CR. Patients and Methods: Forty children (median age, 9 years; range, 1 to 18 years) 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 a 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 and 24 days for neutrophil and platelet recovery, respectively. The preparative regimen was well tolerated. Only one patient died as a result of regimen-related causes. Eight patients relapsed at a median time of 8 months after transplantation (range, 3 to 9 months), and this determined a cumulative probability of relapse of 23%. Twenty-six of 40 patients (65%) are alive and 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 first CR had a DFS of 85%, whereas the 27 patients who underwent HSCT in second CR 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 cycle-independent action, good CHS diffusion, and limited extramedullary toxicity, TT may contribute to increasing the percentage of children with ALL who are successfully cured with allogeneic BMT.

Original languageEnglish
Pages (from-to)1838-1846
Number of pages9
JournalJournal of Clinical Oncology
Volume17
Issue number6
Publication statusPublished - Jun 1999

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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