This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zecca, M. Articles by Locatelli, F. Search for Related Content PubMed PubMed Citation Articles by Zecca, M. Articles by Locatelli, F. Social Bookmarking                            What's this?

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

From the Department of Pediatrics, University of Pavia, IRCCS Policlinico San Matteo, Pavia; Department of Pediatrics, University of Bologna, Ospedale Sant'Orsola, Bologna; Department of Pediatrics, University of Padova, Padova; Department of Pediatrics, University of Pisa, Pisa; Department of Pediatrics, University of Brescia, Spedali Civili, Brescia; and Department of Pediatrics, Ospedale Silvestrini, Perugia, Italy.

Address reprint requests to Marco Zecca, MD, Dipartimento di Scienze Pediatriche, Università di Pavia, IRCCS Policlinico San Matteo, P.le Golgi 2, I-27100 Pavia, Italy; email m.zecca{at}smatteo.pv.it

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 CNS diffusion, and limited extramedullary toxicity, TT may contribute to increasing the percentage of children with ALL who are successfully cured with allogeneic BMT.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				G. La Nasa, C. Giardini, F. Argiolu, F. Locatelli, M. Arras, P. De Stefano, A. Ledda, A. Pizzati, M. A. Sanna, A. Vacca, et al. Unrelated donor bone marrow transplantation for thalassemia: the effect of extended haplotypes Blood, May 29, 2002; 99(12): 4350 - 4356. [Abstract] [Full Text] [PDF]

				N. Bunin, M. Carston, D. Wall, R. Adams, J. Casper, N. Kamani, R. King, and the National Marrow Donor Program Working Group Unrelated marrow transplantation for children with acute lymphoblastic leukemia in second remission Blood, May 1, 2002; 99(9): 3151 - 3157. [Abstract] [Full Text] [PDF]

				F. Locatelli, M. Zecca, R. Rondelli, F. Bonetti, G. Dini, A. Prete, C. Messina, C. Uderzo, M. Ripaldi, F. Porta, et al. Graft versus host disease prophylaxis with low-dose cyclosporine-A reduces the risk of relapse in children with acute leukemia given HLA-identical sibling bone marrow transplantation: results of a randomized trial Blood, March 1, 2000; 95(5): 1572 - 1579. [Abstract] [Full Text] [PDF]