Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

TBI, etoposide and cyclophosphamide as a promising conditioning regimen for BMT in childhood ALL in second remission

Bone Marrow Transplantation volume 26, pages 1260–1262 (2000)Cite this article

With its strong anti-leukaemic activity and propensity for diffusion to the central nervous system (CNS), etoposide (VP-16) has been proven to be effective when combined with TBI, with or without CY, as conditioning for BMT in acute leukaemias.123 The combined use of a topoisomerase inhibitor (VP-16) together with an alkylating agent (CY) in a TBI-based conditioning regimen may represent an effective approach towards virtually eliminating the leukaemic clone.2 Most available data concern experiences in adult patients, while little information is available in children.123456789 However, a recent study published in this journal, proved the feasibility and efficacy of TBI-VP 16-CY in paediatric patients with different types of acute leukaemias at various stages.10 Our single-centre experience confirms the safety and efficacy of this conditioning regimen in children with ALL in 2nd CR, demonstrated by the transplanted-related mortality (TRM) and disease-free survival (DFS) estimations.

Between April 1995 and December 1999, 28 children with ALL in 2nd CR, underwent either allogeneic BMT from an HLA-identical sibling (12 patients) or autologous stem cell transplantation (four BM and 12 PBSC). Informed consent was obtained for all children, signed by their parents. For patients who received autologous PBSC grafts from 1997 onwards, peripheral blood (CD34+) progenitor cells were selected adopting a new two-step negative purification method.11 All patients were given intensive chemotherapy first-line protocols at diagnosis, according to BFM schedules.1213 Site of relapse among patients undergoing allogeneic BMT was BM in six cases, BM plus CNS in two, BM plus testis in one and isolated CNS in three cases. In the autologous transplantation group, site of relapse among patients undergoing PBSC was BM in six, BM plus CNS in one, BM plus other sites (eyes or testis) in two cases, CNS isolated in one case and testis isolated in two cases, and among those undergoing ABMT was BM in two cases and BM plus CNS in two cases. The median time from diagnosis to relapse was 26 months (range 11–102 months) and 36 months (range 15–78 months) for allogeneic and autologous transplantation, respectively. All patients underwent second-line chemotherapy after relapse, based on an induction schedule with idarubicin and Ara-C14 and a 2 to 3 month consolidation course according to BFM chemotherapy protocols.15

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. Blume KG, Forman SJ, O'Donnel MR et al. Total body irradiation and high-dose etoposide: a new preparatory regimen for bone marrow transplantation in patients with advanced hematologic malignancies Blood 1987 69: 1015–1020

    CAS  PubMed  Google Scholar 

  2. Blume KG, Long GD, Negrin RS et al. Role of etoposide (VP-16) in preparatory regimens for patients with leukemia or lymphoma undergoing allogeneic bone marrow transplantation Bone Marrow Transplant 1994 14: (Suppl. 4) S9-S10

    Google Scholar 

  3. Brown RA, Wolff SN, Fay JW et al. High-dose etoposide, cyclophosphamide, and total body irradiation with allogeneic bone marrow transplantation for patients with acute myeloid leukemia in untreated first relapse: a study by the North American Marrow Transplant Group Blood 1995 85: 1391–1395

    CAS  PubMed  Google Scholar 

  4. Bostrom B, Weisdorf DJ, Kim T et al. Bone marrow transplantation for advanced acute leukemia: a pilot study of high-energy total body irradiation, cyclophosphamide and continuous infusion etoposide Bone Marrow Transplant 1990 5: 83–89

    CAS  PubMed  Google Scholar 

  5. Giralt SA, Le Maistre CF, Vriesendorp HM et al. Etoposide, cyclophosphamide, total-body irradiation, and allogeneic bone marrow transplantation for hematologic malignancies J Clin Oncol 1994 12: 1923–1930

    Article  CAS  Google Scholar 

  6. Cole CH, Pritchard S, Rogers PCJ et al. Intensive conditioning regimen for bone marrow transplantation in children with high-risk haematological malignancies Med Pediatr Oncol 1994 23: 464–469

    Article  CAS  Google Scholar 

  7. Horstmann M, Kroschke G, Stockschlader M et al. Earlytoxicity of intensified conditioning with etoposide combinedwith total body irradiation/cyclophosphamide or busulfan/cyclophosphamide in children undergoing autologous or allogeneic bone marrow transplantation Pediatr Hematol Oncol 1996 13: 45–53

    Article  CAS  Google Scholar 

  8. Kroger N, Kruger W, Wacker-Backhaus G et al. Intensified conditioning regimen in bone marrow transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia Bone Marrow Transplant 1998 22: 1029–1033

    Article  CAS  Google Scholar 

  9. Pirich L, Haut P, Morgan E et al. Total body irradiation, cyclophosphamide, and etoposide with stem cell transplant as treatment for infants with acute lymphoblastic leukemia Med Pediatr Oncol 1999 32: 1–6

    Article  CAS  Google Scholar 

  10. Duerst RE, Horan JT, Liesveld JL et al. Allogeneic bone marrow transplantation for children with acute leukemia: cytoreduction with fractionated total body irradiation, high-dose etoposide and cyclophosphamide Bone Marrow Transplant 2000 25: 489–494

    Article  CAS  Google Scholar 

  11. Rambaldi A, Borleri G, Dotti G et al. Innovative two-step negative selection of granulocyte colony-stimulating factor-mobilized circulating progenitor cells: adequacy for autologous and allogeneic transplantation Blood 1998 91: 2189–2196

    CAS  PubMed  Google Scholar 

  12. Riehm H, Gadner H, Henze G et al. Results and significance of six randomized trials in four consecutive ALL-BFM studies Hematology and Blood Transfusion, part 2: Acute Leukemias Vol. 33: Springer: Berlin 1990 pp 439–450

    Google Scholar 

  13. Conter V, Aricò M, Valsecchi MG et al. Extended intrathecal methotrexate may replace cranial irradiation for prevention of CNS relapse in children with intermediate-risk acute lymphoblastic leukemia treated with Berlin–Frankfurt–Munster–based intensive chemotherapy J Clin Oncol 1995 13: 2497–2502

    Article  CAS  Google Scholar 

  14. Giona F, Testi AM, Moletti ML et al. Idarubicin plus cytosine-arabinoside (ALL R-87 protocol) in advanced acute lymphoblastic leukemia: the GIMEMA/AIEOP experience Leuk Lymphoma 1992 7: 15–19

    Article  Google Scholar 

  15. Henze G, Fengler R, Hartmann R et al. Six-year experience with a comprehensive approach of recurrent childhood acute lymphoblastic leukemia (ALL-REZ BFM 85). A relapse study of the BFM group Blood 1991 78: 1166–1172

    CAS  PubMed  Google Scholar 

  16. Balduzzi A, Gaipa G, Bonanomi S et al. Leukemia-free circulating progenitor cells assessed by molecular methods in autologous transplantation in pediatric B-ALL in 2nd CR Blood 1998 10: (Suppl. 1) 648a (Abstr. 2675)

    Google Scholar 

  17. Uderzo C, Rondelli R, Dini G et al. High-dose vincristine, fractionated total-body irradiation and cyclophosphamide as conditioning regimen in allogeneic and autologous bone marrow transplantation for childhood acute lymphoblastic leukaemia in second remission: a 7-year Italian multicentre study Br J Haematol 1995 89: 790–797

    Article  CAS  Google Scholar 

  18. Matsuyama T, Kojima S, Kato K . Allogeneic bone marrow transplantation for childhood leukemia following a busulfan and melphalan preparative regimen Bone Marrow Transplant 1998 22: 21–26

    Article  CAS  Google Scholar 

  19. Bordigoni P, Esperou H, Souillet G et al. Total body irradiation-high-dose cytosine arabinoside and melphalan followed by allogeneic bone marrow transplantation with HLA-identical siblings in the treatment of children with acute lymphoblastic leukaemia after relapse while receiving chemotherapy: a Societe Française de Greffe de Moelle study Br J Haematol 1998 102: 656–665

    Article  CAS  Google Scholar 

  20. Zecca M, Pession A, Messina C et al. 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 J Clin Oncol 1999 17: 1838–1846

    Article  CAS  Google Scholar 

  21. Bacigalupo A, van Lint MT, Occhini D et al. Increased risk of leukemia relapse with high-dose cyclosporine A after allogeneic marrow transplantation for acute leukemia Blood 1991 77: 1423–1428

    CAS  PubMed  Google Scholar 

  22. Locatelli F, Zecca M, Rondelli R 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 arandomized trial Blood 2000 95: 1572–1579

    CAS  PubMed  Google Scholar 

  23. Klingebiel T, Henze G, Ebell W et al. Bone marrow transplantation in children for ALL in 2nd and 3rd remission with preparation by TBI and etoposide Blood 1998 92: Abstr. 4512, 351b

    Google Scholar 

Download references

Acknowledgements

We would like to thank Miss Joanna Upton for her language review and linguistic consultancy, Miss Sara Vaghi for secretary support and the ‘Comitato Maria Letizia Verga per lo Studio e la Cura delle Leucemie dell'Infanzia’ for the continuous support to our research.

Author information

Authors and Affiliations

  1. Department of Pediatrics, BMT Unit, Milan-Bicocca University, San Gerardo Hospital, Monza, Italy

    E Biagi, A Rovelli, A Balduzzi, A Tagliabue & C Uderzo

  2. Department of Pediatrics, ‘Centro Operativo e di Ricerca Statistica-Fondazione Tettamanti’, Milan-Bicocca University, San Gerardo Hospital, Monza, Italy

    P De Lorenzo

Authors
  1. E Biagi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A Rovelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A Balduzzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P De Lorenzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A Tagliabue
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. C Uderzo
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Biagi, E., Rovelli, A., Balduzzi, A. et al. TBI, etoposide and cyclophosphamide as a promising conditioning regimen for BMT in childhood ALL in second remission. Bone Marrow Transplant 26, 1260–1262 (2000). https://doi.org/10.1038/sj.bmt.1702714

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1702714

This article is cited by

Search

Advanced search

Quick links