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.

  • Letter to the Editor
  • Published:

Using reduced intensity conditioning and HLA-identical sibling donors, antithymocyte globulin increases the risk of relapse, which can be overcome by a high stem cell dose

Bone Marrow Transplantation volume 42, pages 769–771 (2008)Cite this article

In this study, we analyzed the effect of inclusion of antithymocyte globulin (ATG) in the reduced intensity conditioning (RIC) protocol before hematopoietic SCT with HLA-identical sibling donors. Usually, we add ATG to the conditioning protocol only when using unrelated or mismatched donors,1 but in the RIC protocol developed by Slavin et al.2 ATG is included regardless of the donor type.

The study included 52 consecutive patients with leukemia receiving RIC and hematopoietic SCT with an HLA-identical sibling donor between April 1999 and June 2007 at the Karolinska University Hospital. Patient and donor demographics are displayed in Table 1. All patients received conditioning with fludarabine (30 mg/m2 for 3–5 days) in combination with orally administered BU (total dose 8 mg/kg, n=35),2 2 Gy TBI (n=3),3 6 Gy fractionated TBI and CY (total dose 60 mg/kg, n=11),4 or treosulfan (14 g/m2 × 3, n=3). All patients, except two, given the fludarabine and BU protocol, received (n=33) ATG1 (Genzyme, Cambridge, MA, USA), at a dose of 2 mg/kg/day for 4 days with the last dose given on day −1.1, 2 All patients received GVHD prophylaxis with CsA and four doses of MTX.5 During the first month, blood CsA levels were maintained at 100–150 ng/ml.

Table 1 Characteristics of patients and donors
Full size table

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

Figure 1

References

  1. Remberger M, Svahn B-M, Hentschke P, Löfgren C, Ringdén O . Effect on cytokine release and graft-versus-host disease of different anti-T cell antibodies during conditioning for unrelated haematopoietic stem cell transplantation. Bone Marrow Transplant 1999; 24: 823–830.

    Article  CAS  PubMed  Google Scholar 

  2. Slavin S, Nagler A, Naparstek E, Kapelushnik Y, Aker M, Cividalli G et al. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood 1998; 91: 756–763.

    CAS  PubMed  Google Scholar 

  3. Storb R, Yu C, Wagner JL, Deeg HJ, Nash RA, Kiem HP et al. Stable mixed hematopoietic chimerism in DLA-identical littermate dogs given sublethal total body irradiation before and pharmacological immunosuppression after marrow transplantation. Blood 1997; 89: 3048–3054.

    CAS  PubMed  Google Scholar 

  4. Uzunel M, Remberger M, Sairafi D, Hassan Z, Mattsson J, Omazic B et al. Unrelated versus related allogeneic stem cell transplantation after reduced intensity conditioning. Transplantation 2006; 82: 913–919.

    Article  PubMed  Google Scholar 

  5. Storb R, Deeg H, Pepe M, Appelbaum F, Anasetti C, Beatty P et al. Methotrexate and cyclosporine versus cyclosporine alone for prophylaxis of graft-versus-host disease in patients given HLA-identical marrow grafts for leukemia: long-term follow-up of a controlled trial. Blood 1989; 73: 1729–1734.

    CAS  PubMed  Google Scholar 

  6. Remberger M, Svahn BM, Mattsson J, Ringden O . Dose study of thymoglobulin during conditioning for unrelated donor allogeneic stem-cell transplantation. Transplantation 2004; 78: 122–127.

    CAS  PubMed  Google Scholar 

  7. Bacigalupo A, Lamparelli T, Bruzzi P, Guidi S, Alessandrino PE, di Bartolomeo P et al. Antithymocyte globulin for graft-versus-host disease prophylaxis in transplants from unrelated donors: 2 randomized studies from Gruppo Italiano Trapianti Midollo Osseo (GITMO). Blood 2001; 98: 2942–2947.

    Article  CAS  PubMed  Google Scholar 

  8. Schmitz N, Bacigalupo A, Hasenclever D, Nagler A, Gluckman E, Clark P et al. Allogeneic bone marrow transplantation vs filgrastim-mobilised peripheral blood progenitor cell transplantation in patients with early leukaemia: first results of a randomised multicentre trial of the European group for blood and marrow transplantation. Bone Marrow Transplant 1998; 21: 995–1003.

    Article  CAS  PubMed  Google Scholar 

  9. Ringdén O, Barret J, Zhang M-J, Loberiza FR, Bolwell BJ, Cairo MS et al. Decreased treatment failure in recipients of HLA-identical bone marrow or peripheral blood stem cell transplants with high CD34 cell doses. Br J Haematol 2003; 121: 874–885.

    Article  PubMed  Google Scholar 

  10. Remberger M, Sundberg B . Rabbit-immunoglobulin G levels in patients receiving thymoglobulin as part of conditioning before unrelated donor stem cell transplantation. Haematologica 2005; 90: 931–938.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by grants from the Swedish Cancer Society (0070-B03-17XBC), the Children's Cancer Foundation (03/039), the Swedish Research Council (K2003-32X-05971-23A), the Tobias Foundation, the Stockholm Cancer Society, the Swedish Medical Society and the Karolinska Institutet.

Author information

Authors and Affiliations

  1. Department of Clinical Immunology Centre for Allogeneic Stem Cell Transplantation and Clinical Immunology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

    M Remberger, J Mattsson, B-M Svahn & O Ringdén

Authors
  1. M Remberger
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J Mattsson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B-M Svahn
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. O Ringdén
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M Remberger.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Remberger, M., Mattsson, J., Svahn, BM. et al. Using reduced intensity conditioning and HLA-identical sibling donors, antithymocyte globulin increases the risk of relapse, which can be overcome by a high stem cell dose. Bone Marrow Transplant 42, 769–771 (2008). https://doi.org/10.1038/bmt.2008.246

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2008.246

This article is cited by

Search

Advanced search

Quick links