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.

  • Original Article
  • Published:

Reduced Intensity Conditioning

Reduced-intensity conditioning with busulfan and fludarabine with or without antithymocyte globulin in HLA-identical sibling transplantation – a retrospective analysis

Summary:

It is unknown whether the addition of antithymocyte globulin (ATG) to reduced-intensity conditioning with busulfan (BU) and fludarabine (FLU) is beneficial in HLA-identical sibling transplantation. Therefore, we analyzed retrospectively data on 83 patients, who received peripheral blood stem cells from HLA-identical siblings after conditioning with either 8 mg/kg BU and 150 mg/m2 FLU (n=45) or 8 mg/kg BU, 180 mg/m2 FLU and 40 mg/kg ATG (n=38). Graft-versus-host disease (GVHD) prophylaxis consisted of CSA alone (n=32) or a combination with either MTX or MMF (n=51). The median age was 52 years. Graft failure occurred in two patients after BU/FLU and in three after BU/FLU/ATG (P=0.66). After conditioning with BU/FLU, platelet recovery was significantly faster (P=0.017), and less platelet (P<0.001) and red blood cell (P=0.002) support was needed. Incidences of acute GVHD grades II and IV were 46 and 49%, respectively. Limited chronic GVHD occurred more often after BU/FLU compared to BU/FLU/ATG (54 vs 23%, P=0.02). The overall survival, non-relapse and relapse mortality did not differ significantly. We conclude that in peripheral blood stem cell transplantation from HLA-identical siblings after reduced-intensity conditioning with BU and FLU, ATG has no major impact on the rate of graft rejection and acute GVHD, but it reduces the incidence of limited chronic GVHD.

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

Access options

Buy this article

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

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Slavin S, Nagler A, Naparstek E 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  Google Scholar 

  2. Eiermann TH, Lambrecht P, Zander AR . Monitoring anti-thymocyte globulin (ATG) in bone marrow recipients. Bone Marrow Transplant 1999; 23: 779–781.

    Article  CAS  Google Scholar 

  3. Zander AR, Zabelina T, Kroger N et al. Use of a five-agent GVHD prevention regimen in recipients of unrelated donor marrow. Bone Marrow Transplant 1999; 23: 889–893.

    Article  CAS  Google Scholar 

  4. Eiermann TH, Freitag S, Cortes-Dericks L et al. Jurkat cell-reactive anti-thymocyte globulin assessed ex vivo by flow cytometry persists three weeks in circulation. J Hematother Stem Cell Res 2001; 10: 385–390.

    Article  CAS  Google Scholar 

  5. Pihusch R, Holler E, Muhlbayer D et al. The impact of antithymocyte globulin on short-term toxicity after allogeneic stem cell transplantation. Bone Marrow Transplant 2002; 30: 347–354.

    Article  CAS  Google Scholar 

  6. Bacigalupo A, Lamparelli T, Bruzzi 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  Google Scholar 

  7. Kroger N, Zabelina T, Kruger W et al. Anti-thymocyte-globulin as part of the preparative regimen prevents graft failure and severe graft versus host disease (GvHD) in allogeneic stem cell transplantation from unrelated donors. Ann Hematol 2001; 80: 209–215.

    Article  CAS  Google Scholar 

  8. Kroger N, Zabelina T, Kruger W et al. In vivo T cell depletion with pretransplant anti-thymocyte globulin reduces graft-versus-host disease without increasing relapse in good risk myeloid leukemia patients after stem cell transplantation from matched related donors. Bone Marrow Transplant 2002; 29: 683–689.

    Article  CAS  Google Scholar 

  9. Remberger M, Storer B, Ringden O, Anasetti C . Association between pretransplant thymoglobulin and reduced non-relapse mortality rate after marrow transplantation from unrelated donors. Bone Marrow Transplant 2002; 29: 391–397.

    Article  CAS  Google Scholar 

  10. Finke J, Schmoor C, Lang H et al. Matched and mismatched allogeneic stem-cell transplantation from unrelated donors using combined graft-versus-host disease prophylaxis including rabbit anti-T lymphocyte globulin. J Clin Oncol 2003; 21: 506–513.

    Article  Google Scholar 

  11. Bornhäuser M, Thiede C, Schuler U et al. Dose-reduced conditioning for allogeneic blood stem cell transplantation: durable engraftment without antithymocyte globulin. Bone Marrow Transplant 2000; 26: 119–125.

    Article  Google Scholar 

  12. Thiede C, Florek M, Bornhauser M et al. Rapid quantification of mixed chimerism using multiplex amplification of short tandem repeat markers and fluorescence detection. Bone Marrow Transplant 1999; 23: 1055–1060.

    Article  CAS  Google Scholar 

  13. Elmaagacli AH, Beelen DW, Becks HW et al. Molecular studies of chimerism and minimal residual disease after allogeneic peripheral blood progenitor cell or bone marrow transplantation. Bone Marrow Transplant 1996; 18: 397–403.

    CAS  Google Scholar 

  14. Fehse B, Chukhlovin A, Kuhlcke K et al. Real-time quantitative Y chromosome-specific PCR (QYCS-PCR) for monitoring hematopoietic chimerism after sex-mismatched allogeneic stem cell transplantation. J Hematother Stem Cell Res 2001; 10: 419–425.

    Article  CAS  Google Scholar 

  15. Przepiorka D, Weisdorf D, Martin P et al. 1994 consensus conference on acute GVHD grading. Bone Marrow Transplant 1995; 15: 825–828.

    CAS  Google Scholar 

  16. Atkinson K, Horowitz MM, Gale RP et al. Consensus among bone marrow transplanters for diagnosis, grading and treatment of chronic graft-versus-host disease. Committee of the International Bone Marrow Transplant Registry. Bone Marrow Transplant 1989; 4: 247–254.

    CAS  Google Scholar 

  17. Or R, Shapira MY, Resnick I et al. Nonmyeloablative allogeneic stem cell transplantation for the treatment of chronic myeloid leukemia in first chronic phase. Blood 2003; 101: 441–445.

    Article  CAS  Google Scholar 

  18. Schleuning M, Gunther W, Tischer J et al. Dose-dependent effects of in vivo antithymocyte globulin during conditioning for allogeneic bone marrow transplantation from unrelated donors in patients with chronic phase CML. Bone Marrow Transplant 2003; 32: 243–250.

    Article  CAS  Google Scholar 

  19. Mohty M, Bay JO, Faucher C et al. Graft-versus-host disease following allogeneic HLA-identical sibling transplantation with anti-thymocyte globulin-based reduced intensity preparative regimen. Blood 2003; 102: 470–476.

    Article  CAS  Google Scholar 

  20. Duggan P, Booth K, Chaudhry A et al. Unrelated donor BMT recipients given pretransplant low-dose antithymocyte globulin have outcomes equivalent to matched sibling BMT: a matched pair analysis. Bone Marrow Transplant 2002; 30: 681–686.

    Article  CAS  Google Scholar 

  21. Russell JA, Chaudhry AM, Fibich C et al. Improved survival in adult matched sibling stem cell transplant recipients given pretransplant low-dose antithymocyte globulin: a matched pair analysis. Blood 2002; 100: 429 (abstr 1663).

    Google Scholar 

Download references

Acknowledgements

We thank Catrin Theuser, Silke Freund, Karin Davis and Dr Ludwig Kraut for data management. The study was supported by the Kompetenznetz ‘Akute und chronische Leukämien’.

Author information

Authors and Affiliations

Authors

Consortia

Corresponding author

Correspondence to W Siegert.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schetelig, J., Bornhäuser, M., Kiehl, M. et al. Reduced-intensity conditioning with busulfan and fludarabine with or without antithymocyte globulin in HLA-identical sibling transplantation – a retrospective analysis. Bone Marrow Transplant 33, 483–490 (2004). https://doi.org/10.1038/sj.bmt.1704384

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1704384

Keywords

This article is cited by

Search

Quick links