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.

  • Review
  • Published:

Risk-adapted procedures for HSCT from alternative donor in children with severe aplastic anaemia

Bone Marrow Transplantation volume 42, pages S97–S100 (2008)Cite this article

Abstract

The outcome of haematopoietic SCT (HSCT) from matched unrelated donors in children with severe aplastic anaemia (SAA) has improved significantly in the last decade and should be offered to all children who fail to respond to their first course of combined immunosuppressive therapy. High-resolution typing for HLA class I and II is mandatory for donor selection. In 10/10 or 9/10 alleles matched donors, a non-TBI conditioning based on fludarabine, CY and anti-thymocyte globulin is sufficient to allow for sustained engraftment when unmanipulated BM is used. Owing to increased rates of cGVHD after PBSC transplantation are reported in young patients, BM is the preferred stem cell source. HSCT from mismatched related and unrelated donors are still high-risk procedures. New techniques for graft manipulation such as CD3/CD19 depletion might improve engraftment and immune reconstitution. In T-cell depleted grafts, irradiation-based conditioning seems to be inevitable to reduce the high risk for rejection.

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

Similar content being viewed by others

References

  1. Führer M, Rampf U, Baumann I, Faldum A, Niemeyer C, Janka-Schaub G et al. Immunosuppressive therapy for aplastic anemia in children: a more severe disease predicts better survival. Blood 2005; 106: 2102–2104.

    Article  Google Scholar 

  2. Kojima S, Hibi S, Kosaka Y, Yamamoto M, Tsuchida M, Mugishima H et al. Immunosuppressive therapy using antithymocyte globulin, cyclosporine, and danazol with or without human granulocyte colony-stimulating factor in children with acquired aplastic anemia. Blood 2000; 96: 2049–2054.

    CAS  PubMed  Google Scholar 

  3. Locasciulli A, Oneto R, Bacigalupo A, Socie G, Korthof E, Bekassy A et al. Outcome of patients with acquired aplastic anemia given first line bone marrow transplantation or immunsuppressive treatment in the last decade: a report from the European Group for Blood and Marrow Transplantation. Haematologica 2007; 92: 11–18.

    Article  CAS  Google Scholar 

  4. Kosaka Y, Yagasaki H, Sano K, Kobayashi R, Ayukawa H, Kaneko T et al. Prospective multicenter trial comparing repeated immunosuppressive therapy with stem cell transplantation from an alternative donor as second-line treatment for children with severe and very severe aplastic anemia. Blood 2008; 111: 1054–1059.

    Article  CAS  Google Scholar 

  5. Bagby GC, Meyers G . Bone marrow failure as a risk factor for clonal evolution: prospects for leukemia prevention. Hematology AM Soc Hematol Educ Program 2007; 2007: 40–46.

    Article  Google Scholar 

  6. Kobayashi R, Yabe H, Hara J, Morimoto A, Tsuchida M, Mugishima H et al. Preceding immunosuppressive therapy with antithymocyte globulin and cyclosporine increases the incidence of graft rejection in children with aplastic anaemia who underwent allogeneic bone marrow transplantation from HLA-identical siblings. Br J Haematol 2006; 135: 693–696.

    Article  CAS  Google Scholar 

  7. Deeg HJ, Seidel K, Casper J, Anasetti C, Davies S, Gajewski JL et al. Marrow transplantation from unrelated donors for patients with severe aplastic anemia who have failed immunosuppressive therapy. Biol Blood Marrow Transplant 1999; 5: 243–252.

    Article  CAS  Google Scholar 

  8. Deeg HJ, Amylon MD, Harris RE, Collins R, Beatty PG, Feig S et al. Marrow transplants from unrelated donors for patients with aplastic anemia: minimum effective dose of total body irradiation. Biol Blood Marrow Transplant 2001; 7: 208–215.

    Article  CAS  Google Scholar 

  9. Kojima S, Matsuyama T, Kato S, Kigasawa H, Kobayashi R, Kikuta A et al. Outcome of 153 patients with severe aplastic anemia who received transplants from unrelated donors: the Japan Marrow Donor Program. Blood 2002; 100: 799–803.

    Article  CAS  Google Scholar 

  10. Viollier R, Socie G, Tichelli A, Bacigalupo A, Korthof ET, Marsh J et al. Recent improvement in outcome of unrelated donor transplantation for aplastic anemia. Bone Marrow Transplant 2008; 41: 45–50.

    Article  CAS  Google Scholar 

  11. Yagasaki H, Takahashi Y, Kudo K, Ohashi H, Hama A, Yamamoto T et al. Feasibility and results of bone marrow transplantation from an HLA-mismatched unrelated donor for children and young adults with acquired severe aplastic anemia. Int J Hematol 2007; 85: 437–442.

    Article  Google Scholar 

  12. Stern M, Passweg J, Locasciulli A, Socie G, Schrezenmeier H, Bekassy AN et al. Influence of donor/recipient sex matching on outcome of allogeneic hematopoietic stem cell transplantation for aplastic anemia. Transplantation 2006; 82: 218–226.

    Article  Google Scholar 

  13. Schrezenmeier H, Passweg JR, Marsh JCW, Bacigalupo A, Bredeson CN, Bullorsky E et al. Worse outcome and more chronic GVHD with peripheral blood progenitor cells than bone marrow in HLA-matched sibling donor transplants for young patients with severe acquired aplastic anemia. Blood 2007; 110: 1397–1400.

    Article  CAS  Google Scholar 

  14. Rubinstein P, Carrier C, Scaradavou A, Kurtzberg J, Adamson J, Migliaccio AR et al. Outcomes among 562 recipients of placental-blood transplants from unrelated donors. N Engl J Med 1998; 339: 1565–1577.

    Article  CAS  Google Scholar 

  15. Passweg JR, Socie G, Hinterberger W, Bacigalupo A, Biggs JC, Camitta BM et al. Bone marrow transplantation for severe aplastic anemia: has outcome improved? Blood 1997; 90: 858–864.

    CAS  PubMed  Google Scholar 

  16. Benesch M, Urban C, Sykora KW, Schwinger W, Zintl F, Lackner H et al. Transplantation of highly purified CD34+ progenitor cells from alternative donors in children with refractory severe aplastic anaemia. Br J Haematol 2004; 125: 58–63.

    Article  Google Scholar 

  17. Woodard P, Cunningham JM, Benaim E, Chen X, Hale G, Horowitz E et al. Effective donor lymphohematopoietic reconstitution after haploidentical CD34+-selected hematopoietic stem cell transplantation in children with refractory severe aplastic anemia. Bone Marrow Transplant 2004; 33: 411–418.

    Article  CAS  Google Scholar 

  18. Kojima S, Inaba A, Yoshimi A, Takahashi Y, Watanabe N, Kudo K et al. Unrelated donor marrow transplantation in children with severe aplastic anaemia using cyclophosphamide, anti-thymocyte globulin and total body irradiation. Br J Haematol 2001; 114: 706–711.

    Article  CAS  Google Scholar 

  19. Vassiliou GS, Webb DKH, Pamphilon D, Knapper S, Veys PA . Improved outcome of alternative donor bone marrow transplantation in children with severe aplastic anaemia using a conditioning regimen containing low-dose total body irradiation, cyclophosphamide and campath. Br J Haematol 2001; 114: 701–705.

    Article  CAS  Google Scholar 

  20. Chan KW, Li CK, Worth LL, Chik KW, Jeha S, Shing MK et al. A fludarabine-based conditioning regimen for severe aplastic anemia. Bone Marrow Transplant 2001; 27: 125–128.

    Article  CAS  Google Scholar 

  21. Bunin N, Aplenc R, Iannone R, Leahey A, Grupp S, Monos D et al. Unrelated donor bone marrow transplantation for children with severe aplastic anemia: minimal GvHD and durable engraftment with partial T cell depletion. Bone Marrow Transplant 2005; 35: 369–373.

    Article  CAS  Google Scholar 

  22. Bacigalupo A, Locatelli F, Lanino E, Marsh J, Socie G, Maury S et al. Fludarabine, cyclophosphamide and anti-thymocyte globulin for alternative donor transplants in acquired severe aplastic anemia: a report from the EBMT-SAA Working Party. Bone Marrow Transplant 2005; 36: 947–950.

    Article  CAS  Google Scholar 

  23. Eapen M, Ramsay NKC, Mertens AC, Robinson LL, DeFor T, Davies SM . Late outcomes after bone marrow transplant for aplastic anaemia. Br J Haematol 2000; 111: 754–760.

    CAS  PubMed  Google Scholar 

  24. Socie G, Henry-Amar M, Bacigalupo A, Hows J, Tichelli A, Ljungman P et al. Malignant tumors occurring after treatment of aplastic anemia. N Engl J Med 1993; 329: 1152–1157.

    Article  CAS  Google Scholar 

  25. Ades L, Mary J-Y, Robin M, Ferry C, Porcher R, Esperou H et al. Long-term outcome after bone marrow transplantation for severe aplastic anemia. Blood 2004; 103: 2490–2497.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

I want to thank Charlotte Niemeyer and her team of EWOG-MDS for their support.

Author information

Authors and Affiliations

  1. Department of Haematology, Oncology and Bone Marrow Transplantation, Dr von Haunersches Kinderspital, Ludwig-Maximilians University of Munich, Munich, Germany

    M Führer

Authors
  1. M Führer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M Führer.

Additional information

Conflict of interest

Monica Fuhrer has received lecture fees from an unnamed source. M Fuhrer is also negotiating with Genzyme to support an international study in immunosuppressive therapy in SAA in children.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Führer, M. Risk-adapted procedures for HSCT from alternative donor in children with severe aplastic anaemia. Bone Marrow Transplant 42 (Suppl 2), S97–S100 (2008). https://doi.org/10.1038/bmt.2008.293

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2008.293

Keywords

This article is cited by

Search

Advanced search

Quick links