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:

Pediatric Transplants

Nonmyeloablative stem cell transplantation for nonmalignant diseases in children with severe organ dysfunction

Bone Marrow Transplantation volume 38, pages 665–669 (2006)Cite this article

Abstract

Allogeneic stem cell transplantation (SCT) can cure several nonmalignant diseases in children. However, patients frequently have significant morbidity before transplantation and there is a high transplant-related mortality. Nonmyeloablative SCT might achieve the same goals but with less toxicity. Six pediatric patients with nonmalignant diseases underwent nonmyeloablative SCT from different stem cell sources. All patients were conditioned with fludarabine/melphalan with additional anti-thymocyte globulin for haploidentical grafts and prophylaxis for graft-versus-host disease (GVHD) consisting of tacrolimus and methotrexate with additional prednisolone for haploidentical grafts. Hematopoietic stem cells were neither T-cell depleted nor purged. All patients had severe organ dysfunction that precluded transplantation with conventional conditioning. Five of the six are alive and in complete disease resolution at a median of 19 months (range, 7–53 months) after SCT. One patient died of bacteremia before engraftment. Three patients achieved complete donor chimerism. Two patients remained stable mixed chimerism. Short-term toxicities were minimal. Acute and chronic GVHD were not seen. In summary, the fludarabine-based nonmyeloablative regimen followed by SCT provides a good approach for children with nonmalignant diseases. Even patients with severe organ dysfunctions had adequate engraftment with acceptable toxicities.

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. Giralt S, Estey E, Albitar M, van Besien K, Rondon G, Anderlini P et al. Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. Blood 1997; 89: 4531–4536.

    CAS  PubMed  Google Scholar 

  2. Niederwieser D, Maris M, Shizuru JA, Petersdorf E, Hegenbart U, Sandmaier BM et al. Low-dose total body irradiation (TBI) and fludarabine followed by hematopoietic cell transplantation (HCT) from HLA-matched or mismatched unrelated donors and postgrafting immunosuppression with cyclosporine mycophenolate mofetil (MMF) can induce durable complete chimerism and sustained remissions in patients with hematological diseases. Blood 2003; 101: 1620–1629.

    Article  CAS  PubMed  Google Scholar 

  3. Fischer A, Friedrich W, Fasth A, Blanche S, Deist FL, Girault D et al. Reduction of graft failure by monoclonal antibody (anti-LFA-1 CD11a) after HLA nonidentical bone marrow transplantation in children with immunodeficiencies, osteopetrosis, and Fanconi’s anemia: a European group for immunodeficiency/European Group for Bone Marrow Transplantation Report. Blood 1991; 77: 249–256.

    CAS  PubMed  Google Scholar 

  4. Antoine C, Müller S, Cant A, Cavazzana-Calvo M, Veys P, Vossen J et al. Long-term survival and transplantation of haematopoietic stem cells for immunodeficiencies: report of European experience 1968–99. Lancet 2003; 361: 553–560.

    Article  PubMed  Google Scholar 

  5. Jacobsohn DA, Emerick KM, Scholl P, Melin-Aldana H, O'Gorman M, Duerst R et al. Nonmyeloablative hematopoietic stem cell transplant for X-linked hyper-immunoglobulin M syndrome with cholangiopathy. Pediatrics 2004; 113: 122–127.

    Article  Google Scholar 

  6. Horwitz ME, Barret AJ, Brown MR, Carter CS, Childs R, Gallin JI et al. Treatment of chronic granulomatous disease with nonmyeloablative conditioning and a T-cell-depleted hematopoietic allograft. N Engl J Med 2001; 344: 881–888.

    Article  CAS  PubMed  Google Scholar 

  7. 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 

  8. Amrolia P, Gaspar HB, Hassan A, Webb D, Jones A, Sturt N et al. Nonmyeloablative stem cell transplantation for congenital immunodeficiencies. Blood 2000; 96: 1239–1246.

    CAS  PubMed  Google Scholar 

  9. Ratanatharathorn V, Nash RA, Przepiorka D, Devine SM, Klein JL, Weisdolf D et al. Phase III study comparing methotrexate and tacrolimus (prograf, FK506) with methotrexate and cyclosporine for graft-versus-host disease prophylaxis after HLA-identical sibling bone marrow transplantation. Blood 1998; 92: 2303–2314.

    CAS  PubMed  Google Scholar 

  10. Nash RA, Antin JH, Karanes C, Fay JW, Avalos BR, Yeager AM et al. Phase 3 study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors. Blood 2000; 96: 2062–2068.

    CAS  PubMed  Google Scholar 

  11. Uberti JP, Ayash L, Braun T, Reynolds C, Silver S, Ratanatharathorn V . Tacrolimus as monotherapy or combined with minidose methotrexate for graft-versus-host disease prophylaxis after allogeneic peripheral blood stem cell transplantation: long-term outcomes. Bone Marrow Transplant 2004; 34: 425–431.

    Article  CAS  PubMed  Google Scholar 

  12. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J et al. Report of the 1994 consensus conference on acute GVHD grading. Bone Marrow Transplant 1995; 15: 825–828.

    CAS  PubMed  Google Scholar 

  13. Peters C, Shapiro EG, Anderson J, Anderson J, Henslee-Downey PJ, Klemperer MR et al. Hurler syndrome: II. Outcome of HLA-genotypically identical sibling and HLA-haploidentical related donor bone marrow transplantation in fifty-four children. Blood 1998; 91: 2601–2608.

    CAS  PubMed  Google Scholar 

  14. Rao K, Amrolia PJ, Jones A, Jones A, Cale CM, Naik P et al. Improved survival after unrelated donor bone marrow transplantation in children with primary immunodeficiency using a reduced-intensity conditioning regimen. Blood 2005; 105: 879–885.

    Article  CAS  PubMed  Google Scholar 

  15. Baker KS, Wagner JE . Novel conditioning regimens and nonmyeloablative stem cell transplants. Curr Opin Pediatr 2002; 14: 17–22.

    Article  PubMed  Google Scholar 

  16. Baker JN, Weisdorf DJ, Defor TE, Blazar BR, Miller JS, Wagner JE . Rapid and complete donor chimerism in adult recipients of unrelated donor umbilical cord blood transplantation after reduced-intensity conditioning. Blood 2003; 102: 1915–1919.

    Article  Google Scholar 

  17. Lowsky R, Takahashi T, Liu YP, Dejbakhsh-Jones S, Grumet FC, Shizuru JA et al. Prospective conditioning for acute graft-versus-host disease. N Engl J Med 2005; 353: 1321–1331.

    Article  CAS  PubMed  Google Scholar 

  18. Mielcarek M, Martin PJ, Leisenring W, Flowers MED, Maloney DG, Sandmaier BM et al. Graft-versus-host disease after nonmyeloablative versus conventional hematopoietic stem cell transplantation. Blood 2003; 102: 756–762.

    Article  CAS  PubMed  Google Scholar 

  19. Crawley C, Szydlo R, Lalancette M, Bacigalupo A, Lange A, Brune M et al. Outcomes of reduced-intensity transplantation for chronic myeloid leukemia: an analysis of prognostic factors from the Chronic Leukemia Working Party of the EBMT. Blood 2005; 106: 2969–2976.

    Article  CAS  PubMed  Google Scholar 

  20. 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 

Download references

Acknowledgements

This study was supported partially by grants from the Fukushima Society for the Promotion of Medicine.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Fukushima Medical University School of Medicine, Fukushima, Japan

    A Kikuta, M Ito, K Mochizuki, M Akaihata, K Nemoto & H Sano

  2. Division of Blood Transfusion and Transplantation Immunology, Fukushima Medical University School of Medicine, Fukushima, Japan

    H Ohto

Authors
  1. A Kikuta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M Ito
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K Mochizuki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M Akaihata
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K Nemoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. H Sano
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. H Ohto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A Kikuta.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kikuta, A., Ito, M., Mochizuki, K. et al. Nonmyeloablative stem cell transplantation for nonmalignant diseases in children with severe organ dysfunction. Bone Marrow Transplant 38, 665–669 (2006). https://doi.org/10.1038/sj.bmt.1705511

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1705511

Keywords

This article is cited by

Search

Advanced search

Quick links