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

Relapse, not regimen-related toxicity, was the major cause of treatment failure in 11 children with Down syndrome undergoing haematopoietic stem cell transplantation for acute leukaemia

Bone Marrow Transplantation volume 40, pages 945–949 (2007)Cite this article

Abstract

We report a retrospective analysis of 11 children with Down syndrome (DS) treated by SCT in eight German/Austrian SCT centres. Indications for transplantation were acute lymphoblastic leukaemia (N=8) and acute myeloid leukaemia (N=3). A reduced intensity conditioning (RIC) containing 2 Gy TBI was given to two patients, another five received a myeloablative regimen with 12 Gy TBI. Treosulphan or busulphan was used in the remaining four children. Four of eleven (36%) patients are alive. All of them were treated with a myeloablative regimen. One of the four surviving children relapsed 9 months after SCT and is currently receiving palliative outpatient treatment. The main cause of death was relapse (5/11). Two children died of regimen-related toxicity (RRT), one from severe exfoliative dermatitis and multiorgan failure after a treosulphan-containing regimen, the other from GvHD-related infections after RIC. Acute GvHD of the skin was observed in 10 of 10 evaluable patients, and chronic GvHD in 4 of 8. Our data show that DS patients can tolerate commonly used, fully myeloablative preparative regimens. The major cause of death is relapse rather than RRT resulting in an event-free survival of 18% and over all survival of 36%.

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. Lange B . The management of neoplastic disorders of haematopoiesis in children with Down's syndrome. Br J Haematol 2000; 110: 512–524.

    Article  CAS  PubMed  Google Scholar 

  2. Krivit W, Good RA . The simultaneous occurrence of leukemia, mongolism; report of four cases. AMA J Dis Child 1956; 91: 218–222.

    Article  CAS  PubMed  Google Scholar 

  3. Dordelmann M, Schrappe M, Reiter A, Zimmermann M, Graf N, Schott G et al. Down's syndrome in childhood acute lymphoblastic leukemia: clinical characteristics, treatment outcome in four consecutive BFM trials. Berlin-Frankfurt-Munster Group. Leukemia 1998; 12: 645–651.

    Article  CAS  PubMed  Google Scholar 

  4. Whitlock JA, Sather HN, Gaynon P, Robison LL, Wells RJ, Trigg M et al. Clinical characteristics, outcome of children with Down syndrome, acute lymphoblastic leukemia: a Children's Cancer Group study. Blood 2005; 106: 4043–4049.

    Article  CAS  PubMed  Google Scholar 

  5. Lange BJ, Kobrinsky N, Barnard DR, Arthur DC, Buckley JD, Howells WB et al. Distinctive demography, biology, outcome of acute myeloid leukemia, myelodysplastic syndrome in children with Down syndrome: Children's Cancer Group Studies 2861, 2891. Blood 1998; 91: 608–615.

    CAS  PubMed  Google Scholar 

  6. Creutzig U, Ritter J, Vormoor J, Ludwig WD, Niemeyer C, Reinisch I et al. Myelodysplasia, acute myelogenous leukemia in Down's syndrome. A report of 40 children of the AML-BFM Study Group. Leukemia 1996; 10: 1677–1686.

    CAS  PubMed  Google Scholar 

  7. Levitt GA, Stiller CA, Chessells JM . Prognosis of Down's syndrome with acute leukaemia. Arch Dis Child 1990; 65: 212–216.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Ravindranath Y, Abella E, Krischer JP, Wiley J, Inoue S, Harris M et al. Acute myeloid leukemia (AML) in Down's syndrome is highly responsive to chemotherapy: experience on Pediatric Oncology Group AML Study 8498. Blood 1992; 80: 2210–2214.

    CAS  PubMed  Google Scholar 

  9. Renson Jr EB, Forde MD . Bone marrow transplantation for acute leukemia and Down syndrome: report of a successful case and results of a national survey. J Pediatr 1989; 114: 69–72.

    Article  Google Scholar 

  10. Rubin CM, O'Leary M, Koch PA, Nesbit Jr ME . Bone marrow transplantation for children with acute leukemia and Down syndrome. Pediatrics 1986; 78: 688–691.

    CAS  PubMed  Google Scholar 

  11. Rubin CM, Mick R, Johnson FL . Bone marrow transplantation for the treatment of haematological disorders in Down's syndrome: toxicity and outcome. Bone Marrow Transplant 1996; 18: 533–540.

    CAS  PubMed  Google Scholar 

  12. Goleta-Dy A, Dalla Pozza L, Shaw PJ, Stevens MM . Acute myeloid leukaemia in patients with trisomy 21 (Down syndrome) treated by bone marrow transplantation. J Paediatr Child Health 1994; 30: 275–277.

    Article  CAS  PubMed  Google Scholar 

  13. Pawlowska AB, Davies SM, Orchard PJ, Wagner JE, Ramsay NK . Unrelated donor bone marrow transplantation for acute leukemia in patients with Down's syndrome. Bone Marrow Transplant 1996; 18: 453–455.

    CAS  PubMed  Google Scholar 

  14. Hegenbart U, Niederwieser D, Sandmaier BM, Maris MB, Shizuru JA, Greinix H et al. Treatment for acute myelogenous leukemia by low-dose, total-body, irradiation-based conditioning and hematopoietic cell transplantation from related and unrelated donors. J Clin Oncol 2006; 24: 444–453.

    Article  CAS  PubMed  Google Scholar 

  15. Locatelli F, Uderzo C, Dini G, Zecca M, Arcese W, Messina C et al. Graft-versus-host disease in children: the AIEOP-BMT Group experience with cyclosporin A. Bone Marrow Transplant 1993; 12: 627–633.

    CAS  PubMed  Google Scholar 

  16. Kondo M, Kojima S, Horibe K, Kato K, Matsuyama T . Risk factors for chronic graft-versus-host disease after allogeneic stem cell transplantation in children. Bone Marrow Transplant 2001; 27: 727–730.

    Article  CAS  PubMed  Google Scholar 

  17. Zecca M, Prete A, Rondelli R, Lanino E, Balduzzi A, Messina C et al. Chronic graft-versus-host disease in children: incidence, risk factors, and impact on outcome. Blood 2002; 100: 1192–1200.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Paediatric Haematology and Oncology, Hannover Medical School, Hannover, Germany

    B Meissner, B Maecker, K W Sykora, K Welte & M Sauer

  2. Department of Paediatric Haematology and Oncology, Dr von Haunersches Kinderspital, University of Munich, Munich, Germany

    A Borkhardt & F R Schuster

  3. Clinic of Paediatric Haematology, Oncology and Clinical Immunology, HHU Duesseldorf, Duesseldorf, Germany

    A Borkhardt, D Dilloo & F R Schuster

  4. Department of Paediatric Haematology and Oncology, Friedrich-Schiller-University Jena, Jena, Germany

    D Fuchs & F Zintl

  5. Department of Paediatrics, University of Ulm, Ulm, Germany

    W Friedrich

  6. Department of Paediatric Haematology and Oncology, University Children's Hospital, Eberhard Karls University, Tuebingen, Germany

    R Handgretinger

  7. Department of Paediatric Haematology and Oncology, St Anna Children's Hospital, Vienna, Austria

    C Peters

  8. Department of Paediatrics, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany

    A Schrauder

  9. Department of Paediatric Haematology and Oncology, University Children's Hospital, Muenster, Germany

    J Vormoor

Authors
  1. B Meissner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A Borkhardt
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D Dilloo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D Fuchs
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. W Friedrich
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. R Handgretinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. C Peters
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A Schrauder
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. F R Schuster
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. J Vormoor
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. B Maecker
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. K W Sykora
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. F Zintl
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. K Welte
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. M Sauer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M Sauer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Meissner, B., Borkhardt, A., Dilloo, D. et al. Relapse, not regimen-related toxicity, was the major cause of treatment failure in 11 children with Down syndrome undergoing haematopoietic stem cell transplantation for acute leukaemia. Bone Marrow Transplant 40, 945–949 (2007). https://doi.org/10.1038/sj.bmt.1705844

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1705844

Keywords

This article is cited by

Search

Advanced search

Quick links