Skip to main content
SpringerLink
Log in

Favorable outcome in children and adolescents with a high proportion of advanced phase disease using single/multiple autologous or matched/mismatched allogeneic stem cell transplantations

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

We determined the indication, outcome, and risk factors of single and multiple hematopoietic stem cell transplantation(s) (HSCT) in children and adolescents mostly with advanced disease. Forty-one out of 483 patients (8.5 %; median age 9 years) diagnosed at the University of Leipzig with hematological and oncological diseases required HSCT from 1999 to 2011. Patients had overall survival (OS) of 63 ± 10 and 63 ± 16 %, event-free survival (EFS) of 57 ± 10 and 42 ± 16 %, relapse incidence (RI) of 39 ± 10 and 44 ± 18 % and nonrelapse mortality (NRM) of 4 ± 4 and 13 ± 9 % at 10 years after one or more allogeneic and autologous HSCT, respectively. One patient in CR1 and five with advanced disease received two HSCT. Four of the six patients maintained/achieved CR for a median of 13 months. Three died of progression and one of NRM. Two patients had a third HSCT and one survived in CR +231 days after HSCT. Risk factors for OS and EFS were disease stage at HSCT and EBMT risk score. Center (pediatric or JACIE accredited pediatric/adult) was not a determinant for survival. Pediatric single and multiple HSCT are important curative approaches for high-risk malignant diseases with low NRM. Efforts to reduce high RI remain the major aim.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Schmid C, Schleuning M, Schwerdtfeger R, Hertenstein B, Mischak-Weissinger E et al (2006) Long-term survival in refractory acute myeloid leukemia after sequential treatment with chemotherapy and reduced-intensity conditioning for allogeneic stem cell transplantation. Blood 108:1092–1099

    Article  CAS  PubMed  Google Scholar 

  2. Woods WG, Neudorf S, Gold S, Sanders J, Buckley JD, Barnard DR et al (2001) Children’s Cancer Group. A comparison of allogeneic bone marrow transplantation, autologous bone marrow transplantation, and aggressive chemotherapy in children with acute myeloid leukemia in remission. Blood 97:56–62

    Article  CAS  PubMed  Google Scholar 

  3. Chakrabarti S, Childs R (2003) Allogeneic immune replacement as cancer immunotherapy. Expert Opin Biol Ther 3:1051–1060

    Article  PubMed  Google Scholar 

  4. Gooley TA, Chien JW, Pergam SA, Hingorani S, Sorror ML, Boeckh M et al (2010) Reduced mortality after allogeneic hematopoietic-cell transplantation. N Engl J Med 363:2091–2101

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Niewerth D, Creutzig U, Bierings MB, Kaspers GJ (2010) A review on allogeneic stem cell transplantation for newly diagnosed pediatric acute myeloid leukemia. Blood 116:2205–2214

    Article  CAS  PubMed  Google Scholar 

  6. Niederwieser D, Maris M, Shizuru JA, Petersdorf E, Hegenbart U, Sandmaier BM et al (2003) 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 and mycophenolate mofetil (MMF) can induce durable complete chimerism and sustained remissions in patients with hematological diseases. Blood 4:1620–1629

    Article  Google Scholar 

  7. Cornelissen JJ, Gratwohl A, Schlenk RF, Sierra J, Bornhäuser M, Juliusson G et al (2012) The European LeukemiaNet AML Working Party consensus statement on allogeneic HSCT for patients with AML in remission: an integrated-risk adapted approach. Nat Rev Clin Oncol 9:579–590

    Article  CAS  PubMed  Google Scholar 

  8. Advani AS, Hunger SP, Burnett AK (2009) Acute leukemia in adolescents and young adults. Semin Oncol 36:213–226

    Article  CAS  PubMed  Google Scholar 

  9. Kaspers GJ, Creutzig U (2005) Pediatric acute myeloid leukemia: international progress and future directions. Leukemia 19:2025–2029

    Article  CAS  PubMed  Google Scholar 

  10. Nussbaumer W, Schwaighofer H, Gratwohl A, Kilga S, Schönitzer D, Nachbaur D et al (1995) Transfusion of donor-type red cells as a single preparative treatment for bone marrow transplants with major ABO incompatibility. Transfusion 35:592–595

    Article  CAS  PubMed  Google Scholar 

  11. Gratwohl A (2012) The EBMT risk score. Bone Marrow Transplant 47:749–756

    Article  CAS  PubMed  Google Scholar 

  12. Cornelissen JJ, van Putten WL, Verdonck LF, Theobald M, Jacky E, Daenen SM et al (2007) Results of a HOVON/SAKK donor versus no-donor analysis of myeloablative HLA-identical sibling stem cell transplantation in first remission acute myeloid leukemia in young and middle-aged adults: benefits for whom? Blood 109:3658–3666

    Article  CAS  PubMed  Google Scholar 

  13. Passweg JR, Baldomero H, Peters C, Gaspar HB, Cesaro S, Dreger P et al (2014) Hematopoietic SCT in Europe: data and trends in 2012 with special consideration of pediatric transplantation. Bone Marrow Transplant 49:744–750

    Article  PubMed Central  PubMed  Google Scholar 

  14. Wachowiak J, Labopin M, Miano M, Chybicka A, Stary J, Sterba J et al (2008) Haematopoietic stem cell transplantation in children in eastern European countries EBMT Paediatric Working Party. 1985-2004: development, recent activity and role of the EBMT/ESH Outreach Programme. Bone Marrow Transplant 41(Suppl 2):S112–S117

    Article  PubMed  Google Scholar 

  15. Gratwohl A, Baldomero H, Gratwohl M, Aljurf M, Bouzas LF, Horowitz M et al (2013) For the Worldwide Network of Blood and Marrow Transplantation (WBMT). Quantitative and qualitative differences in use and trends of hematopoietic stem cell transplantation: a Global Observational Study. Haematologica 98:1282–1290

    Article  PubMed Central  PubMed  Google Scholar 

  16. Gratwohl A, Baldomero H, Aljurf M, Pasquini MC, Bouzas LF, Yoshimi A et al (2010) For the Worldwide Network of Blood and Marrow Transplantation. Hematopoietic stem cell transplantation: a global perspective. JAMA 303:1617–1624

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Fagioli F, Quarello P, Zecca M, Lanino E, Rognoni C, Balduzzi A et al (2013) Hematopoietic stem cell transplantation for children with high-risk acute lymphoblastic leukemia in first complete remission: a report from the AIEOP registry. Haematologica 98:1273–1281

    Article  PubMed Central  PubMed  Google Scholar 

  18. Sedlacek P, Formankova R, Mejstrikova E, Keslova P, Hubacek P, Dobrovolna M et al (2008) Allogeneic stem cell transplantation in children with leukemia using human leukocyte antigen-mismatched unrelated donors. Pediatr Transplant 12:24–31

    Article  PubMed  Google Scholar 

  19. Locatelli F, Masetti R, Rondelli R, Zecca M, Fagioli F, Rovelli A et al (2014) Outcome of children with high-risk acute myeloid leukemia given autologous or allogeneic hematopoietic cell transplantation in the aieop AML-2002/01 study. Bone Marrow Transplant 50:181–188

    Article  PubMed  Google Scholar 

  20. Bajwa R, Schechter T, Soni S, Gassas A, Doyle J, Sisler I et al (2013) Outcome of children who experience disease relapse following allogeneic hematopoietic SCT for hematologic malignancies. Bone Marrow Transplant 48:661–665

    Article  CAS  PubMed  Google Scholar 

  21. Oda M, Isoyama K, Ito E, Inoue M, Tsuchida M, Kigasawa H et al (2009) Survival after cord blood transplantation from unrelated donor as a second hematopoietic stem cell transplantation for recurrent pediatric acute myeloid leukemia. Int J Hematol 89:374–382

    Article  CAS  PubMed  Google Scholar 

  22. Weber-Mzell D, Urban C, Benesch M, Rojacher T, Zois B, Höfler G et al (2007) Durable remission following a third allogeneic stem cell transplantation in a patient with repeatedly relapsing SAA. The importance of stroma cells for sustained engraftment? Pediatr Transplant 11:332–335

    Article  PubMed  Google Scholar 

  23. Bacigalupo A1, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V, Apperley J, Slavin S, Pasquini M, Sandmaier BM, Barrett J, Blaise D, Lowski R, Horowitz M (2009) Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant 15(12):1628--1633

Download references

Acknowledgments

We thank the transplantation teams of the participating hospitals.

Author information

Author notes

  1. C. Niederwieser

    Present address: The Ohio State University, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute C933 James Cancer Hospital, 460 West 10th Avenue, Columbus, OH, 43210, USA

Authors and Affiliations

  1. Department of Pediatric Hematology/Oncology/Hemostaseology, Children’s Hospital, University of Leipzig, Liebigstrasse 20a, D-04103, Leipzig, Germany

    C. Niederwieser, S. Starke, L. Fischer & H. Christiansen

  2. Department of Hematology and Oncology, University of Leipzig, Leipzig, Germany

    R. Krahl, H-K. Al-Ali, M. Cross, A-K. Eisfeld, S. Heyn, V. Vucinic, G-N. Franke, T. Lange, W. Pönisch & G. Behre

  3. Section for Hematology and Oncology, Department of Pediatrics, Jena University Hospital, Jena, Germany

    J. Beck & B. Gruhn

  4. Pediatric BMT Unit, Charité, Universitätsmedizin Berlin, Berlin, Germany

    W. Ebell

  5. Department of Pediatrics, University Hospital, Halle (Saale), Germany

    D. Körholz

  6. Department of Pediatric Hematology and Oncology, Justus Liebig University, Giessen, Germany

    W. Wößmann

  7. Stem Cell Transplantation and Immunology, Klinik für Kinder und Jugendmedizin, Frankfurt am Main, Germany

    P. Bader

  8. Hematology / Oncology, University Children’s Hospital Tuebingen, Tuebingen, Germany

    P. Lang

Authors
  1. C. Niederwieser
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Starke
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. Fischer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. Krahl
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. Beck
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. B. Gruhn
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. W. Ebell
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. D. Körholz
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. W. Wößmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. P. Bader
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. P. Lang
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. H-K. Al-Ali
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. M. Cross
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. A-K. Eisfeld
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. S. Heyn
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. V. Vucinic
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. G-N. Franke
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. T. Lange
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. W. Pönisch
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. G. Behre
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. H. Christiansen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C. Niederwieser.

Ethics declarations

Conflict of interest

All authors declare no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants or legal representatives included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Niederwieser, C., Starke, S., Fischer, L. et al. Favorable outcome in children and adolescents with a high proportion of advanced phase disease using single/multiple autologous or matched/mismatched allogeneic stem cell transplantations. Ann Hematol 95, 473–481 (2016). https://doi.org/10.1007/s00277-015-2569-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-015-2569-7

Keywords

Search

Navigation