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:

Conditioning

Second allogeneic transplantation for relapse of malignant disease: retrospective analysis of outcome and predictive factors by the EBMT

Bone Marrow Transplantation volume 50, pages 1542–1550 (2015)Cite this article

Subjects

Abstract

In patients treated with allogeneic stem cell transplantation (SCT) for malignant disease who suffer from a relapse after the transplantation, the role of second allogeneic SCT is often uncertain. In a retrospective analysis, 2632 second allogeneic transplantations carried out for a relapse after the first transplantation were analyzed to define indications and identify predictive factors. Fifteen percent of the patients remained relapse-free until 5 years after the second SCT. Patients with CML had a better survival than patients with other diseases. In a multivariate analysis, factors associated with better survival were low disease burden, longer remission duration after the first transplantation, longer interval between the transplantations, younger age, absence of grade II–IV acute GvHD or chronic GvHD after the first transplantation, and later year of transplantation. The European Society for Blood and Marrow Transplantation risk score predicted the outcome. Using the same donor as in the first transplantation vs another donor had no predictive value for survival. Sibling donor was a favorable predictive factor. In conclusion, second allogeneic SCT offers a reasonable option especially for young patients with a long remission after the first transplantation and a low disease burden. The present findings do not support the usefulness of changing the donor for the second transplantation.

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

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. Mielcarek M, Storer BE, Flowers MED, Storb R, Sandmaier BM, Martin PJ . Outcomes among patients with recurrent high-risk malignancies after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2007; 13: 1160–1168.

    Article  Google Scholar 

  2. Oran B, de Lima M . Prevention and treatment of acute myeloid leukemia relapse after allogeneic stem cell transplantation. Curr Opin Hematol 2011; 18: 388–394.

    Article  CAS  Google Scholar 

  3. Kolb HJ . Donor leukocyte transfusions for treatment of leukemic relapse after bone marrow transplantation. EBMT Immunology and Chronic Leukemia Working Parties. Vox Sanguinis 1998; 74: 321–329.

    Article  CAS  Google Scholar 

  4. http://www.ebmt.org/Contents/Data-Management/Registrystructure/MED-ABdatacollectionforms/Pages/MED-AB-data-collection-forms.aspx.

  5. Michallet M, Tanguy ML, Socie G, Thiebaut A, Belhabri A, Milpied N et al. Second allogeneic haematopoietic stem cell transplantation in relapsed acute and chronic leukaemias for patients who underwent a first allogeneic bone marrow transplantation: a survey of the Société Francaise de Greffe de Moelle (SFGM). Br J Haematol 2000; 108: 400–407.

    Article  CAS  Google Scholar 

  6. Bosi A, Laszlo D, Labopin M, Reiffers J, Michallet M, Gluckman E et al. for the Acute Leukemia Working Party of the European Blood and Marrow Transplant Group. Second allogeneic bone marrow transplantation in acute leukemia: results of a survey by the European Cooperative Group for Blood and Marrow Transplantation. J Clin Oncol 2001; 19: 3675–3684.

    Article  CAS  Google Scholar 

  7. Eapen M, Giralt SA, Horowitz MM, Klein JP, Wagner JE, Zhang MJ et al. Second transplant for acute and chronic leukemia relapsing after first HLA-identical sibling transplant. Bone Marrow Transplant 2004; 34: 721–727.

    Article  CAS  Google Scholar 

  8. Arfons LM, Tomblyn M, Rocha V, Lazarus HM . Second hematopoietic stem cell transplantation in myeloid malignancies. Curr Opin Hematol 2009; 16: 112–123.

    Article  Google Scholar 

  9. Barrett AJ, Locatelli F, Treleaven JG, Gratwohl A, Szydlo R, Zwaan FE . Second transplants for leukaemic relapse after bone marrow transplantation: high early mortality but favourable effect of chronic GVHD on continued remission. A report by the EBMT Leukaemia Working Party. Br J Haematol 1991; 79: 567–574.

    Article  CAS  Google Scholar 

  10. Hosing C, Saliba RM, Shahjahan M, Estey EH, Couriel D, Giralt S et al. Disease burden may identify patients more likely to benefit from second allogeneic hematopoietic stem cell transplantation to treat relapsed acute myelogenous leukemia. Bone Marrow Transplant 2005; 36: 157–162.

    Article  CAS  Google Scholar 

  11. Kishi K, Takahashi S, Gondo H, Shiobara S, Kanamaru A, Kato S et al. Second allogeneic bone marrow transplantation for post-transplant leukemia relapse: results of a survey of 66 cases in 24 Japanese institutes. Bone Marrow Transplant 1997; 19: 461–466.

    Article  CAS  Google Scholar 

  12. Shaw BE, Mufti GJ, Mackinnon S, Cavenagh JD, Pearce RM, Towlson KE et al. Outcome of second allogeneic transplants using reduced-intensity conditioning following relapse of haematological malignancy after an initial allogeneic transplant. Bone Marrow Transplant 2008; 42: 783–789.

    Article  CAS  Google Scholar 

  13. Christopeit M, Kuss O, Finke J, Bacher U, Beelen DW, Bornhauser M et al. Second allograft for hematologic relapse of acute leukemia after first allogeneic stem-cell transplantation from related and unrelated donors: the role of donor change. J Clin Oncol 2013; 31: 3259–3271.

    Article  Google Scholar 

  14. Christopoulos P, Schmoor C, Waterhouse M, Marks R, Wasch R, Bertz H et al. Reduced-intensity conditioning with fludarabine and thiotepa for second allogeneic transplantation of relapsed patients with AML. Bone Marrow Transplant 2013; 48: 901–907.

    Article  CAS  Google Scholar 

  15. Locatelli F . The role of repeat transplantation of haemopoietic stem cells and adoptive immunotherapy in treatment of leukaemia relapsing following allogeneic transplantation. Br J Haematol 1998; 102: 633–638.

    Article  CAS  Google Scholar 

  16. Savani BN, Mielke S, Reddy N, Goodman S, Jagasia M, Rezvani K . Management of relapse after allo-SCT for AML and the role of second transplantation. Bone Marrow Transplant 2009; 44: 769–777.

    Article  CAS  Google Scholar 

  17. Tomonari A, Iseki T, Ooi J, Nagayama H, Sato H, Takahashi T et al. Second allogeneic hematopoietic stem cell transplantation for leukemia relapse after first allogeneic transplantation: outcome of 16 patients in a single institution. Int J Hematol 2002; 75: 318–323.

    Article  Google Scholar 

  18. Döhner H, Estey EH, Amadori S, Appelbaum FR, Buchner T, Burnett AK et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 2010; 115: 453–474.

    Article  Google Scholar 

  19. Gratwohl A, Stern M, Brand R, Apperley J, Baldomero H, de Witte T et al. for the European Group for Blood and Marrow Transplantation and the European Leukemia Net. Risk score for outcome after allogeneic hematopoietic stem cell transplantation: a retrospective analysis. Cancer 2009; 115: 4715–4726.

    Article  Google Scholar 

  20. Gratwohl A, Hermans J, Goldman JM, Arcese W, Carreras E, Devergie A et al. for the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Risk assessment for patients with chronic myeloid leukaemia before allogeneic blood or marrow transplantation. Lancet 1998; 352: 1087–1092.

    Article  CAS  Google Scholar 

  21. Rezvani K, Kanfer EJ, Marin D, Gabriel I, Rahemtulla A, Taylor A et al. EBMT risk score predicts outcome of allogeneic hematopoietic stem cell transplantation in patients who have failed a previous transplant procedure. Biol Blood Marrow Transplant 2012; 18: 235–240.

    Article  Google Scholar 

  22. Guardiola P, Kuentz M, Garban F, Blaise D, Reiffers J, Attal M et al. Second early allogeneic stem cell transplantations for graft failure in acute leukaemia, chronic myeloid leukaemia and aplastic anemia. Br J Haematol 2000; 111: 292–302.

    Article  CAS  Google Scholar 

  23. Duus JE, Stiff PJ, Choi J, Parthasarathy M, Rodriguez T, Toor AA . Second allografts for relapsed hematologic malignancies: feasibility of using a different donor. Bone Marrow Transplant 2005; 35: 261–264.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Author contributions

TR, DN, TdW and AG designed the study; AvB, LdW, TR, MM, PD, RD, CP, LG, SS and NK collected and assembled the data; LdW, RB, AvB and TR analyzed and interpreted the data; TR, DN, TdW, AG, AvB and LdW wrote the manuscript; MM, PD, RD, CP, LG, SS and NK critically reviewed the manuscript; all authors approved the final manuscript.

Author information

Authors and Affiliations

  1. Comprehensive Cancer Center, Helsinki University Hospital, Helsinki, Finland

    T Ruutu

  2. Department of Medical Statistics and Bioinformatics, Leiden University Medical Center/EBMT Statistical Unit, Leiden, The Netherlands

    L C de Wreede & R Brand

  3. Department of Medical Statistics and Bioinformatics, EBMT Data Office Leiden, Leiden University Medical Center, Leiden, The Netherlands

    A van Biezen

  4. Hôpital Saint Antoine, Service d’Hématologie Clinique et de Thérapie Cellulaire; Université Pierre et Marie Curie; INSERM,

    M Mohty & L Garderet

  5. Université Pierre et Marie Curie, Paris, France

    M Mohty & L Garderet

  6. Department of Medicine V, University of Heidelberg, Heidelberg, Germany

    P Dreger

  7. Institut Català d’Oncologia, L’Hospitalet de Llobregat, Barcelona, Spain

    R Duarte

  8. Department of Pediatrics, Stem Cell Transplantation Unit, St Anna Children's Hospital, Vienna, Austria

    C Peters

  9. Medizinische Klinik und Poliklinik V, University of Heidelberg, Heidelberg, Germany

    S Schönland

  10. Hematology, Medical Faculty, University of Basel, Basel, Switzerland,

    A Gratwohl

  11. Department of Hematology/Oncology and Hemostasiology, University of Leipzig, Leipzig, Germany

    D Niederwieser

  12. Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands

    T de Witte

  13. Department of Stem Cell Transplantation, University Cancer Centre Hamburg, Hamburg, Germany

    N Kröger

Authors
  1. T Ruutu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L C de Wreede
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A van Biezen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R Brand
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M Mohty
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. P Dreger
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. R Duarte
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. C Peters
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. L Garderet
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. S Schönland
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. A Gratwohl
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. D Niederwieser
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. T de Witte
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. N Kröger
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

for the European Society for Blood and Marrow Transplantation (EBMT)

Corresponding author

Correspondence to T Ruutu.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on Bone Marrow Transplantation website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ruutu, T., de Wreede, L., van Biezen, A. et al. Second allogeneic transplantation for relapse of malignant disease: retrospective analysis of outcome and predictive factors by the EBMT. Bone Marrow Transplant 50, 1542–1550 (2015). https://doi.org/10.1038/bmt.2015.186

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2015.186

This article is cited by

Search

Advanced search

Quick links