Skip to main content

Advertisement

SpringerLink
Log in

High incidence of chronic graft-versus-host disease after myeloablative allogeneic stem cell transplantation for chronic lymphocytic leukemia in Sweden: graft-versus-leukemia effect protects against relapse

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a potentially curative treatment option for eligible patients with chronic lymphocytic leukemia (CLL). However, it is known that cure of CLL is only possible if a graft-versus-leukemia effect is present. Between 1994 and 2007, 48 adults underwent allo-SCT for poor-risk CLL in Sweden. Of these, ten (21 %) patients aged 24–53 years (median: 46 years) received myeloablative conditioning (MAC), based on TBI and cyclophosphamide. All MAC patients had refractory, poorly controlled CLL before allo-SCT (partial remission in 9/10 patients and progressive disease in one). The cumulative incidence of acute graft-versus-host disease (GVHD) grades II–IV was 30 %. Nine patients developed chronic GVHD; extensive in four. Rates of nonrelapse mortality at 1, 3 and 10 years were 0, 10 and 20 %, respectively. Two patients relapsed 36 and 53 months after transplantation. Six patients were still alive after a median follow-up time of 11.5 years (range 5.9–13.7). The probabilities of relapse-free and overall survival from 1, 3 and 5 years after transplantation were 100, 90 and 70 %, and 100, 90 and 80 %, respectively. Nevertheless, our analysis of long-term outcome after MAC allo-SCT for CLL suggests that younger patients with poorly controlled CLL may benefit from MAC allo-SCT.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Dreger P. Allotransplantation for chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program. 2009;602–9.

  2. Gribben JG. Stem cell transplantation in chronic lymphocytic leukemia. Biol Blood Marrow Transplant. 2009;15:53–8.

    Article  PubMed  Google Scholar 

  3. Weide R, Feiten S, Friesenhahn V, et al. Retreatment with bendamustine-containing regimens in patients with relapsed/refractory chronic lymphocytic leukemia and indolent B-cells lymphomas achieves high response rates and some long lasting remissions. Leuk Lymphoma. 2013;54:1640–6.

    Article  CAS  PubMed  Google Scholar 

  4. Gribben JG, Zahrieh D, Stephans K, et al. Autologous and allogeneic stem cell transplantation for poor-risk chronic lymphocytic leukemia. Blood. 2005;106:4389–96.

    Google Scholar 

  5. Pavletic ZS, Bierman PJ, Vose JM, et al. High incidence of relapse after autologous stem-cell transplantation for B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma. Ann Oncol. 1998;9:1023–6.

    Article  CAS  PubMed  Google Scholar 

  6. Ritgen M, Lange A, Stilgenbauer S, et al. Unmutated immunoglobulin variable heavy-chain gene status remains an adverse prognostic factor after autologous stem cell transplantation for chronic lymphocytic leukemia. Blood. 2003;101:2049–53.

    Article  CAS  PubMed  Google Scholar 

  7. Peres E, Braun T, Krijanovski O, et al. Reduced intensity versus full myeloablative stem cell transplant for advanced CLL. Bone Marrow Transplant. 2009;44:579–83.

    Article  CAS  PubMed  Google Scholar 

  8. Slavin S, Nagler A, Naparstek E, 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;91:756–63.

    CAS  PubMed  Google Scholar 

  9. Machaczka M, Johansson JE, Remberger M, et al. Allogeneic hematopoietic stem cell transplant with reduced-intensity conditioning for chronic lymphocytic leukemia in Sweden: does donor T-cell engraftment 3 months after transplant predict survival? Leuk Lymphoma. 2012;53:1699–705.

    Article  PubMed  Google Scholar 

  10. Döhner H, Stilgenbauer S, Benner A, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Eng J Med. 2000;343:1910–6.

    Article  Google Scholar 

  11. Ringdén O, Bäckman L, Lönnqvist B, et al. A randomized trial comparing use of cyclosporin and methotrexate for graft-versus-host disease prophylaxis in bone marrow transplant recipients with haematological malignancies. Bone Marrow Transplant. 1986;1:41–51.

    PubMed  Google Scholar 

  12. Ringdén O, Remberger M, Persson U, et al. Similar incidence of graft-versus-host disease using HLA-A, -B and -DR identical unrelated bone marrow donors as with HLA-identical siblings. Bone Marrow Transplant. 1995;15:619–25.

    PubMed  Google Scholar 

  13. Glucksberg H, Storb R, Fefer A, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation. 1974;18:295–304.

    Article  CAS  PubMed  Google Scholar 

  14. Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995;15:825–8.

    CAS  PubMed  Google Scholar 

  15. Kaplan E, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–81.

    Article  Google Scholar 

  16. Gooley TA, Leisenring W, Crowley J, Storer BE. Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med. 1999;18:695–706.

    Article  CAS  PubMed  Google Scholar 

  17. Milligan DW, Fernandes S, Dasgupta R, et al. Results of the MRC pilot study show autografting for younger patients with chronic lymphocytic leukemia is safe and achieves a high percentage of molecular responses. Blood. 2005;105:397–404.

    Article  CAS  PubMed  Google Scholar 

  18. Jantunen E, Itälä M, Siitonen T, et al. Autologous stem cell transplantation in patients with chronic lymphocytic leukaemia: the Finnish experience. Bone Marrow Transplant. 2006;37:1093–8.

    Article  CAS  PubMed  Google Scholar 

  19. Michallet M, Corront B, Hollard D, et al. Allogeneic bone marrow transplantation in chronic lymphocytic leukemia: 17 cases. Report from the EBMTG. Bone Marrow Transplant. 1991;7:275–9.

    CAS  PubMed  Google Scholar 

  20. Khouri IF, Keating MJ, Vriesendorp HM, et al. Autologous and allogeneic bone marrow transplantation for chronic lymphocytic leukemia: preliminary results. J Clin Oncol. 1994;12:748–58.

    CAS  PubMed  Google Scholar 

  21. Rabinowe SN, Soiffer RJ, Gribben JG, et al. Autologous and allogeneic bone marrow transplantation for poor prognosis patients with B-cell chronic lymphocytic leukemia. Blood. 1993;82:1366–76.

    CAS  PubMed  Google Scholar 

  22. Pavletic ZS, Arrowsmith ER, Bierman PJ, et al. Outcome of allogeneic stem cell transplantation for B cell chronic lymphocytic leukemia. Bone Marrow Transplant. 2000;25:717–22.

    Article  CAS  PubMed  Google Scholar 

  23. Pavletic SZ, Khouri IF, Haagenson M, et al. Unrelated donor marrow transplantation for B-cell chronic lymphocytic leukemia after using myeloablative conditioning: results from the Center for International Blood and Marrow Transplant research. J Clin Oncol. 2005;23:5788–94.

    Article  PubMed  Google Scholar 

  24. Michallet M, Archimbaud E, Bandini G, et al. HLA-identical sibling bone marrow transplantation in younger patients with chronic lymphocytic leukemia. European Group for Blood and Marrow Transplantation and the International Bone Marrow Transplant Registry. Ann Intern Med. 1996;124:311–5.

    Article  CAS  PubMed  Google Scholar 

  25. Doney KC, Chauncey T. Appelbaum FR; Seattle Bone Marrow Transplant Team. Allogeneic related donor hematopoietic stem cell transplantation for treatment of chronic lymphocytic leukemia. Bone Marrow Transplant. 2002;29:817–23.

    Article  CAS  PubMed  Google Scholar 

  26. Schetelig J, Thiede C, Bornhauser M, et al. Evidence of a graft-versus-leukemia effect in chronic lymphocytic leukemia after reduced-intensity conditioning and allogeneic stem-cell transplantation: the Cooperative German Transplant Study Group. J Clin Oncol. 2003;21:2747–53.

    Article  CAS  PubMed  Google Scholar 

  27. Khouri IF, Saliba RM, Admirand J, et al. Graft-versus-leukaemia effect after non-myeloablative haematopoietic transplantation can overcome the unfavourable expression of ZAP-70 in refractory chronic lymphocytic leukaemia. Br J Haematol. 2007;137:355–63.

    Article  CAS  PubMed  Google Scholar 

  28. Dreger P, Corradini P, Kimby E, et al. Indications for allogeneic stem cell transplantation in chronic lymphocytic leukemia: the EBMT transplant consensus. Leukemia. 2007;21:12–7.

    Article  CAS  PubMed  Google Scholar 

  29. Delgado J, Milligan DW, Dreger P. Allogeneic hematopoietic cell transplantation for chronic lymphocytic leukemia: ready for prime time? Blood. 2009;114:2581–8.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We acknowledge Nick Bolton, PhD for linguistic expertise.

Conflict of interest

The authors report no conflict of interest in this study.

Author information

Authors and Affiliations

  1. Division of Hematology, Department of Medicine at Huddinge, Karolinska Institutet, Stockholm, Sweden

    Maciej Machaczka, Björn Engelbrekt Wahlin, Hamdy Omar, Eva Kimby & Hans Hägglund

  2. Hematology Center Karolinska, Karolinska University Hospital Huddinge, M54, 141 86, Stockholm, Sweden

    Maciej Machaczka, Björn Engelbrekt Wahlin, Hamdy Omar, Eva Kimby & Hans Hägglund

  3. Department of Hematology and Coagulation, Sahlgrenska University Hospital, Göteborg, Sweden

    Jan-Erik Johansson

  4. Division of Clinical Immunology and Transfusion Medicine, Karolinska Institute, Stockholm, Sweden

    Mats Remberger

  5. Department of Hematology, Uppsala University Hospital, Uppsala, Sweden

    Helene Hallböök

  6. Department of Hematology, Skåne University Hospital and Lund University, Lund, Sweden

    Vladimir Lj Lazarevic & Gunnar Juliusson

  7. Department of Radiation Sciences, Section of Hematology, University of Umeå, Umeå, Sweden

    Anders Wahlin

Authors
  1. Maciej Machaczka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jan-Erik Johansson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mats Remberger
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Helene Hallböök
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Vladimir Lj Lazarevic
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Björn Engelbrekt Wahlin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hamdy Omar
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Anders Wahlin
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Gunnar Juliusson
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Eva Kimby
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Hans Hägglund
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maciej Machaczka.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Machaczka, M., Johansson, JE., Remberger, M. et al. High incidence of chronic graft-versus-host disease after myeloablative allogeneic stem cell transplantation for chronic lymphocytic leukemia in Sweden: graft-versus-leukemia effect protects against relapse. Med Oncol 30, 762 (2013). https://doi.org/10.1007/s12032-013-0762-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-013-0762-x

Keywords

Search

Navigation