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:

Reduced Intensity Conditioning Regimens

A fludarabine-based dose-reduced conditioning regimen followed by allogeneic stem cell transplantation from related or unrelated donors in patients with myelodysplastic syndrome

Bone Marrow Transplantation volume 28, pages 643–647 (2001)Cite this article

Abstract

We investigated the feasibility and efficacy of a fludarabine-based dose-reduced conditioning regimen followed by stem cell transplantation from related (n = 5) or unrelated HLA-matched donors (n = 7) in 12 patients with high risk MDS, who were not eligible for a standard myeloablative conditioning regimen. The conditioning regimen consisted of fludarabine 30 mg/m2 daily for 6 days, busulfan 4 mg/kg daily for 2 days and anti-thymocyte globulin (ATG, rabbit) 10 mg/kg daily for 4 days in 11 patients, while one patient received fludarabine, ATG, cyclophosphamide and thiotepa. Graft-versus-host disease prophylaxis consisted of cyclosporine and a short course of methotrexate. The median age of the patients was 53 years (range 37–59). The median percentage of blasts in bone marrow aspirate at transplantation was 15% (range <5% to 35%). Diagnosis at transplant was RA (n = 1), RAEB (n = 5), RAEB-T (n = 5) and sAML (n = 1). A complex karyotype including monosomy 7 was noted in five patients. The reasons for using a dose-reduced conditioning regimen were prior autologous/syngeneic BMT (n = 4), active fungal infection (n = 2) or age/reduced performance status (n = 6). Engraftment was observed in all patients with complete donor chimerism. The incidence of acute GVHD (grade II–IV) was 33%. Eight patients died during follow-up due to relapse (n = 4), liver toxicity (n = 2), aspergillus (n = 1) or aGVHD grade IV (n = 1). After a median follow-up of 19 months, the 2-year estimated disease-free survival is 12% (95% CI: 2–23%) and the overall survival is 26% (95% CI: 4–52%). Fludarabine dose-reduced conditioning prior to allogeneic stem cell transplantation in high risk MDS patients, who were not eligible for standard transplantation, resulted in stable engraftment with complete chimerism, but the toxicity and relapse rate were considerable. Bone Marrow Transplantation (2001) 28, 643–647.

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

Similar content being viewed by others

References

  1. Bennett JM, Catovsky D, Daniel MD et al. Proposals for the classification of myelodysplastic syndromes Br J Haematol 1982 51: 189–199

    Article  CAS  Google Scholar 

  2. Geddes A, Bowen D, Jacobs A . Clonal karyotypic abnormalities and clinical progress in the myelodysplastic syndromes Br J Haematol 1990 76: 194–202

    Article  CAS  Google Scholar 

  3. De Witte T, Hermans J, Vossen J et al. Haematopoietic stem cell transplantation for patients with myelodysplastic syndromes and secondary acute myeloid leukemias: a report on behalf the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT) Br J Haematol 2000 110: 620–630

    Article  CAS  Google Scholar 

  4. Slavin S, Nagler A, Naperstek 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 diseases Blood 1998 91: 756–763

    CAS  Google Scholar 

  5. Giralt S, Estey E, Albitar M et al. Engraftment of allogeneic hematopoietic progenitor cells with purin analog-containing chemotherapy: harnessing graft-versus-leukemia effect without myeloablative therapy Blood 1997 89: 4531–4536

    CAS  Google Scholar 

  6. McSweeney P, Storb R . Establishing mixed chimerism with immunosuppressive, minimally myelosuppressive conditioning: preclinical and clinical studies American Society of Hematology Educational Book 1999 pp 396–405

  7. Child R, Clave E, Contentin N . Engraftment kinetics after nonmyeloablative allogeneic peripheral blood stem cell transplantation: full donor T-cell chimerism precedes alloimmune responses Blood 1999 94: 3234–3241

    Google Scholar 

  8. Przepiorka KM, Weisdorf D, Martin P . 1994 Consensus Conference on acute GVHD-grading Bone Marrow Transplant 1995 15: 825–828

    CAS  Google Scholar 

  9. Bearman SI, Appelbaum FR, Buckner CD . Regimen-related toxicity in patients undergoing bone marrow transplantation J Clin Oncol 1988 6: 1562–1568

    Article  CAS  Google Scholar 

  10. Kaplan EL, Meier P . Nonparametric estimation from incomplete observations J Am Stat Ass 1958 53: 457–460

    Article  Google Scholar 

  11. Rezvani K, Lalancette, Szydlo R et al. Non-myeloablative stem cell transplant in AML, ALL, and MDS: disappointing outcome for patients with advanced phase disease Blood 2000 96: (Suppl.) 2061

    Google Scholar 

  12. Shing MMK, Vowels M . Role of second bone marrow transplants Bone Marrow Transplant 1993 12: 21–24

    CAS  Google Scholar 

  13. Barrett AJ, Locatelli F, Treleaven JG et al. Second transplants for leukaemic relapse after bone marrow transplantation: high early mortality but favourable effect of chronic GvHD on continued remission Br J Haematol 1991 79: 567–571

    Article  CAS  Google Scholar 

  14. Nagler A, Or R, Naparstek E et al. Second allogeneic stem cell transplantation using nonmyeloablative conditioning for patients who relapsed or developed secondary malignancies following autologous transplantation Exp Hematol 2000 28: 1096–1104

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank the staff of the BMT unit for providing excellent care of our patients and the medical technicians for their excellent work in the BMT laboratory.

Author information

Authors and Affiliations

  1. Bone Marrow Transplantation, University Hospital Hamburg, Germany

    N Kröger, T Zabelina, W Krüger, H Renges, N Stute, J Schrum, H Kabisch & AR Zander

  2. Department of Hematology, Bone Marrow Transplantation, Charite University Berlin, Germany

    J Schetelig & W Siegert

Authors
  1. N Kröger
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J Schetelig
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T Zabelina
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. W Krüger
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H Renges
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. N Stute
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J Schrum
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. H Kabisch
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. W Siegert
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. AR Zander
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kröger, N., Schetelig, J., Zabelina, T. et al. A fludarabine-based dose-reduced conditioning regimen followed by allogeneic stem cell transplantation from related or unrelated donors in patients with myelodysplastic syndrome. Bone Marrow Transplant 28, 643–647 (2001). https://doi.org/10.1038/sj.bmt.1703215

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1703215

Keywords

This article is cited by

Search

Advanced search

Quick links