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:

Graft Versus Tumor Effects

Reduced-intensity conditioning using TBI (8 Gy), fludarabine, cyclophosphamide and ATG in elderly CML patients provides excellent results especially when performed in the early course of the disease

Bone Marrow Transplantation volume 34, pages 1083–1088 (2004)Cite this article

Summary:

Allogeneic bone marrow or stem cell transplantation is a curative therapeutic option for chronic myelogenous leukemia. In order to decrease the toxicity of the procedure, the dosage of total body irradiation was reduced from 12 to 8 Gy and subsequently the dose of cyclophosphamide from 120 to 80 mg/kg. The purine analogue fludarabine, ATG, cyclosporine A and a short course of methotrexate were given for immune suppression. So far, 35 elderly CML patients with sibling and unrelated donors have been transplanted. Transplant-related mortality at day +100 was 11%. After engraftment, all patients achieved a complete cytogenetic remission. Relapse occurred in 14% of the patients. The risk of relapse was significantly higher in those patients transplanted in second chronic or accelerated phase (P=0.048). After a median follow-up of 30 months (range 12–62), 63% of the patients are alive. Those patients transplanted within the first year from diagnosis had an overall survival of 79% (P=0.049), emphasizing the benefit of early transplantation. Stepwise reduction of conditioning intensity resulted in stable engraftment, low relapse rates and encouraging overall survival in this high-risk patient group.

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
Figure 6

Similar content being viewed by others

References

  1. Thomas ED . Stem cell transplantation: past, present and future. Stem Cells 1994; 12: 539–544.

    Article  PubMed  Google Scholar 

  2. Santos GW, Tutschka PJ, Brookmeyer R et al. Marrow transplantation for acute nonlymphocytic leukaemia after treatment with busulfan and cyclophosphamide. N Engl J Med 1983; 309: 1347–1353.

    Article  CAS  PubMed  Google Scholar 

  3. Gratwohl A, Hermans J, Goldman JM et al. Risk assessment for patients with chronic myeloid leukaemia before allogeneic blood or marrow transplantation. Lancet 1998; 352: 1087–1092.

    Article  CAS  PubMed  Google Scholar 

  4. Schleuning M, Gunther W, Ledderose G, Kolb HJ . Dose-dependent effects of in vivo antithymocyte globulin during conditioning for allogeneic bone marrow transplantation from unrelated donors in patients with chronic phase CML. Bone Marrow Transplant 2003; 32: 243–250.

    Article  CAS  PubMed  Google Scholar 

  5. Przepiorka D, Smith TL, Folloder J et al. Risk factors for acute graft-versus-host disease after allogeneic blood stem cell transplantation. Blood 1999; 94: 1465–1470.

    CAS  PubMed  Google Scholar 

  6. Lee SJ . Chronic myelogenous leukaemia. Br J Haematol 2000; 111: 993–1009.

    Article  CAS  PubMed  Google Scholar 

  7. Kolb HJ, Schattenberg A, Goldman JM et al. Graft-versus-leukaemia effect of donor lymphocyte transfusions in marrow grafted patients. European Group for Blood and Marrow Transplantation Working Party Chronic Leukaemia. Blood 1995; 86: 2041–2050.

    CAS  PubMed  Google Scholar 

  8. Kolb HJ, Mittermuller J, Clemm C et al. Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukaemia in marrow transplant patients. Blood 1990; 76: 2462–2465.

    CAS  PubMed  Google Scholar 

  9. McSweeney PA, Niederwieser D, Shizuru JA et al. Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood 2001; 97: 3390–3400.

    Article  CAS  PubMed  Google Scholar 

  10. Hill GR, Crawford JM, Cooke KR et al. Total body irradiation and acute graft-versus-host disease: the role of gastrointestinal damage and inflammatory cytokines. Blood 1997; 90: 3204–3213.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  12. Giralt S, Thall PF, Khouri I et al. Melphalan and purine analog-containing preparative regimens: reduced-intensity conditioning for patients with hematologic malignancies undergoing allogeneic progenitor cell transplantation. Blood 2001; 97: 631–637.

    CAS  PubMed  Google Scholar 

  13. McSweeney PA, Storb R . Mixed chimerism: preclinical studies and clinical applications. Biol Blood Marrow Transplant 1999; 5: 192–203.

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  15. Raiola AM, Van Lint MT, Lamparelli T et al. Reduced intensity thiotepa–cyclophosphamide conditioning for allogeneic haemopoietic stem cell transplants (HSCT) in patients up to 60 years of age. Br J Haematol 2000; 109: 716–721.

    Article  CAS  PubMed  Google Scholar 

  16. Maurer J, Janssen JW, Thiel E et al. Detection of chimeric BCR-ABL genes in acute lymphoblastic leukaemia by polymerase chain reaction. Lancet 1991; 337: 1055–1058.

    Article  CAS  PubMed  Google Scholar 

  17. Emig M, Saussele S, Wittor H et al. Accurate and rapid analysis of residual disease in patients with CML using specific fluorescent hybridization probes for real time quantitative RT-PCR. Leukaemia 1999; 13: 1825–1832.

    Article  CAS  Google Scholar 

  18. Sloand E, Childs RW, Solomon S et al. The graft-versus-leukemia effect of nonmyeloablative stem cell allografts may not be sufficient to cure chronic myelogenous leukemia. Bone Marrow Transplant 2003; 32: 897–901.

    Article  CAS  PubMed  Google Scholar 

  19. Clift RA, Buckner CD, Thomas ED et al. Marrow transplantation for chronic myeloid leukaemia: a randomized study comparing cyclophosphamide and total body irradiation with busulfan and cyclophosphamide. Blood 1994; 84: 2036–2043.

    CAS  PubMed  Google Scholar 

  20. McGlave PB, Shu XO, Wen W et al. Unrelated donor marrow transplantation for chronic myelogenous leukaemia: 9 years' experience of the National Marrow Donor Program. Blood 2000; 95: 2219–2225.

    CAS  PubMed  Google Scholar 

  21. Bornhäuser M, Kiehl M, Siegert W et al. Dose-reduced conditioning for allografting in 44 patients with chronic myeloid leukaemia: a retrospective analysis. Br J Haematol 2001; 115: 119–124.

    Article  PubMed  Google Scholar 

  22. Niederwieser D, Maris M, Shiruzu JA et al. Low-dose total body irradiation and fludarabine followed by haematopoietic 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 haematological diseases. Blood 2003; 101: 1620–1629.

    Article  CAS  PubMed  Google Scholar 

  23. Blum W, Brown R, Lin HS et al. Low-dose (550 cGy), single-exposure total body irradiation and cyclophosphamide: consistent, durable engraftment of related-donor peripheral blood stem cells with low treatment related mortality and fatal organ toxicity. Biol Blood Marrow Transplant 2002; 8: 608–618.

    Article  CAS  PubMed  Google Scholar 

  24. Bensinger WI, Martin PJ, Storer B . Transplantation of bone marrow as compared with peripheral blood stem cells from HLA identical relatives in patients with hematological cancers. N Engl J Med 2001; 344: 175–181.

    Article  CAS  PubMed  Google Scholar 

  25. Schmitz N, Beksac M, Hasenclever D et al. Transplantation of mobilized peripheral blood cells to HLA identical siblings with standard risk leukemia. Blood 2002; 100: 761–767.

    Article  CAS  PubMed  Google Scholar 

  26. Elmaagacli AH, Beelen DW, Opalka B et al. The risk of residual molecular and cytogenetic disease in patients with Philadelphia-chromosome positive first chronic phase chronic myelogenous leukemia is reduced after transplantation of allogeneic peripheral blood stem cells compared with bone marrow. Blood 1999; 94: 384–389.

    CAS  PubMed  Google Scholar 

  27. O'Brien SG, Guilhot F, Larson RA et al. The IRIS investigators. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukaemia. N Engl J Med 2003; 348: 994–1004.

    Article  CAS  PubMed  Google Scholar 

  28. Druker BJ, O'Brien SG, Cortes J, Radich J . Chronic myelogenous leukemia. Hematology (Am Soc Hematol Educ Program) 2002, 11–135.

Download references

Author information

Authors and Affiliations

  1. Department of Medicine III, Clinical Cooperative Group for Haematopoietic Cell Transplantation, University of Munich, Klinikum Grosshadern and GSF- National Research Center for Environment and Health, Munich, Germany

    M Weisser, G Ledderose, S Schnittger, C Schoch & H J Kolb

  2. Center for Bone Marrow Transplantation, Stiftung Deutsche Klinik fuer Diagnostik, Wiesbaden, Germany

    M Schleuning & R Schwerdtfeger

  3. Institut of Legal Medicine, Ludwig Maximilians University of Munich, Germany

    B Rolf

Authors
  1. M Weisser
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M Schleuning
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G Ledderose
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. B Rolf
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S Schnittger
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. C Schoch
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. R Schwerdtfeger
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. H J Kolb
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M Weisser.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Weisser, M., Schleuning, M., Ledderose, G. et al. Reduced-intensity conditioning using TBI (8 Gy), fludarabine, cyclophosphamide and ATG in elderly CML patients provides excellent results especially when performed in the early course of the disease. Bone Marrow Transplant 34, 1083–1088 (2004). https://doi.org/10.1038/sj.bmt.1704664

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1704664

Keywords

This article is cited by

Search

Advanced search

Quick links