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:

Non-Myeloablative Stem Cell Transplants

Reduced intensity preparative regimens for allogeneic hematopoietic stem cell transplantation: a single center experience

Bone Marrow Transplantation volume 30, pages 651–659 (2002)Cite this article

Abstract

According to recent reports, fast engraftment with minimal transplant-related toxicity and mortality (TRT, TRM) can be achieved by using reduced-intensity preparative regimens in allogeneic hematopoietic stem cell transplantation (HSCT). We report our experience with related (39%) and unrelated (61%) HSCT in 44 high risk patients (AML, ALL, CML, CLL) receiving either busulfan/fludarabine or busulfane/fludarabine/ATG or TBI/fludarabine as reduced-intensity preparative regimens. Organ toxicity was minimal with mild mucositis and no major bleeding. Acute GVHD was recorded in 64% of the patients. Twenty-three patients achieved complete remission after transplantation, and complete chimerism was obtained in all patients with stable engraftment (35 patients). Twenty-nine patients died: 15 due to relapse/progression, 14 due to TRM. Survival with median follow-up of 18.5 months was significantly better in patients with matched related transplants compared to patients with other transplants. However, there was no difference between related and unrelated transplants with regard to engraftment, TRM and GVHD. In conclusion, our results in high-risk patients transplanted in CR or with smoldering leukemia from a related donor are encouraging, although a longer follow-up and a larger group of patients is needed in order to evaluate the role of different reduced-intensity preparative regimens in unrelated and related HSCT.

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

Similar content being viewed by others

References

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

    CAS  PubMed  Google Scholar 

  2. 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 disease Blood 1998 91: 756 763

    CAS  PubMed  Google Scholar 

  3. Khouri I, Keating M, Körbling M et al. Transplant-lite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor cell transplantation as treatment for lymphoid malignancies J Clin Oncol 1998 16: 2817 2824

    Article  CAS  PubMed  Google Scholar 

  4. 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 response Blood 1999 94: 3234 3241

    CAS  PubMed  Google Scholar 

  5. Wäsch R, Reisser S, Hahn J et al. Rapid achievement of complete donor chimerism and low regimen related toxicity after reduced conditioning with fludarabine, carmustine, melphalan and allogeneic transplantation Bone Marrow Transplant 2000 26: 243 250

    Article  PubMed  Google Scholar 

  6. Carella AM, Champlin R, Slavin S et al. Mini-allografts: ongoing trials in humans Bone Marrow Transplant 2000 25: 345 350

    Article  CAS  PubMed  Google Scholar 

  7. Bacigalupo A . Hematopoietic stem cell transplants after reduced intensity conditioning regimen (RI-HSCT): report of a workshop of the European group for blood and marrow transplantation (EBMT) Bone Marrow Transplant 2000 25: 803 805

    Article  CAS  PubMed  Google Scholar 

  8. Bornhäuser M, Thiede C, Schuler U et al. Dose-reduced conditioning for allogeneic blood stem cell transplantation: durable engraftment without antithymocyte globulin Bone Marrow Transplant 2000 26: 119 125

    Article  PubMed  Google Scholar 

  9. Anderlini P, Giralt S, Andersson B et al. Allogeneic stem cell transplantation with fludarabine-based, less intensive conditioning regimens as adoptive immunotherapy in advanced Hodgkin's disease Bone Marrow Transplant 2000 26: 615 620

    Article  CAS  PubMed  Google Scholar 

  10. Roemer E, Kiehl M, Guenzelmann S et al. Nonmyeloablative conditioning regimens in the treatment of hematological malignancies Blood 2000 96 (Supp. 1): 782a Abstr. 3381

    Google Scholar 

  11. McSweeney PA, Wagner JL, Maloney DG et al. Outpatient PBSC allografts using immunosuppression with low dose TBI before, and cyclosporine (CSP) and mycophenolate mofetil (MMF) after transplant Blood 1998 92 (Suppl. 1): 519a Abstr. 2133

    Google Scholar 

  12. Schetelig J, Held TK, Bornhäuser M et al. Nonmyeloablative allogeneic stem cell transplants in chronic lymphocytic leukemia from related and unrelated donors Blood 2000 96 (Suppl. 1): 200a Abstr. 857

    Google Scholar 

  13. Blau IW, Basara N, Serr A et al. A second unrelated bone marrow transplant: successful quantitative monitoring of mixed chimerism using a highly discriminative PCR-STR system Clin Lab Haem 1999 21: 133 138

    Article  CAS  Google Scholar 

  14. Basara N, Schmetzer B, Blau IW et al. Lenograstim-mobilized peripheral blood progenitor cells in volunteer donors: an open label randomized split dose escalating study Bone Marrow Transplant 2000 25: 371 376

    Article  CAS  PubMed  Google Scholar 

  15. Scharf SJ, Smith AG, Hansen JA et al. Quantitative determination of bone marrow transplant engraftment using fluorescent polymerase chain reaction primers for human identity markers Blood 1995 85: 1954 1963

    CAS  PubMed  Google Scholar 

  16. Przepiorka D, Weisdorf D, Martin P et al. Meeting report. Consensus conference on acute GVHD grading Bone Marrow Transplant 1995 15: 825 828

    CAS  PubMed  Google Scholar 

  17. Sullivan KM . Graft-versus-host disease In: Thomas ED, Blume KG, Forman SJ (eds) Hematopoietic Cell Transplantation Blackwell Science: Oxford 1999 pp 515 536

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  19. Bensinger WI, Clift R, Martin P et al. Allogeneic peripheral blood stem cell transplantation in patients with advanced hematologic malignancies: a retrospective comparison with marrow transplantation Blood 1996 88: 2794 2800

    CAS  PubMed  Google Scholar 

  20. Thomas ED, Storb R, Clift RA et al. Bone marrow transplantation New Engl J Med 1975 292: 832 843 895 902

    Article  CAS  PubMed  Google Scholar 

  21. Martin PJ . Overview of marrow transplantation immunology In: Thomas ED, Blume KG, Forman SJ (eds) Hematopoietic Cell Transplantation Blackwell Science: Oxford 1999 pp 19 27

    Google Scholar 

  22. 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 

  23. Carella AM, Lerma E, Dejana A et al. Engraftment of HLA-matched sibling hematopoietic stem cells after immunosuppressive conditioning regimen in patients with hematologic neoplasias Haematologica 1998 83: 904 909

    CAS  PubMed  Google Scholar 

  24. Carella AM, Cavaliere M, Lerma E et al. Autografting followed by nonmyeloablative immunosuppressive chemotherapy and allogeneic peripheral-blood hematopoietic stem-cell transplantation as treatment of resistant Hodgkin's disease and non-Hodgkin's lymphoma J Clin Oncol 2000 18: 3918 3924

    Article  CAS  PubMed  Google Scholar 

  25. Carella AM, Giralt S, Slavin S . Low intensity regimens with allogeneic hematopoietic stem cell transplantation as treatment of hematologic neoplasia Haematologica 2000 85: 304 313

    CAS  PubMed  Google Scholar 

  26. Khoury H, Adkins D, Brown R et al. Low incidence of transplantation-related acute complications in patients with chronic myeloid leukemia undergoing allogeneic stem cell transplantation with a low-dose (550 cGy) total body irradiation conditioning regimen Biol Blood Marrow Transplant 2001 7: 352 358

    Article  CAS  PubMed  Google Scholar 

  27. Nagler A, Slavin S, Varadi G et al. Allogeneic peripheral blood stem cell transplantation using a fludarabine-based low intensity conditioning regimen for malignant lymphoma Bone Marrow Transplant 2000 25: 1021 1028

    Article  CAS  PubMed  Google Scholar 

  28. Martino R, Caballero MD, Canals C et al. Reduced-intensity conditioning reduces the risk of severe infections after allogeneic peripheral blood stem cell transplantation Bone Marrow Transplant 2001 28: 341 347

    Article  CAS  PubMed  Google Scholar 

  29. Giralt S, Thall PF, Khouri I et al. Melphalan and purineanalog-containing preparative regimens: reduced-intensity conditioning for patients with hematological malignancies undergoing allogeneic stem cell transplantation Blood 2001 97: 631 637

    Article  CAS  PubMed  Google Scholar 

  30. Kottaridis PD, Milligan DW, Chopra R et al. In vivo CAMPATH-1H prevents graft-versus-host disease following nonmyeloablative stem cell transplantation Blood 2000 96: 2419 2425

    CAS  PubMed  Google Scholar 

  31. Horowitz MM, Gale RP, Sondel PM et al. Graft-versus leukemia reactions after bone marrow transplantation Blood 1990 75: 555 562

    CAS  PubMed  Google Scholar 

  32. Schattenberg A, Schaap N, Preijers F et al. Outcome of T cell-depleted transplantation after conditioning with an intensified regimen in patients aged 50 years or more is comparable with that in younger patients Bone Marrow Transplant 2000 26: 17 22

    Article  CAS  PubMed  Google Scholar 

  33. Schmidt GM, Horak DA, Niland JC et al. A randomized controlled trial of prophylactic ganciclovir for cytomegalovirus pulmonary infection in allogeneic bone marrow transplant recipients New Engl J Med 1991 324: 1005 1011

    Article  CAS  PubMed  Google Scholar 

  34. Einsele B, Ehninger G, Hebart H et al. Polymerase chain reaction monitoring reduces the incidence of cytomegalovirus disease and the duration and side-effects of antiviral therapy after bone marrow transplantation Blood 1995 86: 2815 2820

    CAS  PubMed  Google Scholar 

  35. Boeckh M, Gooley TA, Myerson D et al. Cytomegalovirus pp65 antigenemia-guided early treatment with ganciclovir versus ganciclovir at engraftment after allogeneic bone marrow transplantation: a randomized double-blind study Blood 1996 10: 4063 4071

    Google Scholar 

  36. Mohty M, Faucher C, Vey N et al. High rate of secondary viral and bacterial infections in patients undergoing allogeneic bone marrow mini-transplantation Bone Marrow Transplant 2000 26: 252 255

    Article  Google Scholar 

Download references

Acknowledgements

We thank Ms Kilb, Dr Seidl and Professor Seifried, Institute for Transfusion Medicine and Immunohematology, Frankfurt/Main, for chimerism analysis.

Author information

Authors and Affiliations

  1. Clinic for Bone Marrow Transplantation and Hematology/Oncology, Idar-Oberstein, Germany

    N Basara, E Roemer, L Kraut, S Guenzelmann, B Schmetzer, MG Kiehl & AA Fauser

Authors
  1. N Basara
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E Roemer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L Kraut
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S Guenzelmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. B Schmetzer
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. MG Kiehl
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. AA Fauser
    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

Basara, N., Roemer, E., Kraut, L. et al. Reduced intensity preparative regimens for allogeneic hematopoietic stem cell transplantation: a single center experience. Bone Marrow Transplant 30, 651–659 (2002). https://doi.org/10.1038/sj.bmt.1703697

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1703697

Keywords

This article is cited by

Search

Advanced search

Quick links