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

Feasibility of reduced intensity hematopoietic stem cell transplantation from an HLA-matched unrelated donor

Summary:

To evaluate the feasibility of reduced intensity stem cell transplantation (RIST) with bone marrow from a matched unrelated donor (MUD), we retrospectively investigated 20 patients with hematological disorders who received RIST in the Tokyo SCT consortium from January 2000 to October 2002. The preparative regimens were fludarabine-based (150–180 mg/m2, n=18) or cladribine-based (0.77 mg/kg, n=2). To enhance engraftment, antithymocyte globulin (ATG) and 4 or 8 Gy total body irradiation (TBI) were added to these regimens in nine and 11 patients, respectively. GVHD prophylaxis was cyclosporine with or without methotrexate. In all, 19 achieved primary engraftment. Three developed graft failure (one primary, two secondary), and five died of treatment-related mortality within 100 days of transplant. Seven of the 19 patients who achieved initial engraftment developed grade II–IV acute GVHD, and seven of 13 patients who survived >100 days developed chronic GVHD. At a median follow-up of 5.5 months, estimated 1-year overall survival was 35%. Compared with a TBI-containing regimen, an ATG-containing regimen was associated with a high risk of graft failure (30 vs 0%, P=0.0737). This study supports the feasibility of RIST from MUD; however, procedure-related toxicities remain significant in its application to patients.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Khouri IF, Keating M, Korbling 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 

  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 diseases. Blood 1998; 91: 756–763.

    CAS  PubMed  Google Scholar 

  3. Grewal SS, Barker JN, Davies SM, Wagner JE . Unrelated donor hematopoietic cell transplantation: marrow or umbilical cord blood? Blood 2003; 101: 4233–4244.

    Article  CAS  PubMed  Google Scholar 

  4. Kodera Y, Morishima Y, Kato S et al. Analysis of 500 bone marrow transplants from unrelated donors (UR-BMT) facilitated by the Japan Marrow Donor Program: confirmation of UR-BMT as a standard therapy for patients with leukemia and aplastic anemia. Bone Marrow Transplant 1999; 24: 995–1003.

    Article  CAS  PubMed  Google Scholar 

  5. Sasazuki T, Juji T, Morishima Y et al. Effect of matching of class I HLA alleles on clinical outcome after transplantation of hematopoietic stem cells from an unrelated donor. Japan Marrow Donor Program. N Engl J Med 1998; 339: 1177–1185.

    Article  CAS  PubMed  Google Scholar 

  6. Saito T, Kanda Y, Kami M et al. Therapeutic potential of a reduced intensity preparative regimen for allogeneic transplantation with cladribine, busulfan, and antithymocyte globulin against advanced/refractory acute leukemia/lymphoma. Clin Cancer Res 2002; 8: 1014–1020.

    CAS  PubMed  Google Scholar 

  7. Thiede C, Florek M, Bornhauser M et al. Rapid quantification of mixed chimerism using multiplex amplification of short tandem repeat markers and fluorescence detection. Bone Marrow Transplant 1999; 23: 1055–1060.

    Article  CAS  PubMed  Google Scholar 

  8. Kanda Y, Mineishi S, Saito T et al. Long-term low-dose acyclovir against varicella-zoster virus reactivation after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 2001; 28: 689–692.

    Article  CAS  PubMed  Google Scholar 

  9. Pizzo PA . Management of fever in patients with cancer and treatment-induced neutropenia. N Engl J Med 1993; 328: 1323–1332.

    Article  CAS  PubMed  Google Scholar 

  10. Przepiorka D, Weisdorf D, Martin P et al. 1994 consensus conference on acute GVHD grading. Bone Marrow Transplant 1995; 15: 825–828.

    CAS  PubMed  Google Scholar 

  11. Sullivan KM, Agura E, Anasetti C et al. Chronic graft-versus-host disease and other late complications of bone marrow transplantation. Semin Hematol 1991; 28: 250–259.

    CAS  PubMed  Google Scholar 

  12. Wong R, Giralt SA, Martin T et al. Reduced intensity conditioning for unrelated donor hematopoietic stem cell transplantation as treatment of myeloid malignancies in patients older than 55 years of age. Blood 2003; 102: 3052–3059.

    Article  CAS  PubMed  Google Scholar 

  13. Nagler A, Aker M, Or R et al. Low-intensity conditioning is sufficient to ensure engraftment in matched unrelated bone marrow transplantation. Exp Hematol 2001; 29: 362–370.

    Article  CAS  PubMed  Google Scholar 

  14. Bornhauser M, Thiede C, Platzbecker U et al. Dose-reduced conditioning and allogeneic hematopoietic stem cell transplantation from unrelated donors in 42 patients. Clin Cancer Res 2001; 7: 2254–2262.

    CAS  PubMed  Google Scholar 

  15. Maris MB, Niederwieser D, Sandmaier BM et al. HLA-matched unrelated donor hematopoietic cell transplantation after nonmyeloablative conditioning for patients with hematologic malignancies. Blood 2003; 102: 2021–2030.

    Article  CAS  PubMed  Google Scholar 

  16. Eiermann TH, Lambrecht P, Zander AR . Monitoring anti-thymocyte globulin (ATG) in bone marrow recipients. Bone Marrow Transplant 1999; 23: 779–781.

    Article  CAS  PubMed  Google Scholar 

  17. Bunn D, Lea CK, Bevan DJ et al. The pharmacokinetics of anti-thymocyte globulin (ATG) following intravenous infusion in man. Clin Nephrol 1996; 45: 29–32.

    CAS  PubMed  Google Scholar 

  18. Deeg HJ, Amylon ID, Harris RE et al. Marrow transplants from unrelated donors for patients with aplastic anemia: minimum effective dose of total body irradiation. Biol Blood Marrow Transplant 2001; 7: 208–215.

    Article  CAS  PubMed  Google Scholar 

  19. Takenaka K, Gondo H, Tanimoto K et al. Increased incidence of cytomegalovirus (CMV) infection and CMV-associated disease after allogeneic bone marrow transplantation from unrelated donors. The Fukuoka Bone Marrow Transplantation Group. Bone Marrow Transplant 1997; 19: 241–248.

    Article  CAS  PubMed  Google Scholar 

  20. Kanda Y, Mineishi S, Nakai K et al. Frequent detection of rising cytomegalovirus antigenemia after allogeneic stem cell transplantation following a regimen containing antithymocyte globulin. Blood 2001; 97: 3676–3677.

    Article  CAS  PubMed  Google Scholar 

  21. Fukuda T, Boeckh M, Carter RA et al. Risks and outcomes of invasive fungal infections in recipients of allogeneic hematopoietic stem cell transplants after nonmyeloablative conditioning. Blood 2003; 102: 827–833.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Consortia

Corresponding author

Correspondence to M Kami.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kusumi, E., Kami, M., Yuji, K. et al. Feasibility of reduced intensity hematopoietic stem cell transplantation from an HLA-matched unrelated donor. Bone Marrow Transplant 33, 697–702 (2004). https://doi.org/10.1038/sj.bmt.1704425

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1704425

Keywords

This article is cited by

Search

Quick links