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.

  • Letter to the Editor
  • Published:

A prospective multicenter study of unrelated bone marrow transplants using a reduced-intensity conditioning regimen with low-dose ATG-F

Bone Marrow Transplantation volume 51, pages 451–453 (2016)Cite this article

Subjects

Since Slavin et al.1 introduced a reduced-intensity conditioning (RIC) regimen using fludarabine (Flu), busulfan (Bu) and anti-T-lymphocyte globulin (ATG), similar regimens have been used worldwide.2, 3 Finke et al.4 reported that following a myeloablative conditioning regimen, ATG-Fresenius (ATG-F) administered as prophylaxis for GvHD reduced the incidences of acute and chronic GvHD without compromising survival in patients with unrelated hematopoietic stem cell transplantations.5 The major unresolved issue is the optimal dose of ATG in different conditioning regimens and populations. First, in terms of the conditioning regimen, Soiffer et al.6 reported that the addition of ATG to a RIC regimen was associated with inferior overall survival (OS) due to increased rates of relapse and non-relapse mortality (NRM),4 in contrast to the beneficial impact found with a myeloablative regimen.4 A large European Society for Blood and Marrow Transplantation (EBMT) study did not observe a negative impact of ATG<6 mg/kg on the outcome following a RIC regimen.7 Thus, the adverse effects might be the consequence of profound immunosuppression due to an excessive dose of ATG. These results suggest the possibility that the reduced dose of ATG might be appropriate in the setting of RIC. Second, in terms of ethnicity, it is well known that the risk of GvHD is lower in Asian than in Caucasian populations.8, 9, 10 Therefore, the dose of ATG might be reduced in Asian populations. Our group previously reported the clinical outcome in patients who underwent unrelated bone marrow transplantation (BMT) using low-dose ATG-F.11, 12 The incidence of acute and chronic GvHD were low considering patient characteristics such as HLA disparity and the low dose of ATG-F.

To confirm the feasibility of this RIC regimen containing low-dose ATG-F in combination with Flu plus Bu, we prospectively conducted a multicenter study in patients with hematological malignancies. This was a multicenter prospective study that assessed the feasibility of a RIC regimen containing Flu (30 mg/kg x 6 days), IV Bu (3.2 mg/kg x 2 days), and ATG-F (5 mg/kg per day at day −2). Twenty-seven patients were enrolled from January 2009 to March 2012. This study was approved by the Institutional Review Board of the National Cancer Center, Tokyo, Japan.

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

References

  1. Slavin S, Nagler A, Naparstek E, Kapelushnik Y, Aker M, Cividalli G 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 

  2. Bornhäuser M, Thiede C, Platzbecker U, Jenke A, Helwig A, Plettig R et al. Dose-reduced conditioning and allogeneic hematopoietic stem cell transplantation from unrelated donors in 42 patients. Clin Cancer Res 2001; 7: 2254–2262.

    PubMed  Google Scholar 

  3. Nagler A, Aker M, Or R, Naparstek E, Varadi G, Brautbar C 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 

  4. Finke JBW, Schmoor C, Ottinger HD, Stelljes M, Zander AR et al. ATG-Fresenius Trial Group.. Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors. Lancet Oncol 2009; 10: 855–864.

    Article  CAS  PubMed  Google Scholar 

  5. Socie G, Schmoor C, Bethge WA, Ottinger HD, Stelljes M, Zander AR et al. Chronic graft-versus-host disease: long-term results from a randomized trial on graft-versus-host disease prophylaxis with or without anti-T-cell globulin ATG-Fresenius. Blood 2011; 117: 6375–6382.

    Article  CAS  PubMed  Google Scholar 

  6. Soiffer RJ, Lerademacher J, Ho V, Kan F, Artz A, Champlin RE et al. Impact of immune modulation with anti-T-cell antibodies on the outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for hematologic malignancies. Blood 2011; 117: 6963–6970.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Baron F, Labopin M, Blaise D, Lopez-Corral L, Vigouroux S, Craddock C et al. Impact of in vivo T-cell depletion on outcome of AML patients in first CR given peripheral blood stem cells and reduced-intensity conditioning allo-SCT from a HLA-identical sibling donor: a report from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant 2014; 49: 389–396.

    Article  CAS  PubMed  Google Scholar 

  8. Oh H, Loberiza FR Jr, Zhang MJ, Ringden O, Akiyama H, Asai T et al. Comparison of graft-versus-host-disease and survival after HLA-identical sibling bone marrow transplantation in ethnic populations. Blood 2005; 105: 1408–1416.

    Article  CAS  PubMed  Google Scholar 

  9. Hahn T, McCarthy PL Jr, Zhang MJ, Wang D, Arora M, Frangoul H et al. Risk factors for acute graft-versus-host disease after human leukocyte antigen-identical sibling transplants for adults with leukemia. J Clin Oncol 2008; 26: 5728–5734.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Morishima Y, Kawase T, Malkki M, Morishima S, Spellman S, Kashiwase K et al. Significance of ethnicity in the risk of acute graft-versus-host disease and leukemia relapse after unrelated donor hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2013; 19: 1197–1203.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Fuji S, Ueno N, Hiramoto N, Asakura Y, Yakushijin K, Kamiyama Y et al. Reduced-intensity conditioning regimen with low-dose ATG-F for unrelated bone marrow transplant is associated with lower non-relapse mortality than a regimen with low-dose TBI: a single-center retrospective analysis of 103 cases. Int J Hematol 2013; 98: 608–614.

    Article  CAS  PubMed  Google Scholar 

  12. Hatanaka K, Fuji S, Ikegame K, Kato R, Wake A, Hidaka M et al. Low incidences of acute and chronic graft-versus-host disease after unrelated bone marrow transplantation with low-dose anti-T lymphocyte globulin. Int J Hematol 2012; 96: 773–780.

    Article  CAS  PubMed  Google Scholar 

  13. Petersdorf EW, Hansen JA, Martin PJ, Woolfrey A, Malkki M, Gooley T et al. Major-histocompatibility-complex class I alleles and antigens in hematopoietic-cell transplantation. N Engl J Med 2001; 345: 1794–1800.

    Article  CAS  PubMed  Google Scholar 

  14. Kanda Y . Investigation of the freely available easy-to-use software 'EZR' for medical statistics. Bone Marrow Transplant 2013; 48: 452–458.

    Article  CAS  PubMed  Google Scholar 

  15. Crocchiolo R, Esterni B, Castagna L, Furst S, El-Cheikh J, Devillier R et al. Two days of antithymocyte globulin are associated with a reduced incidence of acute and chronic graft-versus-host disease in reduced-intensity conditioning transplantation for hematologic diseases. Cancer 2013; 119: 986–992.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank the medical, nursing, data-processing, laboratory and clinical staff at the participating centers for their important contributions to this study and their dedicated patient care. This work was supported by grants from the Japanese Ministry of Health, Labour and Welfare and the National Cancer Research and Development Fund (23-A-28).

Author information

Authors and Affiliations

  1. Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan

    S Fuji, S-W Kim, S Kurosawa, T Yamashita & T Fukuda

  2. Division of Clinical Oncology and Hematology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan

    S Yano

  3. Division of Hematology, National Medical Center for Global Health and Medicine, Tokyo, Japan

    S Hagiwara

  4. Department of Hematology, Graduate School of Medicine, Osaka City University, Osaka, Japan

    H Nakamae

  5. Department of Hematology, National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan

    M Hidaka

  6. Division of Hematology, Department of Internal Medicine, Shinshu University School of Medicine, Nagano, Japan

    T Ito

  7. Division of Hematology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan

    K Ohashi

  8. Department of Hematology/Oncology, Wakayama Medical University Hospital, Wakayama, Japan

    K Hatanaka

  9. Department of Hematology and Oncology, Kanazawa University Hospital, Kanazawa, Japan

    A Takami

  10. Division of Biostatistics, Tohoku University Graduate School of Medicine, Miyagi, Japan

    T Yamaguchi

Authors
  1. S Fuji
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S-W Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S Yano
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S Hagiwara
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H Nakamae
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M Hidaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. T Ito
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. K Ohashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. K Hatanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. A Takami
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. S Kurosawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. T Yamashita
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. T Yamaguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. T Fukuda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S Fuji.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fuji, S., Kim, SW., Yano, S. et al. A prospective multicenter study of unrelated bone marrow transplants using a reduced-intensity conditioning regimen with low-dose ATG-F. Bone Marrow Transplant 51, 451–453 (2016). https://doi.org/10.1038/bmt.2015.268

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2015.268

This article is cited by

Search

Advanced search

Quick links