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-Host Disease

Administration of short-term immunosuppressive agents after DLI reduces the incidence of DLI-associated acute GVHD without influencing the GVL effect

Bone Marrow Transplantation volume 44, pages 309–316 (2009)Cite this article

Abstract

Donor lymphocyte infusion (DLI) exerts a GVL effect, but its use is limited by a high incidence of GVHD. We retrospectively evaluated the efficacy of administering short-term immunosuppressive agents for prophylaxis against DLI-associated acute GVHD, and its influence on the GVL effect. Seventy patients with leukaemia received G-CSF primed DLI after HLA-identical sibling haematopoietic stem cell transplantation (HSCT) for treatment or prophylaxis against leukaemia relapse. Short-term immunosuppressive agents were given to 54 patients for prophylaxis against DLI-associated acute GVHD. Seventeen patients experienced acute GVHD; 30 patients developed chronic GVHD; and no GVHD-related death was observed. A significant difference was observed between the group that did not receive prophylaxis against GVHD or received prophylaxis for less than 2 weeks and the group that received prophylaxis for over 2 weeks (CsA or MTX at 10 mg/week) with regard to the incidence of DLI-associated acute GVHD (14/28 vs 3/42, P=0.000); no difference was observed in the relapse rate for prophylactic DLI patients between the two groups (4/10 vs 12/29). Using immunosuppressive agents for 2–4 weeks may reduce DLI-associated acute GVHD without influencing relapse and survival after G-CSF-primed DLI.

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

Similar content being viewed by others

References

  1. Grigg AP, Szer J, Beresford J, Dodds A, Bradstock K, Durrant S et al. Factors affecting the outcome of allogeneic bone marrow transplantation for adult patients with refractory or relapsed acute leukemia. Br J Haematol 1999; 107: 409–418.

    Article  CAS  PubMed  Google Scholar 

  2. Barrett AJ, Locatelli F, Treleaven JG, Gratwohl A, Szydło R, Zwaan FE . Second transplants for leukemic relapse after bone marrow transplantation: high early mortility but favorable effect of chronic GVHD on continued remission. Br J Haematol 1991; 79: 567–574.

    Article  CAS  PubMed  Google Scholar 

  3. Kolb HJ, Schattenberg A, Goldman JM, Hertenstein B, Jacobsen N, Arcese W et al. Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. European Group for Blood and Marrow Transplantation Working party Chronic Leukemia. Blood 1995; 86: 2041–2050.

    CAS  PubMed  Google Scholar 

  4. Collins Jr RH, Goldstein S, Giralt S, Levine J, Porter D, Drobyski W et al. Donor leukocyte infusions in acute lymphocytic leukemia. Bone Marrow Transplant 2000; 26: 511–516.

    Article  PubMed  Google Scholar 

  5. Alessandrino EP, Bernasconi P, Caldera D, Colombo A, Malcovati L, Martinelli G et al. Chemotherapy and donor peripheral blood progenitor cells for acute leukemia in early relapse after allogeneic bone marrow transplantation. Bone Marrow Transplant 1999; 23: 607–612.

    Article  CAS  PubMed  Google Scholar 

  6. Sohn SK, Jung JT, Kim DH, Lee NY, Seo KW, Chae YS et al. Prophylactic growth factor-primed donor lymphocyte infusion using cells reserved at the time of transplantation after allogeneic peripheral blood stem cell transplantation in patients with high-risk hematologic malignancies. Cancer 2002; 94: 18–24.

    Article  CAS  PubMed  Google Scholar 

  7. Huang X, Guo N, Ren H, Zhang Y, Gao Z, Lu D . An improved anti-leukemic effect achieved with donor progenitor cell infusion for relapse patients after allogeneic bone marrow transplantation. Chin Med J 2003; 116: 736–741.

    PubMed  Google Scholar 

  8. Huang XJ, Liu DH, Xu LP, Chen H, Han W, Liu KY et al. Prophylactic infusion of donor granulocyte colony stimulating factor mobilized peripheral blood progenitor cells after allogeneic hematological stem cell transplantation in patients with high-risk leukemia. Leukemia 2006; 20: 365–368.

    Article  CAS  PubMed  Google Scholar 

  9. Huang XJ, Liu DH, Liu KY, Xu LP, Chen H, Han W . Donor lymphocyte infusion for the treatment of leukemia relapse after HLA-mismatched/haploidentical T-cell-replete hematopoietic stem cell transplantation. Haematologica 2007; 92: 414–417.

    Article  PubMed  Google Scholar 

  10. Huang XJ, Wang Y, Liu DH, Xu LP, Chen H, Chen YH et al. Modified donor lymphocyte infusion (DLI) for the prophylaxis of leukemia relapse after hematopoietic stem cell transplantation in patients with advanced leukemia—feasibility and safety study. J Clin Immunol 2008; 28: 390–397.

    Article  CAS  PubMed  Google Scholar 

  11. Devergie A . Graft vs host disease. In: Apperley J, Carreras E, Gluckman E, Gratwohl A, Masszi T (eds). Haematopoietic Stem Cell Transplantation: The EBMT Handbook, Rev edn. European School of Hematology: Paris, France, 2004, pp 168–169.

    Google Scholar 

  12. Weisdorf D . GVHD—The Nuts and Bolts. In: Gewirtz AM, Winter JN, Zuckerman K (eds). American Society of Hematology Education Program Book. Washington, DC, USA, 2007, pp 62–67.

    Google Scholar 

  13. Schmid C, Schleuning M, Schwerdtfeger R, Hertenstein B, Mischak-Weissinger E, Bunjes D et al. Long-term survival in refractory acute myeloid leukemia after sequential treatment with chemotherapy and reduced-intensity conditioning for allogeneic stem cell transplantation. Blood 2006; 108: 1092–1099.

    Article  CAS  PubMed  Google Scholar 

  14. Slavin S, Naparastek E, Nagler A, Ackerstein A, Kapelushnik J, Or R . Allogeneic cell therapy for relapsed leukemia after bone marrow transplantation with donor peripheral blood lymphocytes. Exp Hematol 1995; 23: 1553–1562.

    CAS  PubMed  Google Scholar 

  15. Huang XJ, Chang YJ, Zhao XY . Maintaining hyporesponsiveness and polarization potential of T cells after in vitro mixture of G-CSF mobilized peripheral blood grafts and G-CSF primed bone marrow grafts in different proportions. Transplant immunol 2007; 17: 193–197.

    Article  CAS  Google Scholar 

  16. Huang XJ, Chang YJ, Zhao XY . In vivo induction of T-cell hyporesponsiveness and alteration of immunological cells of bone marrow grafts using granulocyte colony-stimulating factor. Haematologica 2004; 89: 1517–1524.

    Google Scholar 

  17. Chen SH, Li X, Huang XJ . Effect of recombinant granulocyte colony-stimulating factor on T-lymphocyte function and the mechanism of this effect. Int J Hematol 2004; 79: 178–184.

    Article  CAS  PubMed  Google Scholar 

  18. Zeng D, Dejbakhsh-Jones S, Strorber S . Granulocyte colony stimulating factor reduces the capacity of blood mononuclear cells to induce graft-versus-host disease: impact on blood progenitor cell transplantation. Blood 1997; 90: 453–463.

    CAS  PubMed  Google Scholar 

  19. Dazzi F, Szydlo RM, Cross NC, Craddock C, Kaeda J, Kanfer E et al. Durability of responses following donor lymphocyte infusions for patients who relapse after allogeneic stem cell transplantation for chronic myeloid leukemia. Blood 2000; 96: 2712–2716.

    CAS  PubMed  Google Scholar 

  20. Weisser M, Tischer J, Schnittger S, Schoch C, Ledderose G, Kolb HJ . A comparison of donor lymphocyte infusions or imatinib mesylate for patients with chronic myelogenous leukemia who have relapsed after allogeneic stem cell transplantation. Haematologica 2006; 91: 663–666.

    CAS  PubMed  Google Scholar 

  21. Collins RH, Shpilberg O, Drobyski WR, Porter DL, Giralt S, Champlin R et al. Donor leukocyte infusion in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation. J Clin Oncol 1997; 15: 433–444.

    Article  PubMed  Google Scholar 

  22. Kim JG, Sohn SK, Kim DH, Lee NY, Suh JS, Lee KS et al. A pilot study of cytoreductive chemotherapy combined with infusion of additional peripheral blood stem cells reserved at time of harvest for transplantation in case of relapsed hematologic malignancies after allogeneic peripheral blood stem cell transplant. Bone marrow transplant 2004; 33: 231–236.

    Article  CAS  PubMed  Google Scholar 

  23. Schmid C, Labopin M, Nagler A, Bornhäuser M, Finke J, Fassas A et al. Donor lymphocyte infusion in the treatment of first hematological relapse after allogeneic stem-cell transplantation in adults with acute myeloid leukemia: a retrospective risk factors analysis and comparison with other strategies by the EBMT acute leukemia working party. J Clin Oncol 2007; 25: 4938–4945.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Enpapers Team for critically reviewing this paper in English. This work was supported by the National Outstanding Young Scientist's Foundation of China (Grant no. 30725038), Hi-tech Research and Development Program of China (Grant no. 2006AA02Z4A0), Program for Innovative Research Team in University (Grant no. IRT 0702), Scientific Research Fund for Capital Medicine Development (Grant no. 2006-1010) and Leading Program of Clinical Faculty accredited by the Ministry of Health of China.

Author information

Authors and Affiliations

  1. Peking University People's Hospital, Peking University Institute of Hematology, Beijing, People's Republic of China

    X-J Huang, Y Wang, D-H Liu, L-P Xu, K-Y Liu, H Chen, Y-H Chen, W Han & H-X Shi

Authors
  1. X-J Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D-H Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L-P Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K-Y Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. H Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Y-H Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. W Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. H-X Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to X-J Huang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huang, XJ., Wang, Y., Liu, DH. et al. Administration of short-term immunosuppressive agents after DLI reduces the incidence of DLI-associated acute GVHD without influencing the GVL effect. Bone Marrow Transplant 44, 309–316 (2009). https://doi.org/10.1038/bmt.2009.26

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2009.26

Keywords

This article is cited by

Search

Advanced search

Quick links