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:

T Cell Depletion

Antibody and pre- plus post-transplant prednisone treatments support T cell-depleted stem cell engraftment without drug-induced morbidity

Abstract

Rigorous T cell depletion methods can now be used to reduce the risk of graft-versus-host disease (GVHD) associated with allogeneic, hematopoietic stem cell transplantation (HSCT). However, full T cell depletion is also associated with a significant risk of graft failure. Here we hypothesize that engraftment failures after T cell-depleted HSCT may be due, in part, to the absence of GVHD prophylaxis. To test this hypothesis, we used a haploidentical mouse model to systematically measure the effects of immunosuppressive drug treatments and anti-T cell antibodies on engraftment. Results showed that engraftment was supported in all animals when hosts were pre-treated with anti-T cell antibodies, but donor chimerism was significantly improved when hosts were also treated with prednisone. Interestingly, when hosts received only pre-HSCT prednisone treatments, engraftment was not improved; when hosts received only post-HSCT prednisone (initiated near the time of irradiation), the animals became extremely ill. Results therefore demonstrated the need for both pre- and post-HSCT prednisone treatments as a means to ensure engraftment without morbidity in all host animals.

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

Access options

Buy this article

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

Similar content being viewed by others

References

  1. Lang P, Schumm M, Taylor G et al. Clinical scale isolation of highly purified peripheral CD34+ progenitors for autologous and allogeneic transplantation in children Bone Marrow Transplant 1999 24: 583 589

    Article  CAS  Google Scholar 

  2. Peters C, Matthes-Martin S, Fritsch G et al. Transplantation of highly purified peripheral blood CD34+ cells from HLA-mismatched parental donors in 14 children: evaluation of early monitoring of engraftment Leukemia 1999 13: 2070 2078

    Article  CAS  Google Scholar 

  3. Bornhauser M, Thiede C, Brendel C et al. Stable engraftment after megadose blood stem cell transplantation across the HLA barrier: the case for natural killer cells as graft-facilitating cells Transplantation 1999 68: 87 88

    Article  CAS  Google Scholar 

  4. Bachar-Lustig E, Rachamim N, Li HW et al. Megadose of T cell-depleted bone marrow overcomes MHC barriers in sublethally irradiated mice Nat Med 1995 1: 1268 1273

    Article  CAS  Google Scholar 

  5. Handgretinger R, Klingebiel T, Lang P et al. Megadose transplantation of purified peripheral blood CD34+ progenitor cells from HLA-mismatched parental donors in children Bone Marrow Transplant 2001 27: 777 783

    Article  CAS  Google Scholar 

  6. Martin PJ, Hansen JA, Torok-Storb B et al. Graft failure in patients receiving T cell-depleted HLA-identical allogeneic marrow transplants Bone Marrow Transplant 1988 3: 445 456

    CAS  Google Scholar 

  7. Patterson J, Prentice HG, Brenner MK et al. Graft rejection following HLA matched T-lymphocyte depleted bone marrow transplantation Br J Haematol 1986 63: 221 230

    Article  CAS  Google Scholar 

  8. Ash RC, Horowitz MM, Gale RP et al. Bone marrow transplantation from related donors other than HLA-identical siblings: effect of T cell depletion Bone Marrow Transplant 1991 7: 443 452

    CAS  Google Scholar 

  9. Bunjes D, Wiesneth M, Hertenstein B et al. Graft failure after T cell-depleted bone marrow transplantation: clinical and immunological characteristics and response to immunosuppressive therapy Bone Marrow Transplant 1990 6: 309 314

    CAS  PubMed  Google Scholar 

  10. Sharabi Y, Sachs DH . Engraftment of allogeneic bone marrow following administration of anti-T cell monoclonal antibodies and low-dose irradiation Transplant Proc 1989 21: 233 235

    CAS  PubMed  Google Scholar 

  11. Handgretinger R, Schumm M, Lang P et al. Transplantation of megadoses of purified haploidentical stem cells Ann NY Acad Sci 1999 872: 351 361

    Article  CAS  Google Scholar 

  12. Aversa F, Tabilio A, Velardi A et al. Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype New Engl J Med 1998 339: 1186 1193

    Article  CAS  Google Scholar 

  13. Bachar-Lustig E, Rachamim N, Li H-W et al. Megadose of T cell-depleted bone marrow overcomes MHC barriers in sublethally irradiated mice Nat Med 1995 1: 1268 1273

    Article  CAS  Google Scholar 

  14. Reisner Y, Martelli MF . Tolerance induction by ‘megadose’ transplants of CD34+ stem cells: a new option for leukemia patients without an HLA-matched donor Curr Opin Immunol 2000 12: 536 541

    Article  CAS  Google Scholar 

  15. Chao NJ, Snyder DS, Jain M et al. Equivalence of 2 effective graft-versus-host disease prophylaxis regimens: results of a prospective double-blind randomized trial Biol Blood Marrow Transplant 2000 6: 254 261

    Article  CAS  Google Scholar 

  16. Ross M, Schmidt GM, Niland JC et al. Cyclosporine, methotrexate, and prednisone compared with cyclosporine and prednisone for prevention of acute graft-vs.-host disease: effect on chronic graft-vs.-host disease and long-term survival Biol Blood Marrow Transplant 1999 5: 285 291

    Article  CAS  Google Scholar 

  17. Schlegel PG, Eyrich M, Bader P et al. OKT3-based reconditioning regimen for early graft failure in HLA-non-identical stem cell transplants Br J Haematol 2000 111: 668 673

    Article  CAS  Google Scholar 

  18. Hurwitz JL, McAndrew EC, Doherty PC . Anti-Thy-1 plus complement-treated cultured bone marrow cells resemble fetal thymocytes in killer cell function and marker expression J Immunol 1986 137: 1757 1763

    CAS  PubMed  Google Scholar 

  19. Yu C, Storb R, Mathey B et al. DLA-identical bone marrow grafts after low-dose total body irradiation: effects of high-dose corticosteroids and cyclosporine on engraftment Blood 1995 86: 4376 4381

    CAS  Google Scholar 

  20. Wagner JE . Prevention of graft failure by cyclosporine in rats receiving lymphocyte-depleted MHC-mismatched bone marrow Transplantation 1992 53: 624 628

    Article  CAS  Google Scholar 

  21. Ancin I, Ferra C, Gallardo D et al. Do corticosteroids add any benefit to standard GVHD prophylaxis in allogeneic BMT? Bone Marrow Transplant 2001 28: 39 45

    Article  CAS  Google Scholar 

  22. Sykes M, Szot GL, Swenson KA, Pearson DA . Induction of high levels of allogeneic hematopoietic reconstitution and donor-specific tolerance without myelosuppressive conditioning Nat Med 1997 3: 783 787

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported, in part, by Public Health Service grants P30 CA21765 and RO1 CA57419 from the National Institutes of Health, by the Assisi Foundation, and by the American Lebanese Syrian Associated Charities (ALSAC). We thank Drs Karen Slobod and Ely Benaim for useful discussions. We thank R Cross and M Paktinat for assistance with the FACScan.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

D'Costa, S., Hurwitz, J. Antibody and pre- plus post-transplant prednisone treatments support T cell-depleted stem cell engraftment without drug-induced morbidity. Bone Marrow Transplant 29, 553–556 (2002). https://doi.org/10.1038/sj.bmt.1703428

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1703428

Keywords

Search

Quick links