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:

Chimerism

Low T-cell chimerism is not followed by graft rejection after nonmyeloablative stem cell transplantation (NMSCT) with CD34-selected PBSC

Bone Marrow Transplantation volume 32, pages 829–834 (2003)Cite this article

Summary:

We investigate the feasibility of CD34-selected peripheral blood stem cell (PBSC) transplantation followed by pre-emptive CD8-depleted donor lymphocyte infusions (DLI) after a minimal conditioning regimen. Six patients with advanced hematological malignancies ineligible for a conventional myeloablative transplant (n=5) or metastatic renal cell carcinoma (n=1), and with an HLA-identical (n=4) or alternative (n=2) donor were included. The nonmyeloablative conditioning regimen consisted in 2 Gy TBI alone (n=4), 2 Gy TBI and fludarabine (RCC patient, n=1) or cyclophosphamide and fludarabine (patient who had previously received 12 Gy TBI, n=1). Post transplant immunosuppression was carried out with cyclosporin (CyA) and mycophenolate mofetil (MMF). Initial engraftment was achieved in all patients. One out of six patients (17%) experienced grade ⩾2 acute GVHD only after abrupt cyclosporin discontinuation and α interferon therapy for life-threatening tumor progression. T-cell chimerism was 23% (19–30) on day 28, 32% (10–35) on day 100, 78% (49–95) on day 180 and 99.5% (99–100) on day 365. Three out of four patients who had measurable disease before the transplant experienced a complete response. We conclude that CD34-selected NMSCT followed by CD8-depleted DLI is feasible and preserves engraftment and apparently also the graft-versus-leukemia (GVL) effect. Further studies are needed to confirm this encouraging preliminary report.

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

Similar content being viewed by others

References

  1. Baron F, Beguin Y . Nonmyeloablative allogeneic hematopoietic stem cell transplantation. J Hematother Stem Cell Res 2002; 11: 243–263.

    Article  CAS  Google Scholar 

  2. Storb R . Allogeneic hematopoietic stem cell transplantation—yesterday, today, and tomorrow. Exp Hematol 2003; 31: 1–10.

    Article  Google Scholar 

  3. 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  Google Scholar 

  4. Storb R, Yu C, Wagner JL et al. Stable mixed hematopoietic chimerism in DLA-identical littermate dogs given sublethal total body irradiation before and pharmacological immunosuppression after marrow transplantation. Blood 1997; 89: 3048–3054.

    CAS  Google Scholar 

  5. McSweeney PA, Storb R . Mixed chimerism: preclinical studies and clinical applications. Biol Blood Marrow Transplant 1999; 5: 192–203.

    Article  CAS  Google Scholar 

  6. Zaucha JM, Zellmer E, Georges G et al. G-CSF-mobilized peripheral blood mononuclear cells added to marrow facilitates engraftment in nonmyeloablated canine recipients: CD3 cells are required. Biol Blood Marrow Transplant 2001; 7: 613–619.

    Article  CAS  Google Scholar 

  7. Zaucha JM, Yu C, Zellmer E et al. Effects of extending the duration of postgrafting immunosuppression and substituting granulocyte-colony-stimulating factor-mobilized peripheral blood mononuclear cells for marrow in allogeneic engraftment in a nonmyeloablative canine transplantation model. Biol Blood Marrow Transplant 2001; 7: 513–516.

    Article  CAS  Google Scholar 

  8. Zaucha JA, Yu C, Lothrop Jr CD et al. Severe canine hereditary hemolytic anemia treated by nonmyeloablative marrow transplantation. Biol Blood Marrow Transplant 2001; 7: 14–24.

    Article  CAS  Google Scholar 

  9. McSweeney PA, Niederwieser D, Shizuru J 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  Google Scholar 

  10. Niederwieser D, Maris M, Shizuru JA et al. Low-dose total body irradiation (TBI) and fludarabine followed by hematopoietic cell transplantation (HCT) from HLA-matched or mismatched unrelated donors and postgrafting immunosuppression with cyclosporine and mycophenolate mofetil (MMF) can induce durable complete chimerism and sustained remissions in patients with hematological diseases. Blood 2003; 101: 1620–1629.

    Article  CAS  Google Scholar 

  11. Pelot MR, Pearson DA, Swenson K et al. Lymphohematopoietic graft-versus-host reactions can be induced without graft-versus-host disease in murine mixed chimeras established with a cyclophosphamide-based non-myeloablative conditioning regimen. Biol Blood Marrow Transplant 1999; 5: 133–143.

    Article  CAS  Google Scholar 

  12. Mapara MY, Kim YM, Wang SP et al. Donor lymphocyte infusions mediate superior graft-versus-leukemia effects in mixed compared to fully allogeneic chimeras: a critical role for host antigen-presenting cells. Blood 2002; 100: 1903–1909.

    Article  CAS  Google Scholar 

  13. Baron F, Beguin Y . Preemptive cellular immunotherapy after T-cell-depleted allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2002; 8: 351–359.

    Article  CAS  Google Scholar 

  14. Baron F, Siquet J, Schaaf-Lafontaine N et al. Pre-emptive immunotherapy with CD8-depleted donor lymphocytes after CD34-selected allogeneic peripheral blood stem cell transplantation. Haematologica 2002; 87: 78–88.

    PubMed  Google Scholar 

  15. Baron F, Baudoux E, Frere P et al. Nonmyeloablative stem cell transplantation with CD8-depleted or CD34- selected peripheral blood stem cells. J Hematother Stem Cell Res 2002; 11: 301–314.

    Article  Google Scholar 

  16. Baron F, Baudoux E, Fillet G, Beguin Y . Retrospective comparison of CD34-selected allogeneic peripheral blood stem cell transplantation followed by CD8-depleted donor lymphocyte infusions with unmanipulated bone marrow transplantation. Hematology 2002; 7: 137–143.

    Article  Google Scholar 

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

    CAS  Google Scholar 

  18. Margolis J, Vogelsang G . Chronic graft-versus-host disease. J Hematother Stem Cell Res 2000; 9: 339–346.

    Article  CAS  Google Scholar 

  19. Thiede C, Bornhausser M, Oelschlägel U et al. Sequential monitoring of chimerism and detection of minimal residual disease after allogeneic bone marrow transplantation (BSCT) using multiplex PCR amplification of short tandem repeat markers. Leukemia 2001; 15: 293–302.

    Article  CAS  Google Scholar 

  20. Bearman SI, Appelbaum FR, Buckner CD et al. Regimen-related toxicity in patients undergoing bone marrow transplantation. J Clin Oncol 1988; 6: 1562–1568.

    Article  CAS  Google Scholar 

  21. Kreiter S, Winkelmann N, Schneider PM et al. Failure of sustained engraftment after non-myeloablative conditioning with low-dose TBI and T cell-reduced allogeneic peripheral stem cell transplantation. Bone Marrow Transplant 2001; 28: 157–161.

    Article  CAS  Google Scholar 

  22. Gorner M, Kordelas L, Thalheimer M et al. Stable mixed chimerism after T cell-depleted allogeneic hematopoietic stem cell transplantation using conditioning with low-dose total body irradiation and fludarabine. Bone Marrow Transplant 2002; 29: 621–624.

    Article  CAS  Google Scholar 

  23. Spitzer TR, McAfee S, Sackstein R et al. Intentional induction of mixed chimerism and achievement of antitumor responses after nonmyeloablative conditioning therapy and HLA-matched donor bone marrow transplantation for refractory hematologic malignancies. Biol Blood Marrow Transplant 2000; 6: 309–320.

    Article  CAS  Google Scholar 

  24. Dey BR, McAfee S, Sackstein R et al. Successful allogeneic stem cell transplantation with nonmyeloablative conditioning in patients with relapsed hematologic malignancy following autologous stem cell transplantation. Biol Blood Marrow Transplant 2001; 7: 604–612.

    Article  CAS  Google Scholar 

  25. Orsini E, Alyea EP, Chillemi A et al. Conversion to full donor chimerism following donor lymphocyte infusion is associated with disease response in patients with multiple myeloma. Biol Blood Marrow Transplant 2000; 6: 375–386.

    Article  CAS  Google Scholar 

  26. Shimoni A, Gajewski JA, Donato M et al. Long-term follow-up of recipients of CD8-depleted donor lymphocyte infusions for the treatment of chronic myelogenous leukemia relapsing after allogeneic progenitor cell transplantation. Biol Blood Marrow Transplant 2001; 7: 568–575.

    Article  CAS  Google Scholar 

  27. Soiffer RJ, Alyea EP, Hochberg E et al. Randomized trial of CD8+ T-cell depletion in the prevention of graft-versus-host disease associated with donor lymphocyte infusion. Biol Blood Marrow Transplant 2002; 8: 625–632.

    Article  Google Scholar 

  28. Kobbe G, Schneider P, Aivado M et al. Reliable engraftment, low toxicity, and durable remissions following allogeneic blood stem cell transplantation with minimal conditioning. Exp Hematol 2002; 30: 1346–1353.

    Article  Google Scholar 

  29. Antin JH, Childs R, Filipovich AH et al. Establishment of complete and mixed donor chimerism after allogeneic lymphohematopoietic transplantation: recommendations from a workshop at the 2001 tandem meetings. Biol Blood Marrow Transplant 2001; 7: 473–485.

    Article  CAS  Google Scholar 

  30. 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  Google Scholar 

Download references

Acknowledgements

Frédéric Baron is Research Assistant and Yves Beguin Research Director of the National Fund for Scientific Research (FNRS, Belgium). This work was supported by grants from ‘La Fondation Bonjean- Oleffe’, ‘L'Association sportive contre le Cancer’, ‘Le Fonds de Recherche Scientifique du CHU Sart-Tilman’ and the National Fund for Scientific Research (FNRS, Belgium).

Author information

Authors and Affiliations

  1. Department of Medicine, Division of Hematology, University of Liège, Liège, Belgium

    F Baron, E Baudoux, P Frère, G Fillet & Y Beguin

  2. Department of Transfusion Medicine, University of Liège, Liège, Belgium

    S Tourqui

  3. Department of Clinical Biology, Division of Laboratory Hematology, University of Liège, Liège, Belgium

    N Schaaf-Lafontaine

  4. Department of Genetics, University of Liège, Liège, Belgium

    C Herens

  5. Department of Hematology, Centre Hospitalier Regional La Citadelle, University of Liège, Liège, Belgium

    B DePrijck

Authors
  1. F Baron
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E Baudoux
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P Frère
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S Tourqui
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. N Schaaf-Lafontaine
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. C Herens
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. B DePrijck
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. G Fillet
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Y Beguin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to F Baron.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Baron, F., Baudoux, E., Frère, P. et al. Low T-cell chimerism is not followed by graft rejection after nonmyeloablative stem cell transplantation (NMSCT) with CD34-selected PBSC. Bone Marrow Transplant 32, 829–834 (2003). https://doi.org/10.1038/sj.bmt.1704220

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1704220

Keywords

This article is cited by

Search

Advanced search

Quick links