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:

Post-Transplant Events

Outcome and long-term follow-up of alloreactive donor lymphocyte infusions given for relapse after myeloablative allogeneic hematopoietic stem cell transplantations (HSCT)

Bone Marrow Transplantation volume 35, pages 601–608 (2005)Cite this article

Summary:

In order to study efficacy, toxicity and the long-term results of donor lymphocyte infusions (DLI), we retrospectively analyzed DLI given for relapse after conventional allogeneic hematopoietic stem cell transplantation (HSCT) in 30 patients with a median delay of 107.5 months after transplant and 58 months after DLI. After DLI, 15 patients established full donor chimerism, three patients developed grade III and one grade IV acute GVHD. A total of 15 patients achieved a disease response. Among the 14 patients with chronic myeloid leukemia (CML), 11 are alive at the last follow-up: five are in complete molecular response (CMR) and two in complete cytogenetic response (CCR) with no other intervention after DLI, three in CMR after imatinib mesylate given after DLI and one in complete hematological response after imatinib mesylate and reduced-intensity conditioning allogeneic SCT performed after DLI. At the time of the last follow-up, 19 (63%) patients died and 11 (37%) remain alive. The 3-year probability of survival for the entire population, CML patients and non-CML patients, was 60, 93, 62% after transplantation, and 48, 80 and 48% after DLI, respectively. A multivariate analysis demonstrated a significantly worse survival rate after transplantation for female recipients, advanced disease and acute leukemia before transplantation.

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
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Dazzi F, Goldman JM . Donor leukocyte infusions. Curr Opin Hematol 1999; 6: 394–399.

    Article  CAS  PubMed  Google Scholar 

  2. Michallet M, Tanguy ML, Socie G et al. Second allogeneic hematopoietic stem cell transplantation in relapsed acute and chronic leukemias for patients who underwent a first allogeneic bone marrow transplantation: a survey of the Societe Francaise de Greffe de Moelle (SFGM). Br J Hematol 2000; 108: 400–407.

    Article  CAS  Google Scholar 

  3. Higano CS, Chielens D, Raskind W et al. Use of alpha-2a-interferon to treat cytogenetic relapse of chronic myeloid leukemia after marrow transplantation. Blood 1997; 9: 2549–2554.

    Google Scholar 

  4. Kolb HJ, Mittermuller J, Clemm C et al. Donor leukocyte transfusions for treatment of recurrent chronic myelogeneous leukemia after marrow transplantation. Blood 1990; 76: 2462–2465.

    CAS  PubMed  Google Scholar 

  5. Goldman JM, Melo JV . Targeting the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 2001; 344: 1084–1086.

    Article  CAS  PubMed  Google Scholar 

  6. Porter DL, Connors JM, Van Deerlin VM et al. Graft-versus-tumor induction with donor leukocyte infusions as primary therapy for patients with malignancies. J Clin Oncol 1999; 17: 1234.

    Article  CAS  PubMed  Google Scholar 

  7. Dazzi F, Szydlo RM, Goldman JM . Donor lymphocyte infusions for relapse of chronic myeloid leukemia after allogeneic stem cell transplant: where we now stand. Exp Hematol 1999; 27: 1477–1486.

    Article  CAS  PubMed  Google Scholar 

  8. Van Rhee F, Lin F, Cullis JO et al. Relapse of chronic myeloid leukemia after allogeneic bone marrow transplant: the case for giving donor leukocyte transfusions before the onset of hematologic relapse. Blood 1994; 83: 3377–3383.

    CAS  PubMed  Google Scholar 

  9. Bacigalupo A, Soracco M, Vassallo F et al. Donor lymphocyte infusions in patients with chronic myeloid leukemia following allogeneic bone marrow transplantation. Bone Marrow Transplant 1997; 19: 927–932.

    Article  CAS  PubMed  Google Scholar 

  10. Collins RH, Shpilberg O, Drobyski WR et al. Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation. J Clin Oncol 1999; 15: 433–444.

    Article  Google Scholar 

  11. Storb R . Nonmyeloablative hematopoietic stem cell transplantation: replacing cytotoxic therapy by the graft-versus-tumor effect. Ann NY Acad Sci 2001; 938: 328–337.

    PubMed  Google Scholar 

  12. Michallet M, Bilger K, Garban F et al. Allogeneic hematopoietic stem-cell transplantation after non-myeloablative preparative regimens: impact of pretransplantation and posttransplantation factors on outcome. J Clin Oncol 2001; 19: 3340–3349.

    Article  CAS  PubMed  Google Scholar 

  13. Drobyski W, Keever C, Roth MS et al. Salvage immunotherapy using donor leukocyte infusions as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation: efficacy and toxicity of a defined T-cell dose. Blood 1993; 82: 2310–2318.

    CAS  PubMed  Google Scholar 

  14. Mackinnon S, Papadopulos EB, Carabasi MH et al. Adoptive immunotherapy evaluating escalating doses of donor leukocytes for relapse of chronic myeloid leukemia after bone marrow transplantation: separation of graft versus leukemia from graft versus host disease. Blood 1994; 86: 1261–1268.

    Google Scholar 

  15. Dazzi F, Szydlo RM, Craddock C et al. Comparison of single dose and escalating dose regimens of donor lymphocyte infusion for relapse after allografting for chronic myeloid leukemia. Blood 2000; 95: 67–71.

    CAS  PubMed  Google Scholar 

  16. Giralt S, Hester J, Huh Y et al. CD8-depleted donor lymphocyte infusion as treatment for relapsed chronic myelogeneous leukemia after allogeneic bone marrow transplantation. Blood 1995; 86: 4337–4443.

    CAS  PubMed  Google Scholar 

  17. Porter DL, Collins RH, Shpilberg O et al. Long-term follow-up of patients who achieved complete remission after donor leukocyte infusion. Biol Blood Marrow Transplant 1999; 5: 252–261.

    Article  Google Scholar 

  18. Mattei D, Saglio G, Gottardi E et al. Persistent molecular remission ten years after donor lymphocyte infusion for hematologic relapse in chronic myeloid leukemia. Haematologica 2001; 86: 545–546.

    CAS  PubMed  Google Scholar 

  19. Dazzi F, Szydlo RM, Cross NC 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. 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; 29: 1055–1060.

    Article  Google Scholar 

  21. Fefer A, Robinson N, Benyunes MC et al. Interleukin-2 therapy after bone marrow or stem cell transplantation for hematologic malignancies. Cancer J Sci Am 1997; 1: 35–36.

    Google Scholar 

  22. Robinson N, Benyunes MC, Thompson JA et al. Interleukin-2 after autologous stem cell transplantation for hematologic malignancy: a phase I/II study. Bone Marrow Transplant 1997; 19: 435–442.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Powles R, Smith C, Milan S et al. Human recombinant GM-CSF in allogeneic bone marrow transplantation for leukemia: double bind, placebo-control trial. Lancet 1990; 336: 1417–1420.

    Article  CAS  PubMed  Google Scholar 

  24. Gupta P, Tiley C, Powles R et al. No increase in relapse in patients with myeloid leukemias receiving rhGM-CSF after allogeneic bone marrow transplantation. Bone Marrow Transplant 1992; 6: 491–493.

    Google Scholar 

  25. Singhal S, Powles R, Treleaven J et al. Long-term safety of GM-CSF (molgrastim) administration after allogeneic bone marrow transplantation for hematological malignancies: five-year follow-up of a double-blind randomized placebo controlled study. Leukemi Lymphoma 1997; 24: 301–307.

    Article  CAS  Google Scholar 

  26. Olavarria E, Ottmann OG, Deininger M et al. Response to imatinib in patients who relapse after allogeneic stem cell transplantation for chronic myeloid leukemia. Leukemia 2003; 17: 1707–1712.

    Article  CAS  PubMed  Google Scholar 

  27. Zwaan CM, Reinhardt D, Corbacioglu S et al. Gemtuzumab ozogamicin: first clinical experiences in children with relapsed/refractory acute myeloid leukemia treated on compassionate-use basis. Blood 2003; 101: 3868–3871.

    Article  CAS  PubMed  Google Scholar 

  28. Shimoni A, Hardan I, Avigdor A et al. Rituximab reduces relapse risk after allogeneic and autologous stem cell transplantation in patients with high-risk aggressive non-Hodgkin's lymphoma. Br J Haematol 2003; 122: 457–464.

    Article  CAS  PubMed  Google Scholar 

  29. Kolb HJ, Holler E . Adoptive immunotherapy with donor lymphocyte transfusions. Curr Opin Oncol 1997; 9: 139–145.

    Article  CAS  PubMed  Google Scholar 

  30. Kolb HJ, Schattenberg A, Goldman JM et al. Graft-versus-leukemia effect of donor lymphocytes 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 

  31. Carlens S, Remberger M, Aschan J, Ringden O . The role of disease stage in response to donor lymphocyte infusions as treatment for leukemic relapse. Biol Blood Marrow Transplant 2000; 7: 31–38.

    Article  Google Scholar 

  32. Guglielmi C, Arcese W, Dazzi F et al. Donor lymphocyte infusion for relapsed chronic myelogenous leukemia: prognostic relevance of the initial cell dose. Blood 2002; 100: 397–405.

    Article  CAS  PubMed  Google Scholar 

  33. Raiola AM, Van Lint MT, Valbonesi M et al. Factors predicting response and graft-versus-host disease after donor lymphocyte infusions: a study on 593 infusions. Bone Marrow Transplant 2003; 31: 687–693.

    Article  CAS  PubMed  Google Scholar 

  34. McCann SR, Gately K, Conneally E, Lawler M . Molecular response to imatinib mesylate following relapse allogeneic SCT for CML. Blood 2003; 101: 1200–1201.

    Article  CAS  PubMed  Google Scholar 

  35. Vela-Ojeda J, Garcia-Ruiz Esparza MA, Reyes-Maldonado E et al. Donor lymphocyte infusions for relapse of chronic myeloid leukemia after allogeneic stem cell transplantation : prognostic significance of the dose of CD3(+) and CD4(+) lymphocytes. Ann Hematol 2004; 83: 295–301.

    Article  CAS  PubMed  Google Scholar 

  36. Shimoni A, Kroger N, Zander AR et al. Imatinib mesylate (STI571) in preparation for allogeneic stem cell transplantation and donor lymphocyte infusions in patients with Philadelphia-positive acute leukemias. Leukemia 2003; 17: 290–297.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the Unité de Recherche Clinique (URC) (pavillon E, Hôpital Edouard-Herriot, Lyon).

Author information

Authors and Affiliations

  1. Service d’Hématologie Clinique, Hôpital Edouard Herriot, Lyon cedex, France

    A S Michallet, F Nicolini, S Fürst, Q H Le, X Thomas & M Michallet

  2. Laboratoire d’histocompatibilité, Etablissement Français du Sang, Lyon, France

    V Dubois & L Gebuhrer

  3. Laboratoire d’Hématologie, Hôpital Edouard Herriot, Lyon cedex, France

    S Hayette

  4. Banque de cellules et de tissus, Etablissement Français du Sang, Hôpital Edouard Herriot, Lyon cedex, France

    J P Bourgeot & J P Tremisi

Authors
  1. A S Michallet
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F Nicolini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S Fürst
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Q H Le
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. V Dubois
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S Hayette
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. J P Bourgeot
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. J P Tremisi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. X Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. L Gebuhrer
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. M Michallet
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A S Michallet.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Michallet, A., Nicolini, F., Fürst, S. et al. Outcome and long-term follow-up of alloreactive donor lymphocyte infusions given for relapse after myeloablative allogeneic hematopoietic stem cell transplantations (HSCT). Bone Marrow Transplant 35, 601–608 (2005). https://doi.org/10.1038/sj.bmt.1704807

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1704807

Keywords

This article is cited by

Search

Advanced search

Quick links