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:

Donor Lymphocyte Infusions

Factors predicting response and graft-versus-host disease after donor lymphocyte infusions: a study on 593 infusions

Summary:

In the present study, we analyze factors predicting graft-versus-host disease (GvHD) and response after donor lymphocyte infusions (DLI). A total of 100 patients received 593 DLI between June 1990 and December 2000 in a bulk dose (n=14) or in escalating dose infusions (n=86). Patients were analyzed after stratification for type of relapse: (1) molecular relapse (n=6), (2) cytogenetic relapse (n=20), (3) chronic phase of chronic myeloid leukemia (CML) or complete remission of other disease post chemotherapy (n=24), (4) CML in accele-rated/blastic phase (n=14), (5) resistant disease not responding to chemotherapy (n=36). The proportion of responders to DLI in these five groups was 100, 90, 75, 36 and 0% (P<0.0001). Factors predicting response by multivariate analysis were type of relapse (P<0.0001), post-DLI GvHD (P=0.005), pancytopenia (P=0.008), and a diagnosis of CML (P=0.04). Acute GvHD (grades II—IV) occurred in 21 patients (21%), and correlated in multivariate analysis with pancytopenia and less than four DLI. Other predictors of GvHD were the number of CD3+cells/infusion and serum levels of gamma-glutamyl transferase (γGT). The actuarial probability of treatment-related mortality was 9% for HLA identical siblings and 44% for alternative donor transplants (P=0.006). Response to DLI is predicted by tumor burden and is associated with GvHD and pancytopenia.

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

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

References

  1. Goldman JM, Gale RP, Horowitz MM et al. Bone marrow transplantation for the treatment of chronic myelogenous leukemia in chronic phase. Ann Intern Med 1988; 108: 806–814.

    Article  CAS  PubMed  Google Scholar 

  2. Reiter E, Greinix HT, Brugger S et al. Long term follow up after allogeneic stem cell transplantation for chronic myelogenous leukemia. Bone Marrow Transplant 1998; 22: S86–S88.

    PubMed  Google Scholar 

  3. Gorin NC, Labopin M, Fouillard L et al. Retrospective evaluation of autologous bone marrow transplantation vs allogeneic bone marrow transplantation from an HLA identical related donor in acute myelocytic leukemia. A study of the European Cooperative Group for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant 1996; 18: 111–117.

    CAS  PubMed  Google Scholar 

  4. Weiden PL, Flournoy N, Thomas ED et al. Antileukemic effect of graft versus host disease in human recipient of allogeneic marrow grafts. N Engl J Med 1979; 300: 1068–1073.

    Article  CAS  PubMed  Google Scholar 

  5. Marmont AM, Horowitz MM, Gale RP et al. T-cell depletion of HLA-identical transplants in leukemia. Blood 1991; 78: 2120–2130.

    CAS  PubMed  Google Scholar 

  6. Locatelli F, Zecca M, Rondelli et al. Graft versus host disease prophylaxis with low dose cyclosporine reduces the risk of relapse in children with acute leukemia given HLA identical sibling bone marrow transplantation: results of a randomized trial. Blood 2000; 95: 1572–1579.

    CAS  PubMed  Google Scholar 

  7. Zikos P, van Lint MT, Lamparelli T et al. Allogeneic hemopoietic stem cell transplantation for patients with high risk acute lymphoblastic leukemia: favorable impact of chronic graft-versus-host disease on survival and relapse. Haematologica 1998; 83: 896–903.

    CAS  PubMed  Google Scholar 

  8. Kolb HJ, Schattenberg A, Goldman JM et al. Graft versus leukemia effect of donor lymphocyte transfusions in marrow grafted patients. Blood 1995; 86: 2041–2050.

    CAS  PubMed  Google Scholar 

  9. Kolb HJ . Relapse. The EBMT Handbook. Blood Marrow Transplant 2000; 1: 200–215.

    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 1997; 15: 433–444.

    Article  PubMed  Google Scholar 

  11. 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: 253–261.

    Article  CAS  PubMed  Google Scholar 

  12. Slavin S, Naparstek E, Nagler A et al. 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 

  13. Frassoni F, Podestà M, Piaggio G et al. Relapse after allogeneic BMT for chronic myeloid leukemia (CML) may be sustained by a small number of leukemic ‘stem cells’: a hypothesis. Bone Marrow Transplant 1999; 24: 689–691.

    Article  CAS  PubMed  Google Scholar 

  14. Champlin R, Khouri I, Kornablau S et al. Allogeneic hematopoietic transplantation as adoptive immunotherapy. Hematopoietic Stem Cell Ther 1999; 13: 1041–1057.

    CAS  Google Scholar 

  15. Dazzi F, Szylo 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 

  16. 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 responses from graft versus host disease. Blood 1994; 86: 1261–1268.

    Google Scholar 

  17. 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 

  18. Keil F, Haas OA, Fritsch G et al. Donor leukocyte infusion for leukemic relapse after allogeneic marrow transplantation: lack of residual donor hematopoiesis predicts aplasia. Blood 1997; 89: 3113–3117.

    CAS  PubMed  Google Scholar 

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

    Article  Google Scholar 

  20. Schafer H, Bader P, Kaiserling E et al. Extramedullary relapses at uncommon sites after allogeneic stem cell transplantation. Bone Marrow Transplant 2000; 26: 1133–1134.

    Article  CAS  PubMed  Google Scholar 

  21. Au WY, Lie AKW, Liang R et al. Isolated extramedullary relapse of acute lymphoblastic leukemia after allogeneic bone marrow transplantation. Bone Marrow Transplant 1999; 24: 1137–1140.

    Article  CAS  PubMed  Google Scholar 

  22. Goldberg SL, Mangan KF, Klumpp TR et al. Lack of graft versus leukemia effect in an immunologically privileged site (letter). Bone Marrow Transplant 1994; 14: 180–181.

    CAS  PubMed  Google Scholar 

  23. Seo S, Kami M, Honda H et al. Extramedullary relapse in the so-called ‘sanctuary’ sites for chemotherapy after donor lymphocyte infusion (letter). Bone Marrow Transplant 2000; 25: 226–227.

    Article  CAS  PubMed  Google Scholar 

  24. Lokhorst HM, Schattenberg A, Cornelissen JJ et al. Donor lymphocyte infusions for relapsed multiple myeloma after allogenic stem-cell transplantation: predictive factors for response and long-term outcome. J Clin Oncol 2000; 18: 3031–3037.

    Article  CAS  PubMed  Google Scholar 

  25. Orsini E, Aleya 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  PubMed  Google Scholar 

  26. Sprent J, Surh CD, Agus D et al. Profound atrophy of the bone marrow reflecting major histocompatibility complex class II-restricted destruction of stem cells by CD4+cells. J Exp Med 1994; 180: 307–317.

    Article  CAS  PubMed  Google Scholar 

  27. Dominietto A, Raiola AM, van Lint Mt et al. Factors influencing hematologic recovery after allogeneic hemopoietic stem cells transplant (HSCT): graft versus host disease, donor type, cytomegalovirus infections and cell dose. Br J Haematol 2000; 112: 219–227.

    Article  Google Scholar 

  28. Glucksberg H, Storb R, Fefer A et al. Clinical manifestations of graft versus host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation 1974; 18:295–304.

    Article  CAS  PubMed  Google Scholar 

  29. Sullivan K, Weiden P, Storb R et al. Influence of acute and chronic graft-versus-host disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukaemia. Blood 1989; 73: 1720–1728.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  31. Alyea EP, Soiffer RJ, Canning C et al. Toxicity and efficacy of defined doses of CD4+donor lymphocytes for treatment of relapse after allogeneic bone marrow transplant. Blood 1998; 91: 3671–3680.

    CAS  PubMed  Google Scholar 

  32. 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 

Download references

Acknowledgements

This work was supported by Associazione Italiana Ricerca contro il Cancro (AIRC) Milano grant to AB and Associazione Ricerca Trapianto Midollo Osseo (ARITMO) Genova. The great work of our nursing staff is gratefully acknowledged.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Raiola, A., Van Lint, M., Valbonesi, M. et al. Factors predicting response and graft-versus-host disease after donor lymphocyte infusions: a study on 593 infusions. Bone Marrow Transplant 31, 687–693 (2003). https://doi.org/10.1038/sj.bmt.1703883

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1703883

Keywords

This article is cited by

Search

Quick links