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Donor leukocyte infusions in acute myelogenous leukemia

Leukemia volume 17, pages 1035–1037 (2003)Cite this article

The success of allogeneic stem cell transplantation (SCT) is dependent not only on the intensive conditioning therapy, but also on the graft-versus-leukemia (GVL) properties of the donor graft. Unfortunately, despite recent advances, disease relapse remains a major obstacle to successful transplant in patients with acute myeloid leukemia (AML). Patients transplanted in first remission have a 10–20% relapse rate and those with more advanced disease have relapse rates of 40–60%. The treatment options for relapse have generally been limited. Second SCT may cure a minority of these patients but at the expense of extensive morbidity and mortality. A safer and more effective approach to relapse is needed. One such approach is the use of donor leukocyte infusions (DLI) to induce a direct GVL reaction for patients with relapsed AML without the need for additional myeloablative conditioning therapy.

Kolb et al1 first published the effective use of DLI in three patients with relapsed chronic myelogenous leukemia (CML) who all had a complete cytogenetic remission. Subsequent studies have confirmed that DLI is dramatically effective for patients with CML. In all, 70–80% of chronic phase CML patients treated with DLI achieve a complete cytogenetic response,2,3 and the majority of these patients achieve a molecular remission as well. DLI has been much less effective for patients with acute leukemia. Retrospective data, compiled from two large registries (the North American registry and the European Group for Blood and Marrow Transplantation) indicate that response rates to DLI for relapsed AML range from 15 to 30%.2,3 Response rates in acute lymphoblastic leukemia (ALL) are even lower, at about 10%.

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References

  1. Kolb H, Mittermuller J, Clemm C, Holler E, Ledderose G, Brehm G et al. Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Blood 1990; 76: 2462–2465.

    CAS  PubMed  Google Scholar 

  2. Kolb H, Schattenberg A, Goldman J, Hertenstein B, Jacobsen N, Arcese W et al. Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. Blood 1995; 86: 2041–2050.

    CAS  PubMed  Google Scholar 

  3. Collins R, Shpilberg O, Drobyski W, Porter D, Giralt S, Champlin R 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 

  4. Porter D, Collins R, Shpilberg O, Drobyski W, Connors J, Sproles A et al. Long-term follow-up of patients who achieved complete remission after donor leukocyte infusions. Biol Blood Marrow Transplant 1999; 5: 253–261.

    Article  CAS  PubMed  Google Scholar 

  5. Porter D, Collins R, Hardy C, Kernan N, Drobyski W, Giralt S et al. Treatment of relapsed leukemia after unrelated donor marrow transplantation with unrelated donor leukocyte infusions. Blood 2000; 95: 1214–1221.

    CAS  PubMed  Google Scholar 

  6. Leis J, Porter D . Unrelated donor leukocyte infusions to treat relapse after unrelated donor bone marrow transplantation. Leukemia Lymphoma 2002; 43: 9–17.

    Article  PubMed  Google Scholar 

  7. Levine J, Braun T, Penza S, Beatty P, Cornetta K, Martino R et al. Prospective trial of chemotherapy and donor leukocyte infusions for relapse of advanced myeloid malignancies after allogeneic stem cell transplantation. J Clin Oncol 2001; 20: 405–412.

    Article  Google Scholar 

  8. 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  PubMed  Google Scholar 

  9. Naparsteck E, Or R, Nagler A, Cividalli G, Engelhard D, Aker M et al. T-cell-depleted allogeneic bone marrow transplantation for acute leukaemia using Campath-1 antibodies and post-transplant administration of donor's peripheral blood lymphocytes for prevention of relapse. Br J Haematol 1995; 89: 506–515.

    Article  Google Scholar 

  10. Barrett AJ, Mavroudis D, Tisdale J, Molldrem J, Clave E, Dunbar C et al. T cell-depleted bone marrow transplantation and delayed T cell add-back to control acute GVHD and conserve a graft-versus-leukemia effect. Bone Marrow Transplantation 1998; 21: 543–551.

    Article  CAS  PubMed  Google Scholar 

  11. Schaap N, Schattenberg A, Bar B, Preijers F, van de Wiel van Kemenade E et al. Induction of graft-versus-leukemia to prevent relapse after partially lymphocyte-depleted allogeneic bone marrow transplantation by pre-emptive donor leukocyte infusions. Leukemia 2001; 15: 1339–1346.

    Article  CAS  PubMed  Google Scholar 

  12. Mackinnon S, Papadopoulos E, Carabasi M, Reich L, Collins N, Boulad F 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 1995; 86: 1261–1268.

    CAS  PubMed  Google Scholar 

  13. Alyea E, Soiffer R, Canning C, Neuberg D, Schlossman R, Pickett 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 

  14. Giralt S, Hester J, Huh Y, Hirsch-Ginsberg C, Rondon G, Seong D et al. CD8-depleted donor lymphocyte infusion as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation. Blood 1995; 86: 4337–4343.

    CAS  PubMed  Google Scholar 

  15. Waller EK, Boyer M . New strategies in allogeneic stem cell transplantation: immunotherapy using irradiated allogeneic T cells. Bone Marrow Transplant 2000; 25: S20–S24.

    Article  PubMed  Google Scholar 

  16. Bonini C, Ferrari G, Verzeletti S, Servida P, Zappone E, Ruggieri L et al. HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia. Science 1997; 276: 1719–1724.

    Article  CAS  PubMed  Google Scholar 

  17. Bocchia M, Korontsvit T, Xu Q, Mackinnon S, Yang SY, Sette A et al. Specific human cellular immunity to bcr-abl oncogene derived peptides. Blood 1996; 87: 3587–3592.

    CAS  PubMed  Google Scholar 

  18. Molldrem JJ, Lee PP, Wang C, Felio K, Kantarjian HM, Champlin RE et al. Evidence that specific T lymphocytes may participate in the elimination of chronic myelogenous leukemia. Nat Med 2000; 6: 1018–1023.

    Article  CAS  PubMed  Google Scholar 

  19. Falkenburg JH, Smit WM, Willemze R . Cytotoxic T-lymphocyte (CTL) responses against acute or chronic myeloid leukemia. Immunol Rev 1997; 157: 223–230.

    Article  CAS  PubMed  Google Scholar 

  20. Kircher B, Stevanovic S, Urbanek M, Mitterschiffthaler A, Rammensee H, Brunewald K et al. Induction of HA-1-specific cytotoxic T-cell clones parallels the therapeutic effect of donor lymphocyte infusion. Br J Haematol 2002; 117: 935–939.

    Article  PubMed  Google Scholar 

  21. Mutis T, Verdijk R, Schrama E, Esendam B, Brand A, Goulmy E . Feasibility of immunotherapy of relapsed leukemia with ex vivo-generated cytotoxic T lymphocytes specific for hematopoietic system-restricted minor histocompatibility antigens. Blood 1999; 93: 2336–2341.

    CAS  PubMed  Google Scholar 

  22. Slavin S, Naparstek E, Nagler A, Ackerstein A, Samuel S, Kapelushnik J et al. Allogeneic cell therapy with donor peripheral blood cells and recombinant human interleukin-2 to treat leukemia relapse after allogeneic bone marrow transplantation. Blood 1996; 87: 2195–2204.

    CAS  PubMed  Google Scholar 

  23. Laport G, Liebowitz D, Williams S, Zimmerman T, Felix C, Stadtmauer E et al. Adoptive transfer of CD3/CD28 ex vivo co-stimulated T cell in patients with relapsed/refractory non-Hodgkin's lymphoma (NHL) following high dose chemotherapy (HDC) with CD34-selected peripheral blood stem cells (PBSC) support. Blood 2000; 96: 407a.

    Google Scholar 

  24. Porter D, Bunin N, Laport G, Duffy K, Bennett P, Than T et al. Graft-vs-tumor induction with donor leukocyte infusions expanded ex-vivo by activation with CD3/CD28 costimulation. Blood 2001; 98: 404a.

    Google Scholar 

  25. Porter D, Connors J, VanDeerlin V, Duffy K, McGarigle C, Saidman S et al. Graft-versus-tumor induction with donor leukocyte infusions as primary therapy for patients with malignancies. J Clin Oncol 1999; 17: 1234–1243.

    Article  CAS  PubMed  Google Scholar 

  26. Khouri I, Keating M, Korbling M, Przepiorka D, Anderlini P, O'Brien S et al. Transplant-lite: induction of graft-vs-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment for lymphoid malignancies. J Clin Oncol 1998; 16: 2817–2824.

    Article  CAS  PubMed  Google Scholar 

  27. Giralt S, Estey E, Albitar M, van Besien K, Rondon G, Anderlini P et al. Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. Blood 1997; 89: 4531–4536.

    CAS  PubMed  Google Scholar 

  28. Slavin S, Nagler A, Naparstek E, Kapelushnik Y, Aker M, Cividalli G et al. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood 1998; 91: 756–763.

    CAS  PubMed  Google Scholar 

  29. Porter D, Luger S, Duffy K, Stadtmauer E, Laport G, Schuster S et al. Allogeneic cell therapy for patients who relapse after autologous stem cell transplantation. Biol of Blood and Marrow Transplant 2001; 7: 230–238.

    Article  CAS  Google Scholar 

  30. Devine SM, Sanborn R, Jessop E, Stock W, Huml M, Peace D et al. Fludarabine and melphalan-based conditioning for patients with advanced hematological malignancies relapsing after a previous hematopoietic stem cell transplant. Bone Marrow Transplantation 2001; 28: 557–562.

    Article  CAS  PubMed  Google Scholar 

  31. Schlenk RF, Hartmann F, Hensel M, Jung W, Weber-Nordt R, Gabler A et al. Less intense conditioning with fludarabine, cyclophosphamide, idarubicin and etoposide (FCIE) followed by allogeneic unselected peripheral blood stem cell transplantation in elderly patients with leukemia. Leukemia 2002; 16: 581–586.

    Article  CAS  PubMed  Google Scholar 

  32. Bornhauser M, Thiede C, Schuler U, Platzbecker U, Freiberg-Richter J, Helwig A et al. Dose-reduced conditioning for allogeneic blood stem cell transplantation: durable engraftment without anti thymocyte globulin. Bone Marrow Transplant 2000; 26: 119–125.

    Article  CAS  PubMed  Google Scholar 

  33. McSweeney PA, Niederwieser D, Shizuru JA, Sandmaier BM, Molina AJ, Maloney DG 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  PubMed  Google Scholar 

  34. Arnold R, Massenkeil G, Bornhauser M, Ehninger G, Beelen DW, Fauser AA et al. Nonmyeloablative stem cell transplantation in adults with high-risk ALL may be effective in early but not in advanced disease. Leukemia 2002; 16: 2423–2428.

    Article  CAS  PubMed  Google Scholar 

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  1. Bone Marrow and Stem Cell Transplant Program, University of Pennsylvania Medical Center, Philadelphia, PA, USA

    D L Porter

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Porter, D. Donor leukocyte infusions in acute myelogenous leukemia. Leukemia 17, 1035–1037 (2003). https://doi.org/10.1038/sj.leu.2402950

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