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.

  • Review
  • Published:

Donor leukocyte infusions for the treatment of relapsed acute leukemia after allogeneic stem cell transplantation

Abstract

Allogeneic stem cell transplantation (SCT) offers the only hope for cure for many adults with acute leukemia. Unfortunately, many patients relapse and die of their disease even after transplantation. Although in some cases, allogeneic SCT is effective because the intensive conditioning therapy eradicates all malignant cells, it has long been recognized that the adoptive transfer of donor immunity plays a critically important role in the induction and maintenance of remission. Recognition of the graft-versus-leukemia (GVL) effect of allogeneic SCT has prompted attempts at remission re-induction by adoptive immunotherapy with donor lymphocyte infusions (DLIs) in patients with relapsed disease after allogeneic SCT. In some cases, DLI-induced remissions are sustained and patients cured when no other treatment modality was effective. This review discusses the rationale, biology, complications and future applications of DLI in acute leukemia patients after allogeneic SCT.

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

Similar content being viewed by others

References

  1. Barnes D, Corp M, Loutit J, Neal F . Treatment of murine leukaemia with X rays and homologous bone marrow. Preliminary communication. Br Med J 1956; 2: 626–630.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Barnes D, Loutit J . Treatment of murine leukaemia with X-rays and homologous bone marrow. Br J Haematol 1957; 3: 241–252.

    CAS  PubMed  Google Scholar 

  3. Mathe G, Amiel J, Schwarzenberg L, Cattan A, Schneider M . Adoptive immunotherapy of acute leukemia: experimental and clinical results. Cancer Res 1965; 25: 1525–1531.

    CAS  PubMed  Google Scholar 

  4. Weiden P, Flournoy N, Donnall Thomas E, Prentice R, Fefer A, Buckner C et al. Antileukemic effect of graft-versus-host disease in human recipients of allogeneic-marrow grafts. N Engl J Med 1979; 300: 1068–1073.

    CAS  PubMed  Google Scholar 

  5. Horowitz M, Gale R, Sondel P, Goldman J, Kersey J, Kolb H et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood 1990; 75: 555–562.

    CAS  PubMed  Google Scholar 

  6. Gale R, Horowitz M, Ash R, Champlin R, Goldman J, Rimm A et al. Identical-twin bone marrow transplants for leukemia. Ann Int Med 1994; 120: 646–652.

    CAS  PubMed  Google Scholar 

  7. 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 

  8. Porter D, Roth M, McGarigle C, Ferrara J, Antin J . Induction of graft-versus-host disease as immunotherapy for relapsed chronic myeloid leukemia. N Engl J Med 1994; 330: 100–106.

    CAS  PubMed  Google Scholar 

  9. 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.

    PubMed  Google Scholar 

  10. 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 

  11. Drobyski W, Keever C, Roth M, Koethe S, Hanson G, McFadden P 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 

  12. 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.

    CAS  PubMed  Google Scholar 

  13. Dazzi F, Szydlo RM, Cross NC, Craddock C, Kaeda J, Kanfer E 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 

  14. Porter D, Roth M, Lee S, McGarigle C, Ferrara J, Antin J . Adoptive immunotherapy with donor mononuclear cell infusions to treat relapse of acute leukemia or myelodysplasia after allogeneic bone marrow transplantation. Bone Marrow Transplant 1996; 18: 975–980.

    CAS  PubMed  Google Scholar 

  15. 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 

  16. Szer J, Grigg A, Phillipos G, Sheridan W . Donor leucocyte infusions after chemotherapy for patients relapsing with acute leukaemia following allogeneic BMT. Bone Marrow Transplant 1993; 11: 109–111.

    CAS  PubMed  Google Scholar 

  17. Shiobara S, Nakao S, Ueda M, Yamazaki H, Takahashi S, Asano S et al. Donor leukocyte infusion for Japanese patients with relapsed leukemia after allogeneic bone marrow transplantation: lower incidence of acute graft-versus-host disease and improved outcome. Bone Marrow Transplant 2000; 26: 769–774.

    CAS  PubMed  Google Scholar 

  18. Choi SJ, Lee JH, Kim S, Seol M, Lee YS, Lee JS et al. Treatment of relapsed acute myeloid leukemia after allogeneic bone marrow transplantation with chemotherapy followed by G-CSF-primed donor leukocyte infusion: a high incidence of isolated extramedullary relapse. Leukemia 2004; 18: 1789–1797.

    CAS  PubMed  Google Scholar 

  19. Collins Jr RH, Goldstein S, Giralt S, Levine J, Porter D, Drobyski W et al. Donor leukocyte infusions in acute lymphocytic leukemia. Bone Marrow Transplant 2000; 26: 511–516.

    PubMed  Google Scholar 

  20. 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 2002; 20: 405–412.

    CAS  PubMed  Google Scholar 

  21. Cunningham I . Extramedullary sites of leukemia relapse after transplant. Leuk Lymphoma 2007; 47: 1754–1767.

    Google Scholar 

  22. Singhal S, Powles R, Kulkarni S, Treleaven J, Saso R, Mehta J . Long-term follow-up of relapsed acute leukemia treated with immunotherapy after allogeneic transplantation: the inseparability of graft-versus-host disease and graft-versus-leukemia, and the problem of extramedullary relapse. Leuk Lymphoma 1999; 32: 505–512.

    CAS  PubMed  Google Scholar 

  23. Berthou C, Leglise MC, Herry A, Balcon D, Hardy E, Lessard M et al. Extramedullary relapse after favorable molecular response to donor leukocyte infusions for recurring acute leukemia. Leukemia 1998; 12: 1676–1681.

    CAS  PubMed  Google Scholar 

  24. Chong G, Byrnes G, Szer J, Grigg A . Extramedullary relapse after allogeneic bone marrow transplantation for haematological malignancy. Bone Marrow Transplant 1011; 26: 1011–1015.

    Google Scholar 

  25. Slavin S, Morecki S, Weiss L, Or R . Donor lymphocyte infusion: the use of alloreactive and tumor-reactive lymphocytes for immunotherapy of malignant and nonmalignant diseases in conjunction with allogeneic stem cell transplantation. Hematother Stem Cell Res 2002; 11: 265–276.

    Google Scholar 

  26. Choi SJ, Lee JH, Kim S, Lee YS, Seol M, Ryu SG et al. Treatment of relapsed acute lymphoblastic leukemia after allogeneic bone marrow transplantation with chemotherapy followed by G-CSF-primed donor leukocyte infusion: a prospective study. Bone Marrow Transplant 2005; 36: 163–169.

    CAS  PubMed  Google Scholar 

  27. Cardoso A, Schultze J, Boussiotis VA, Freeman GJ, Seamon MJ, Laszlo S et al. Pre-B acute lymphoblastic leukemia cells may induce T cell anergy to alloantigen. Blood 1996; 88: 41–48.

    CAS  PubMed  Google Scholar 

  28. Galandrini R, Albi N, Zarcone D, Grossi CE, Velardi A . Adhesion molecule-mediated signals regulate major histocompatibility complex-unrestricted and CD3/T cell receptor-triggered cytotoxicity. Eur J Immunol 1992; 22: 2047–2053.

    CAS  PubMed  Google Scholar 

  29. Han P, Story C, McDonald T, Mrozik K, Snell L . Immune escape mechanisms of childhood ALL and a potential countering role for DC-like leukemia cells. Cytotherapy 2002; 4: 165–175.

    CAS  PubMed  Google Scholar 

  30. Ruggeri L, Capanni M, Urbani E, Perruccio K, Shlomchik WD, Tosti A et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. [See comment]. Science 2002; 295: 2097–2100.

    CAS  PubMed  Google Scholar 

  31. Loren A, Luger S, Stadtmauer E, Tsai D, Schuster S, Nasta S et al. Intensive graft-versus-host disease prophylaxis is required after unrelated donor non-myeloablative stem cell transplantation. Bone Marrow Transplant 2005; 35: 921–926.

    CAS  PubMed  Google Scholar 

  32. Morris EC, Rebello P, Thomson KJ, Peggs KS, Kyriakou C, Goldstone AH et al. Pharmacokinetics of alemtuzumab used for in vivo and in vitro T-cell depletion in allogeneic transplantations: relevance for early adoptive immunotherapy and infectious complications. Blood 2003; 102: 404–406.

    CAS  PubMed  Google Scholar 

  33. Spitzer T, McAfee S, Sackstein R, Colby C, Toh H, Multani P 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.

    CAS  PubMed  Google Scholar 

  34. Peggs KS, Thomson K, Hart DP, Geary J, Morris EC, Yong K et al. Dose-escalated donor lymphocyte infusions following reduced intensity transplantation: toxicity, chimerism, and disease responses. [See comment]. Blood 2004; 103: 1548–1556.

    CAS  PubMed  Google Scholar 

  35. Tauro S, Craddock C, Peggs K, Begum G, Mahendra P, Cook G et al. Allogeneic stem-cell transplantation using a reduced-intensity conditioning regimen has the capacity to produce durable remissions and long-term disease-free survival in patients with high-risk acute myeloid leukemia and myelodysplasia. J Clin Oncol 2005; 23: 9387–9393.

    CAS  PubMed  Google Scholar 

  36. Schmid C, Schleuning M, Ledderose G, Tischer J, Kolb HJ . Sequential regimen of chemotherapy, reduced-intensity conditioning for allogeneic stem-cell transplantation, and prophylactic donor lymphocyte transfusion in high-risk acute myeloid leukemia and myelodysplastic syndrome. J Clin Oncol 2005; 23: 5675–5687.

    PubMed  Google Scholar 

  37. de Lima M, Bonamino M, Vasconcelos Z, Colares M, Diamond H, Zalcberg I et al. Prophylactic donor lymphocyte infusions after moderately ablative chemotherapy and stem cell transplantation for hematological malignancies: high remission rate among poor prognosis patients at the expense of graft-versus-host disease. Bone Marrow Transplant 2001; 27: 73–78.

    CAS  PubMed  Google Scholar 

  38. Antin JH, Childs R, Filipovich AH, Giralt S, Mackinnon S, Spitzer T et al. Establishment of complete and mixed donor chimerism after allogeneic lymphohematopoietic transplantation: recommendations from a workshop at the 2001 Tandem meetings of the international bone marrow transplant registry and the American society of blood and marrow transplantation. Biol Blood Marrow Transplant 2001; 7: 473–485.

    CAS  PubMed  Google Scholar 

  39. Antin J . Stem cell transplantation-harnessing of graft-vs-malignancy. Curr Opin Hematol 2003; 10: 440–444.

    PubMed  Google Scholar 

  40. Marks DI, Lush R, Cavenagh J, Milligan DW, Schey S, Parker A et al. The toxicity and efficacy of donor lymphocyte infusions given after reduced-intensity conditioning allogeneic stem cell transplantation. Blood 2002; 100: 3108–3114.

    CAS  PubMed  Google Scholar 

  41. Bethge WA, Hegenbart U, Stuart MJ, Storer BE, Maris MB, Flowers ME et al. Adoptive immunotherapy with donor lymphocyte infusions after allogeneic hematopoietic cell transplantation following nonmyeloablative conditioning. [See comment]. Blood 2004; 103: 790–795.

    CAS  PubMed  Google Scholar 

  42. Dey BR, McAfee S, Colby C, Sackstein R, Saidman S, Tarbell N et al. Impact of prophylactic donor leukocyte infusions on mixed chimerism, graft-versus-host disease, and antitumor response in patients with advanced hematologic malignancies treated with nonmyeloablative conditioning and allogeneic bone marrow transplantation. Biol Blood Marrow Transplant 2003; 9: 320–329.

    PubMed  Google Scholar 

  43. Loren A, Porter D . Donor leukocyte infusions after unrelated donor hematopoietic stem cell transplantation. Curr Opin Oncol 2006; 18: 107–114.

    PubMed  Google Scholar 

  44. Flowers M, Leisenring W, Beach K, Riddell S, Radich J, Higano C et al. Granulocyte colony-stimulating factor given to donors before apheresis does not prevent aplasia in patients treated with donor leukocyte infusion for recurrent chronic myeloid leukemia after bone marrow transplantation. Biol Blood Marrow Transplant 2000; 6: 321–326.

    CAS  PubMed  Google Scholar 

  45. 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 

  46. Mehta J, Powles R, Treleaven J, Horton C, Meller S, Pinkerton C et al. Outcome of acute leukemia relapsing after bone marrow transplantation: utility of second transplants and adoptive immunotherapy. Bone Marrow Transplant 1997; 19: 709–719.

    CAS  PubMed  Google Scholar 

  47. van Rhee R, Savage D, Blackwell J, Orchard K, Dazzi F, Lin F et al. Adoptive immunotherapy for relapse of chronic myeloid leukemia after allogeneic bone marrow transplant: equal efficacy of lymphocytes from sibling and matched unrelated donors. Bone Marrow Transplant 1998; 21: 1055–1061.

    CAS  PubMed  Google Scholar 

  48. 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 

  49. Porter D, Antin J . Adoptive immunotherapy in bone marrow transplantation. In: Burakoff S, Deeg H, Ferrara J (eds). Graft-versus-Host-Disease. Marcel Dekker: New York, 1997, pp 733–754.

    Google Scholar 

  50. 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 

  51. Korbling M, Giralt S, Khouri I, Mirza N, Donato M, Anderlini P et al. Donor lymphocyte apheresis for adoptive immunotherapy compared with blood stem cell apheresis. J Clin Apher 2001; 16: 82–87.

    CAS  PubMed  Google Scholar 

  52. 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 

  53. Soiffer R, Alyea E, Hochberg E, Wu C, Canning C, Parikh B 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.

    PubMed  Google Scholar 

  54. SCTC Group. Allogeneic peripheral blood stem-cell compared with bone marrow transplantation in the management of hematologic malignancies: an individual patient data meta-analysis of nine randomized trials. J Clin Oncol 2005; 23: 5074–5087.

    Google Scholar 

  55. Schmitz N, Barrett J . Optimizing engraftment—source and dose of stem cells. Semin Hematol 2002; 39: 3–14.

    PubMed  Google Scholar 

  56. Bensinger WI, Deeg HJ . Blood or marrow? Lancet 2000; 355: 1199–1200.

    CAS  PubMed  Google Scholar 

  57. Morris ES, MacDonald KP, Hill GR . Stem cell mobilization with G-CSF analogs: a rational approach to separate GVHD and GVL? Blood 2006; 107: 3430–3435.

    CAS  PubMed  Google Scholar 

  58. MacDonald KP, Rowe V, Filippich C, Johnson D, Morris ES, Clouston AD et al. Chronic graft-versus-host disease after granulocyte colony-stimulating factor-mobilized allogeneic stem cell transplantation: the role of donor T-cell dose and differentiation. Biol Blood Marrow Transplant 2004; 10: 373–385.

    CAS  PubMed  Google Scholar 

  59. Shiobara S, Nakao S, Ueda M, Yamazaki H, Takahashi S, Asano S et al. Donor leukocyte infusion for Japanese patients with relapsed leukemia after allogeneic bone marrow transplantation: indications and dose escalation. Ther Apher 2001; 5: 40–45.

    CAS  PubMed  Google Scholar 

  60. Porter D, Antin J . Graft-versus-leukemia effect of allogeneic bone marrow transplantation and donor mononuclear cell infusions. In: Winter J (ed). Blood Stem Cell Transplantation. Kluwer Academic Publishers: Norwell, MA, 1997, pp 57–86.

    Google Scholar 

  61. Akpek G, Boitnott JK, Lee LA, Hallick JP, Torbenson M, Jacobsohn DA et al. Hepatitic variant of graft-versus-host disease after donor lymphocyte infusion. Blood 2002; 100: 3903–3907.

    CAS  PubMed  Google Scholar 

  62. Marks DI, Lush R, Cavenagh J, Milligan DW, Schey S, Parker A et al. The toxicity and efficacy of donor lymphocyte infusions given after reduced-intensity conditioning allogeneic stem cell transplantation. Blood 2002; 100: 3108–3114.

    CAS  PubMed  Google Scholar 

  63. Alessandrino EP, Bernasconi P, Caldera D, Colombo A, Malcovati L, Martinelli G et al. Chemotherapy and donor peripheral blood progenitor cells for acute leukemia in early relapse after allogeneic bone marrow transplantation. Bone Marrow Transplant 1999; 23: 607–612.

    CAS  PubMed  Google Scholar 

  64. Siegert W, Beyer J, Kingreen D, Blasczyk R, Baurmann H, Schwella N et al. Treatment of relapse after allogeneic bone marrow transplantation with unmanipulated G-CSF-mobilized peripheral blood stem cell preparation. Bone Marrow Transplant 1998; 22: 579–583.

    CAS  PubMed  Google Scholar 

  65. Keil F, Haas OA, Fritsch G, Kalhs P, Lechner K, Mannhalter C 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 

  66. Liebowitz D, Lee K, CH J . Costimulatory approaches to adoptive immunotherapy. Curr Opin Oncol 1998; 10: 533–541.

    CAS  PubMed  Google Scholar 

  67. Laport GG, Levine BL, Stadtmauer EA, Schuster SJ, Luger SM, Grupp S et al. Adoptive transfer of costimulated T cells induces lymphocytosis in patients with relapsed/refractory non-Hodgkin lymphoma following CD34+-selected hematopoietic cell transplantation. Blood 2003; 102: 2004–2013.

    CAS  PubMed  Google Scholar 

  68. Rapoport A, Stadtmauer E, Aqui N, Badros A, Cotte J, Chrisley L et al. Restoration of immunity in lymphopenic individuals with cancer by vaccination and adoptive T-cell transfer. Nat Med 2005; 11: 1230–1237.

    CAS  PubMed  Google Scholar 

  69. Porter DL, Levine BL, Bunin N, Stadtmauer EA, Luger SM, Goldstein S et al. A phase I trial of donor lymphocyte infusions expanded and activated ex vivo via CD3/CD28 co-stimulation. Blood 2006; 107: 1325–1331.

    CAS  PubMed  Google Scholar 

  70. Cardoso AA, Seamon MJ, Afonso HM, Ghia P, Boussiotis VA, Freeman GJ et al. Ex vivo generation of human anti-pre-B leukemia-specific autologous cytolytic T cells. Blood 1997; 90: 549–561.

    CAS  PubMed  Google Scholar 

  71. Kolb HJ, Schmid C, Barrett AJ, Schendel DJ . Graft-versus-leukemia reactions in allogeneic chimeras. Blood 2004; 103: 767–776.

    CAS  PubMed  Google Scholar 

  72. Miklos DB, Kim HT, Zorn E, Hochberg EP, Guo L, Mattes-Ritz A et al. Antibody response to DBY minor histocompatibility antigen is induced after allogeneic stem cell transplantation and in healthy female donors. Blood 2004; 103: 353–359.

    CAS  PubMed  Google Scholar 

  73. Zorn E, Miklos DB, Floyd BH, Mattes-Ritz A, Guo L, Soiffer RJ et al. Minor histocompatibility antigen DBY elicits a coordinated B and T cell response after allogeneic stem cell transplantation. J Exp Med 2004; 199: 1133–1142.

    CAS  PubMed  PubMed Central  Google Scholar 

  74. 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 

  75. Clark RE, Dodi IA, Hill SC, Lill JR, Aubert G, Macintyre AR et al. Direct evidence that leukemic cells present HLA-associated immunogenic peptides derived from the BCR-ABL b3a2 fusion protein. Blood 2001; 98: 2887–2893.

    CAS  PubMed  Google Scholar 

  76. Voogt PJ, Goulmy E, Veenhof WF, Hamilton M, Fibbe WE, Van Rood JJ et al. Cellularly defined minor histocompatibility antigens are differentially expressed on human hematopoietic progenitor cells. J Exp Med 1988; 168: 2337–2347.

    CAS  PubMed  Google Scholar 

  77. 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 

  78. Marijt WA, Heemskerk MH, Kloosterboer FM, Goulmy E, Kester MG, van der Hoorn MA et al. Hematopoiesis-restricted minor histocompatibility antigens HA-1- or HA-2-specific T cells can induce complete remissions of relapsed leukemia. Proc Natl Acad Sci USA 2003; 100: 2742–2747.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Randolph SS, Gooley TA, Warren EH, Appelbaum FR, Riddell SR . Female donors contribute to a selective graft-versus-leukemia effect in male recipients of HLA-matched, related hematopoietic stem cell transplants. Blood 2004; 103: 347–352.

    CAS  PubMed  Google Scholar 

  80. Molldrem J, Dermime S, Parker K, Jiang YZ, Mavroudis D, Hensel N et al. Targeted T-cell therapy for human leukemia: cytotoxic T lymphocytes specific for a peptide derived from proteinase 3 preferentially lyse human myeloid leukemia cells. Blood 1996; 88: 2450–2457.

    CAS  PubMed  Google Scholar 

  81. 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.

    CAS  PubMed  Google Scholar 

  82. Heslop HE, Stevenson FK, Molldrem JJ . Immunotherapy of hematologic malignancy. Hematology Am Soc Hematol Educ Program 2003, 331–349.

    Google Scholar 

  83. Rosenfeld C, Cheever MA, Gaiger A . WT1 in acute leukemia, chronic myelogenous leukemia and myelodysplastic syndrome: therapeutic potential of WT1 targeted therapies. Leukemia 2003; 17: 1301–1312.

    CAS  PubMed  Google Scholar 

  84. Tamaki H, Ogawa H, Ohyashiki K, Ohyashiki JH, Iwama H, Inoue K et al. The Wilms' tumor gene WT1 is a good marker for diagnosis of disease progression of myelodysplastic syndromes. Leukemia 1999; 13: 393–399.

    CAS  PubMed  Google Scholar 

  85. Atanackovic D, Arfsten J, Cao Y, Gnjatic S, Schnieders F, Bartels K et al. Cancer-testis antigens are commonly expressed in multiple myeloma and induce systemic immunity following allogeneic stem cell transplantation. Blood 1103; 109: 1103–1112.

    Google Scholar 

  86. Greiner J, Schmitt M, Li L, Giannopoulos K, Bosch K, Schmitt A et al. Expression of tumor-associated antigens in acute myeloid leukemia: implications for specific immunotherapeutic approaches. Blood 2006; 108: 4109–4117.

    CAS  PubMed  Google Scholar 

  87. Falkenburg JH, Wafelman AR, Joosten P, Smit WM, van Bergen CA, Bongaerts R et al. Complete remission of accelerated phase chronic myeloid leukemia by treatment with leukemia-reactive cytotoxic T lymphocytes. Blood 1999; 94: 1201–1208.

    CAS  PubMed  Google Scholar 

  88. Montagna D, Maccario R, Montini E, Tonelli R, Lisini D, Pagani S et al. Generation and ex vivo expansion of cytotoxic T lymphocytes directed toward different types of leukemia or myelodysplastic cells using both HLA-matched and partially matched donors. Exp Hematol 2003; 31: 1031–1038.

    CAS  PubMed  Google Scholar 

  89. Dudley ME, Wunderlich JR, Shelton TE, Even J, Rosenberg SA . Generation of tumor-infiltrating lymphocyte cultures for use in adoptive transfer therapy for melanoma patients. J Immunother (1997) 2003; 26: 332–342.

    Google Scholar 

  90. Figlin RA, Pierce WC, Kaboo R, Tso CL, Moldawer N, Gitlitz B et al. Treatment of metastatic renal cell carcinoma with nephrectomy, interleukin-2 and cytokine-primed or CD8(+) selected tumor infiltrating lymphocytes from primary tumor. J Urol 1997; 158: 740–745.

    CAS  PubMed  Google Scholar 

  91. Servida P, Rossini S, Traversari C, Ferrari G, Bonini C, Nobili N et al. Gene transfer into peripheral blood lymphocytes for in vivo immunomodulation of donor anti-tumor immunity in a patient affected by EBV-induced lymphoma. Blood 1993; 82: 214a.

    Google Scholar 

  92. 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.

    CAS  PubMed  Google Scholar 

  93. Johnson BD, Becker EE, LaBelle JL, Truitt RL . Role of immunoregulatory donor T cells in suppression of graft-versus-host disease following donor leukocyte infusion therapy. J Immunol 1999; 163: 6479–6487.

    CAS  PubMed  Google Scholar 

  94. Johnson BD, Konkol MC, Truitt RL . CD25+ immunoregulatory T-cells of donor origin suppress alloreactivity after BMT. Biol Blood Marrow Transplant 2002; 8: 525–535.

    PubMed  Google Scholar 

  95. Trenado A, Sudres M, Tang Q, Maury S, Charlotte F, Gregoire S et al. Ex vivo-expanded CD4+CD25+ immunoregulatory T cells prevent graft-versus-host-disease by inhibiting activation/differentiation of pathogenic T cells. J Immunol 2006; 176: 1266–1273.

    CAS  PubMed  Google Scholar 

  96. Fowler DH, Odom J, Steinberg SM, Chow CK, Foley J, Kogan Y et al. Phase I clinical trial of costimulated, IL-4 polarized donor CD4+ T cells as augmentation of allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant 2006; 12: 1150–1160.

    CAS  PubMed  Google Scholar 

  97. Xia G, Truitt RL, Johnson BD . Graft-versus-leukemia and graft-versus-host reactions after donor lymphocyte infusion are initiated by host-type antigen-presenting cells and regulated by regulatory T cells in early and long-term chimeras. Biol Blood Marrow Transplant 2006; 12: 397–407.

    CAS  PubMed  Google Scholar 

  98. Mapara MY, Kim YM, Wang SP, Bronson R, Sachs DH, Sykes M . 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.

    CAS  PubMed  Google Scholar 

  99. Matte CC, Liu J, Cormier J, Anderson BE, Athanasiadis I, Jain D et al. Donor APCs are required for maximal GVHD but not for GVL. Nat Med 2004; 10: 987–992.

    CAS  PubMed  Google Scholar 

  100. Shlomchik W, Couzens M, Tang C, McNiff J, Robert M, Liu J et al. Prevention of graft-versus-host disease by inactivation of host antigen-presenting cells. Science 1999; 285: 412–415.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported in part by grants from The Leukemia & Lymphoma Society (7000-02) and NIH (K24 CA11787901) (DLP).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A W Loren.

Additional information

Conflict of interest

The authors have no conflicts of interest to declare.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Loren, A., Porter, D. Donor leukocyte infusions for the treatment of relapsed acute leukemia after allogeneic stem cell transplantation. Bone Marrow Transplant 41, 483–493 (2008). https://doi.org/10.1038/sj.bmt.1705898

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1705898

Keywords

Search

Quick links