Stem Cell Transplantation: Graft-Mediated Antileukemia Effects

Hogan, William J.; Deeg, Hans Joachim

doi:10.1385/1-59259-862-5:421

William J. Hogan³ &
Hans Joachim Deeg³

Part of the book series: Methods in Molecular Medicine™ ((MIMM,volume 109))

946 Accesses

Abstract

Graft-mediated antileukemia (GVL) activity is a major factor contributing to the success of allogeneic hematopoietic stem transplantation (aHCT). Recent advances have permitted the establishment of GVL activity without the need for a myeloablative conditioning regimen, thereby permitting even older and sicker patients to avail of potentially curative therapy. Use of adoptive immunotherapy by combining reduced intensity conditioning and donor leukocyte infusion (DLI) has resulted in strategies that can be exploited to maximize GVL effects while minimizing toxicity. These advances, combined with new molecularly targeted agents, creates new possibilities to develop less toxic, curative therapy for a greater number of patients. This review summarizes pertinent information regarding the evidence in favor of GVL effects, the impact of disease type and mechanisms of GVL.

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References

Porter D. L. and Antin, J. H. (1999) The graft-versus-leukemia effects of allogeneic cell therapy. [Review]. Annu. Rev. Med. 50, 369–386.
PubMed CAS Google Scholar
Clift, R. A., Buckner, C. D., Appelbaum, F. R., et al. (1990) Allogeneic marrow transplantation in patients with acute myeloid leukemia in first remission: a randomized trial of two irradiation regimens. Blood 76, 1867–1871.
PubMed CAS Google Scholar
Deeg, H. J., Storer, B., Slattery, J. T., et al. (2002) Conditioning with targeted busulfan and cyclophosphamide for hemopoietic stem cell transplantation from related and unrelated donors in patients with myelodysplastic syndrome. Blood 100, 1201–1207.
PubMed CAS Google Scholar
McSweeney, P. A., Niederwieser, D., Shizuru, J. A., et al. (2001) Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood 97, 3390–3400.
PubMed CAS Google Scholar
Slavin, S., Nagler, A., Naparstek, E., et al. (1998) Nonmyeloablative stem cell transplantation rand cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases. Blood 91, 756–763.
PubMed CAS Google Scholar
Giralt, S., Estey, E., Albitar, M., et al. (1997) Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. Blood 89, 4531–4536.
PubMed CAS Google Scholar
Mielcarek, M., Martin, P. J., Leisenring, W., et al. (2003) Graft-versus-host disease after nonmyeloablative versus conventional hematopoietic stem cell transplantation. Available online at First Edition Paper link, see Website: http://www.bloodjournal.org/. Blood 102(2), 756–762.
PubMed CAS Google Scholar
Weiden, P. L., Storb, R., Tsoi, M. S., Graham, T. C., Lerner, K. G., and Thomas, E. D. (1976) Infusion of donor lymphocytes into stable canine radiation chimeras: implications for mechanism of transplantation tolerance. J. Immunol. 116, 1212–1219.
PubMed CAS Google Scholar
Weiden, P. L., Sullivan, K. M., Flournoy, N., Storb, R., and Thomas, E. D. (1981) Antileukemic effect of chronic graft-versus-host disease: contribution to improved survival after allogeneic marrow transplantation. New Engl. J. Med. 304, 1529–1533.
PubMed CAS Google Scholar
Weiden, P. L., Flournoy, N., Thomas, E. D., et al. (1979) Antileukemic effect of graftversus-host disease in human recipients of allogeneic-marrow grafts. New Engl. J. Med. 300, 1068–1073.
PubMed CAS Google Scholar
Sullivan, K. M., Weiden, P. L., Storb, R., et al. (1989) 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 leukemia. Blood 73, 17201728.
Google Scholar
Odom, L. F., August, C. S., Githens, J. H., et al. (1978) Remission of relapsed leukaemia during a graft-versus-host reaction. A &quote;graft-versus-leukaemia reaction&quote; in man? Lancet 2, 537–540.
CAS Google Scholar
Collins, R. H., Jr., Rogers, Z. R., Bennett, M., Kumar, V., Nikein, A., and Fay, J. W. (1992) Hematologic relapse of chronic myelogenous leukemia following allogeneic bone marrow transplantation: apparent graft-versus-leukemia effect following abrupt discontinuation of immunosuppression. Bone Marrow Transplant. 10, 391–395.
PubMed Google Scholar
Higano, C. S., Brixey, M., Bryant, E. M., et al. (1990) Durable complete remission of acute nonlymphocytic leukemia associated with discontinuation of immunosuppression following relapse after allogeneic bone marrow transplantation. A case report of a probable graft-versus-leukemia effect. Transplantation 50, 175–177.
CAS Google Scholar
Fefer, A., Sullivan, K. M., Weiden, P., et al. (1987) Graft versus leukemia effect in man: the relapse rate of acute leukemia is lower after allogeneic than after syngeneic marrow transplantation. Prog. Clin. Biol. Res. 244, 401–408.
PubMed CAS Google Scholar
Gale, R. P., Horowitz, M. M., Ash, R. C., et al. (1994) Identical-twin bone marrow transplants for leukemia. Ann. Intern. Med. 120, 646–652.
PubMed CAS Google Scholar
Horowitz, M. M., Gale, R. P., Sondel, P. M., et al. (1990) Graft-versus-leukemia reactions after bone marrow transplantation. Blood 75, 555–562.
PubMed CAS Google Scholar
Apperley, J. F., Mauro, F. R., Goldman, J. M., et al. (1988) Bone marrow transplantation for chronic myeloid leukaemia in first chronic phase: importance of a graft-versus-leukaemia effect.[erratum; Br. J. Haematol. 70(2), 261]. Br. J. Haematol. 69, 239–245.
Google Scholar
Marmont, A. M., Horowitz, M. M., Gale, R. P., et al. (1991) T-cell depletion of HLA-identical transplants in leukemia. Blood 78, 2120–2130.
PubMed CAS Google Scholar
Kolb, H. J., Mittermuller, J., Clemm, C., et al. (1990) Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Blood 76, 2462–2465.
PubMed CAS Google Scholar
Barnes, D. W. H., Corp, M. J., Loutit, J. F., and Neal, F. E. (1956) Treatment of murine leukaemia with X-rays and homologous bone marrow. Preliminary communication. Br. Med. J. 2, 626–627.
PubMed CAS Google Scholar
Kolb, H. J., Schattenberg, A., Goldman, J. M., et al. (1995) Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. European Group for Blood and Marrow Transplantation Working Party Chronic Leukemia. Blood 86, 2041–2050.
PubMed CAS Google Scholar
Guglielmi, C., Arcese, W., Dazzi, F., et al. (2002) Donor lymphocyte infusion for relapsed chronic myelogenous leukemia: prognostic relevance of the initial cell dose. Blood 100, 397–405.
PubMed CAS Google Scholar
Raiola, A. M., Van Lint, M. T., Valbonesi, M., et al. (2003) Factors predicting response and graft-versus-host disease after donor lymphocyte infusions: a study on 593 infusions. Bone Marrow Transplant. 31, 687–693.
PubMed CAS Google Scholar
Shiobara, S., Nakao, S., Ueda, M., et al. (2001) Donor leukocyte infusion for Japanese patients with relapsed leukemia after allogeneic bone marrow transplantation: indications and dose escalation. Ther. Apheresis 5, 40–45.
CAS Google Scholar
Collins, R. H., Jr., Shpilberg, O., Drobyski, W. R., et al. (1997) Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation. J. Clin. Oncol. 15, 433–444.
PubMed Google Scholar
Marks, D. I., Lush, R., Cavenagh, J., et al. (2002) The toxicity and efficacy of donor lymphocyte infusions given after reduced-intensity conditioning allogeneic stem cell transplantation. Blood 100, 3108–3114.
PubMed CAS Google Scholar
de Lima, M., Bonamino, M., Vasconcelos, Z., et al. (2001) 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. 27, 73–78.
PubMed Google Scholar
Porter, D. L., Collins, R. H., Jr., Hardy, C., et al. (2000) Treatment of relapsed leukemia after unrelated donor marrow transplantation with unrelated donor leukocyte infusions. Blood 95, 1214–1221.
PubMed CAS Google Scholar
Lokhorst, H. M., Schattenberg, A., Cornelissen, J. J., et al. (2000) Donor lymphocyte infusions for relapsed multiple myeloma after allogeneic stem-cell transplantation: predictive factors for response and long-term outcome. J. Clin. Oncol. 18, 3031–3037.
PubMed CAS Google Scholar
Dazzi, F., Szydlo, R. M., Craddock, C., et al. (2000) Comparison of single-dose and escalating-dose regimens of donor lymphocyte infusion for relapse after allografting for chronic myeloid leukemia. Blood 95, 67–71.
PubMed CAS Google Scholar
Dazzi, F., Szydlo, R. M., Cross, N. C., et al. (2000) Durability of responses following donor lymphocyte infusions for patients who relapse after allogeneic stem cell transplantation for chronic myeloid leukemia. Blood 96, 2712–2716.
PubMed CAS Google Scholar
Or, R., Shapira, M. Y., Resnick, I., et al. (2003) Nonmyeloablative allogeneic stem cell transplantation for the treatment of chronic myeloid leukemia in first chronic phase. Blood 101, 441–445.
PubMed CAS Google Scholar
Au, W. Y., Lie, A. K., Lee, C. K., Liang, R., and Kwong, Y. L.. (1999) Donor lymphocyte infusion induced molecular remission in relapse of acute myeloid leukaemia after allogeneic bone marrow transplantation. Bone Marrow Transplant. 23, 1201–1203.
PubMed CAS Google Scholar
Lee, J. H., Lee, K. H., Kim, S., et al. (2001) Combination chemotherapy of intermediate-dose cytarabine, idarubicin, plus etoposide and subsequent mobilized donor leukocyte infusion for relapsed acute leukemia after allogeneic bone marrow transplantation. Leukemia Res. 25, 305–312.
CAS Google Scholar
Zikos, P., Van Lint, M. T., Lamparelli, T., et al. (1998) 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 83, 896–903.
PubMed CAS Google Scholar
Appelbaum, F. R. (1997) Graft versus leukemia (GVL) in the therapy of acute lymphoblastic leukemia (ALL). [Review] Leukemia 11(Suppl 4), S15–17.
PubMed Google Scholar
Passweg, J. R., Tiberghien, P., Cahn, J. Y., et al. (1998) Graft-versus-leukemia effects in T lineage and B lineage acute lymphoblastic leukemia. Bone Marrow Transplant. 21, 153-158.
Google Scholar
Collins, R. H., Jr., Goldstein, S., Giralt, S., et al. (2000) Donor leukocyte infusions in acute lymphocytic leukemia. Bone Marrow Transplant. 26, 511–516.
PubMed Google Scholar
Zomas, A., Stefanoudaki, K., Fisfis, M., Papadaki, T., and Mehta, J.. (1998) Graft-versus-myeloma after donor leukocyte infusion: maintenance of marrow remission but extramed-ullary relapse with plasmacytomas. Bone Marrow Transplant. 21, 1163–1165.
PubMed CAS Google Scholar
Tricot, G, Vesole, DH, Jagannath, S, Hilton, J, Munshi, N, and Barlogie, B. (1996) Graft-versus-myeloma effect: proof of principle. Blood 87, 1196–1198.
PubMed CAS Google Scholar
Alyea, E., Weller, E., Schlossman, R., et al. (2001) T-cell-depleted allogeneic bone marrow transplantation followed by donor lymphocyte infusion in patients with multiple myeloma: induction of graft-versus-myeloma effect. Blood 98, 934–939.
PubMed CAS Google Scholar
Verdonck, L. F., Lokhorst, H. M., Dekker, A. W., Nieuwenhuis, H. K., and Petersen, E. J. (1996) Graft-versus-myeloma effect in two cases. Lancet 347, 800–801.
PubMed CAS Google Scholar
Bertz, H., Burger, J. A., Kunzmann, R., Mertelsmann, R., and Finke, J. (1997) Adoptive immunotherapy for relapsed multiple myeloma after allogeneic bone marrow transplantation (BMT): evidence for a graft-versus-myeloma effect. Leukemia 11, 281–283.
PubMed CAS Google Scholar
Mehta, J., Powles, R., Singhal, S., Iveson, T., Treleaven, J., and Catovsky, D. (1996) Clinical and hematologic response of chronic lymphocytic and prolymphocytic leukemia persisting after allogeneic bone marrow transplantation with the onset of acute graft-versus-host disease: possible role of graft-versus-leukemia. Bone Marrow Transplant. 17, 371–375.
PubMed CAS Google Scholar
Rondon, G., Giralt, S., Huh, Y., et al. (1996) Graft-versus-leukemia effect after allogeneic bone marrow transplantation for chronic lymphocytic leukemia. Bone Marrow Transplant. 18, 669–672.
PubMed CAS Google Scholar
Dreger, P. and Montserrat, E. (2002) Autologous and allogeneic stem cell transplantation for chronic lymphocytic leukemia. [Review]. Leukemia 16, 985–992.
PubMed CAS Google Scholar
Sohn, S. K., Baek, J. H., Kim, D. H., et al. (2000) Successful allogeneic stem-cell transplantation with prophylactic stepwise G-CSF primed-DLIs for relapse after autologous transplantation in mantle cell lymphoma: a case report and literature review on the evidence of GVL effects in MCL. [Review]. Am. J. Hematol. 65, 75–80.
PubMed CAS Google Scholar
Khouri, I. F., Keating, M., Korbling, M., et al. (1998) Transplant-lite: induction of graftversus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment for lymphoid malignancies. J. Clin. Oncol. 16, 2817–2824.
PubMed CAS Google Scholar
Khouri, I. F., Saliba, R. M., Giralt, S. A., et al. (2001) Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality. Blood 98, 3595–3599.
PubMed CAS Google Scholar
Branson, K., Chopra, R., Kottaridis, P. D., et al. (2002) Role of nonmyeloablative allogeneic stem-cell transplantation after failure of autologous transplantation in patients with lymphoproliferative malignancies. J. Clin. Oncol. 20, 4022–4031.
PubMed Google Scholar
Milpied, N., Fielding, A. K., Pearce, R. M., Ernst, P., and Goldstone, A. H. (1996) Allogeneic bone marrow transplant is not better than autologous transplant for patients with relapsed Hodgkin’s disease. European Group for Blood and Bone Marrow Transplantation. J. Clin. Oncol. 14, 1291–1296.
PubMed CAS Google Scholar
Akpek, G., Ambinder, R. F., Piantadosi, S., et al. (2001) Long-term results of blood and marrow transplantation for Hodgkin’s lymphoma. J. Clin. Oncol. 19, 4314–4321.
PubMed CAS Google Scholar
Carella, A. M., Cavaliere, M., Lerma, E., et al. (2000) Autografting followed by nonmyeloablative immunosuppressive chemotherapy and allogeneic peripheral-blood hematopoietic stem-cell transplantation as treatment of resistant Hodgkin’s disease and non-Hodgkin’s lymphoma. J. Clin. Oncol. 18, 3918–3924.
PubMed CAS Google Scholar
Porter, D. L., Stadtmauer, E. A., and Lazarus, H. M. (2003)’ GVHD’: graft-versus-host disease or graft-versus-Hodgkin’s disease? an old acronym with new meaning. Bone Marrow Transplant. 31, 739–746.
PubMed CAS Google Scholar
Eibl, B., Schwaighofer, H., Nachbaur, D., et al. (1996) Evidence for a graft-versus-tumor effect in a patient treated with marrow ablative chemotherapy and allogeneic bone marrow transplantation for breast cancer. Blood 88, 1501–1508.
PubMed CAS Google Scholar
Childs, R., Chernoff, A., Contentin, N., et al. (2000) Regression of metastatic renal-cell carcinoma after nonmyeloablative allogeneic peripheral-blood stem-cell transplantation. New Engl. J. Med. 343, 750–758.
PubMed CAS Google Scholar
Rini, B. I., Zimmerman, T., Stadler, W. M., Gajewski, T. F., and Vogelzang, N. J. (2002) Allogeneic stem-cell transplantation of renal cell cancer after nonmyeloablative chemotherapy: feasibility, engraftment, and clinical results.[comment]. J. Clin. Oncol. 20, 2017–2024.
PubMed Google Scholar
Bregni, M., Dodero, A., Peccatori, J., et al. (2002) Nonmyeloablative conditioning followed by hematopoietic cell allografting and donor lymphocyte infusions for patients with metastatic renal and breast cancer. Blood 99, 4234–4236.
PubMed CAS Google Scholar
Bay, J. O., Fleury, J., Choufi, B., et al. (2002) Allogeneic hematopoietic stem cell transplantation in ovarian carcinoma: results of five patients. Bone Marrow Transplant. 30, 95–102.
PubMed Google Scholar
Peccatori, J. Ciceri, F., Bernardi, M., et al. (2002) Evidence of allogeneic graft-versustumor effect in prostate and ovarian cancer. Haematologica 87(Suppl1), 12–14.
Google Scholar
Zetterquist, H., Hentschke, P., Thorne, A., et al. (2001) A graft-versus-colonic cancer effect of allogeneic stem cell transplantation. Bone Marrow Transplant. 28, 1161–1166.
PubMed CAS Google Scholar
Moscardo, F., Martinez, J. A., Sanz, G. F., et al. (2000) Graft-versus-tumour effect in nonsmall-cell lung cancer after allogeneic peripheral blood stem cell transplantation. Br. J. Haematol. 111, 708–710.
PubMed CAS Google Scholar
Pedrazzoli, P., Da Prada, G. A., Giorgiani, G., et al. (2002) Allogeneic blood stem cell transplantation after a reduced-intensity, preparative regimen: a pilot study in patients with refractory malignancies. Cancer 94, 2409–2415.
PubMed Google Scholar
Morecki, S., Moshel, Y., Gelfend, Y., Pugatsch, T., and Slavin, S. (1997) Induction of graft vs. tumor effect in a murine model of mammary adenocarcinoma. Int. J. Cancer 71, 59–63.
PubMed CAS Google Scholar
Morecki, S., Yacovlev, E., Diab, A., and Slavin, S. (1998) Allogeneic cell therapy for a murine mammary carcinoma. Cancer Research. 58, 3891–3895.
PubMed CAS Google Scholar
Childs, R. W., Bradstock, K. F., Gottlieb, D., Kefford, R., and Barrett, J. (2000) Nonmyeloablative allogeneic stem cell transplantation as immunotherapy for metastatic melanoma: results of a pilot study. Blood 96(Part2), 353b..
Google Scholar
Foster, A. E., Gottlieb, D. J., Marangolo, M., et al. (2003) Rapid, large-scale generation of highly pure cytomegalovirus-specific cytotoxic T cells for adoptive immunotherapy. J. Hematother. Stem Cell Res. 12, 93–105.
PubMed CAS Google Scholar
Walter, E. A., Greenberg, P. D., Gilbert, M. J., et al. (1995) Reconstitution of cellular immunity against cytomegalovirus in recipients of allogeneic bone marrow by transfer of T-cell clones from the donor. New Engl. J. Med. 333, 1038–1044.
PubMed CAS Google Scholar
Riddell, S. R., Watanabe, K. S., Goodrich, J. M., Li, C. R., Agha, M. E., and Greenberg, P. D. (1992) Restoration of viral immunity in immunodeficient humans by the adoptive transfer of T cell clones. Science 257, 238–241.
PubMed CAS Google Scholar
Gottschalk, S., Edwards, O. L., Sili, U., et al. (2003) Generating CTLs against the subdominant Epstein-Barr virus LMP1 antigen for the adoptive immunotherapy of EBVassociated malignancies. Blood 101, 1905–1912.
PubMed CAS Google Scholar
Hamel, Y., Blake, N., Gabrielsson, S., et al. (2002) Adenovirally transduced dendritic cells induce bispecific cytotoxic T lymphocyte responses against adenovirus and cytomegalovirus pp65 or against adenovirus and Epstein-Barr virus EBNA3C protein: a novel approach for immunotherapy. Hum. Gene Ther. 13, 855–866.
PubMed CAS Google Scholar
Regn, S., Raffegerst, S., Chen, X., Schendel, D., Kolb, H. J., and Roskrow, M.. (2001) Ex vivo generation of cytotoxic T lymphocytes specific for one or two distinct viruses for the prophylaxis of patients receiving an allogeneic bone marrow transplant. Bone Marrow Transplant. 27, 53–64.
PubMed CAS Google Scholar
Hromas, R., Cornetta, K., Srour, E., Blanke, C., and Broun, E. R. (1994) Donor leukocyte infusion as therapy of life-threatening adenoviral infections after T-cell-depleted bone marrow transplantation. Blood 84, 1689–1690.
PubMed CAS Google Scholar
Rooney, C. M., Smith, C. A., Ng, C. Y., et al. (1998) Infusion of cytotoxic T cells for the prevention and treatment of Epstein-Barr virus-induced lymphoma in allogeneic transplant recipients. Blood 92, 1549–1555.
PubMed CAS Google Scholar
Emanuel, D. J., Lucas, K. G., Mallory, G. B., Jr., et al. (1997) Treatment of posttransplant lymphoproliferative disease in the central nervous system of a lung transplant recipient using allogeneic leukocytes. Transplantation 63, 1691–1694.
PubMed CAS Google Scholar
Comoli, P., Labirio, M., Basso, S., et al. (2002) Infusion of autologous Epstein-Barr virus (EBV)-specific cytotoxic T cells for prevention of EBV-related lymphoproliferative disorder in solid organ transplant recipients with evidence of active virus replication. Blood 99, 2592–2598.
PubMed CAS Google Scholar
Haque, T., Taylor, C., Wilkie, G. M., et al. (2001) Complete regression of posttransplant lymphoproliferative disease using partially HLA-matched Epstein Barr virus-specific cytotoxic T cells. Transplantation 72, 1399–1402.
PubMed CAS Google Scholar
Restrepo, A., Albrecht, F., Raez, L. E., et al. (1999) Post-liver transplantation lymphoproliferative disorders with and without infusions of donor bone marrow cells. [Review] Crit. Rev. Oncogen. B, 239–245.
Google Scholar
Truitt, R. L., Johnson, B. D., McCabe, C., and Weiler, M. B. (1997) Graft versus leukemia. In: Graft-vs-Host Disease. Ferrara, J. L. M, Deeg, H. J., and Burakoff, S. J., eds. Marcel Dekker, New York, NY, p. 385.
Google Scholar
Malkovska, V., Cigel, F., and Storer, B. E. (1994) Human T cells in hu-PBL-SCID mice proliferate in response to Daudi lymphoma and confer anti-tumour immunity. Clin. Exp. Immunol. 96, 158–165.
PubMed CAS Google Scholar
van Lochem, E., de Gast, B., and Goulmy, E. (1992) In vitro separation of host specific graft-versus-host and graft-versus-leukemia cytotoxic T cell activities. Bone Marrow Transplant. 10, 181–183.
PubMed Google Scholar
Sosman, J. A., Oettel, K. R., Smith, S. D., Hank, J. A., Fisch, P., and Sondel, P. M. (1990) Specific recognition of human leukemic cells by allogeneic T cells: II. Evidence for HLAD restricted determinants on leukemic cells that are crossreactive with determinants present on unrelated nonleukemic cells. Blood 75, 2005–2016.
PubMed CAS Google Scholar
Kondo, Y., Shiobara, S., and Nakao, S. (2001) Identification of T-cell clones showing expansion associated with graft-vs-leukemia effect on chronic myelogenous leukemia in vivo and in vitro. Exp. Hematol. 29, 471–476.
PubMed CAS Google Scholar
Jiang, Y. Z., Kanfer, E. J., Macdonald, D., Cullis, J. O., Goldman, J. M., and Barrett, A. J. (1991) Graft-versus-leukaemia following allogeneic bone marrow transplantation: emergence of cytotoxic T lymphocytes reacting to host leukaemia cells. Bone Marrow Transplant. 8, 253–258.
PubMed CAS Google Scholar
Korngold, R., and Sprent, J. (1987) T cell subsets and graft-versus-host disease. Transplantation 44, 335–339.
PubMed CAS Google Scholar
Giralt, S., Hester, J., Huh, Y., et al. (1995) CD8-depleted donor lymphocyte infusion as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation. Blood 86, 4337–4343.
PubMed CAS Google Scholar
Nimer, S. D., Giorgi, J., Gajewski, J. L., et al. (1994) Selective depletion of CD8+cells for prevention of graft-versus-host disease after bone marrow transplantation. A randomized controlled trial. Transplantation 57, 82–87.
PubMed CAS Google Scholar
Alyea, E. P., Soiffer, R. J., Canning, C., et al. (1998) Toxicity and efficacy of defined doses of CD4(+) donor lymphocytes for treatment of relapse after allogeneic bone marrow transplant. Blood 91, 3671–3680.
PubMed CAS Google Scholar
Claret, E. J., Alyea, E. P., Orsini, E., et al. (1997) Characterization of T cell repertoire in patients with graft-versus-leukemia after donor lymphocyte infusion. J. Clin. Invest. 100, 855–866.
PubMed CAS Google Scholar
Faber, L. M., van Luxemburg-Heijs, S. A., Veenhof, W. F., Willemze, R., and Falkenburg, J. H. (1995) Generation of CD4+cytotoxic T-lymphocyte clones from a patient with severe graft-versus-host disease after allogeneic bone marrow transplantation: implications for graft-versus-leukemia reactivity. Blood 86, 2821–2828.
PubMed CAS Google Scholar
Jiang, Y. Z., and Barrett, A. J. (1995) Cellular and cytokine-mediated effects of CD4positive lymphocyte lines generated in vitro against chronic myelogenous leukemia. Exp. Hematol. 23, 1167–1172.
PubMed CAS Google Scholar
Truitt, R. L., and Johnson, B. D. (1995) Principles of graft-vs.-leukemiareactivity. [Review] Biol. Blood Marrow Transplant. 1, 61–68.
PubMed CAS Google Scholar
Palathumpat, V., Dejbakhsh-Jones, S., and Strober, S. (1995) The role of purified CD8+T cells in graft-versus-leukemia activity and engraftment after allogeneic bone marrow transplantation. Transplantation 60, 355–361.
PubMed CAS Google Scholar
Barrett, A. J. (1997) Mechanisms of the graft-versus-leukemia reaction. [Review] Stem Cells 15, 248–258.
PubMed CAS Google Scholar
Eisendle, K., Lang, A., Eibl, B., et al. (2003) Phenotypic and functional deficiencies of leukaemic dendritic cells from patients with chronic myeloid leukaemia. Br. J. Haematol. 120, 63–73.
PubMed Google Scholar
Eibl, B., Ebner, S., Duba, C., et al. (1997) Dendritic cells generated from blood precursors of chronic myelogenous leukemia patients carry the Philadelphia translocation and can induce a CML-specific primary cytotoxic T-cell response. Genes Chromosomes Cancer 20, 215–223.
PubMed CAS Google Scholar
Dietz, A. B., Litzow, M. R., Bulur, P. A., and Vuk-Pavlovic, S.(2001) Transgenic interleukin 2 secreted by CML dendritic cells stimulates autologous T(H)1 T cells. Cytotherapy 3, 97–105.
PubMed CAS Google Scholar
Trinchieri, G. (1989) Biology of natural killer cells. [Review] Adv. Immunol. 47, 187–376.
PubMed CAS Google Scholar
Hercend, T., Takvorian, T., Nowill, A., et al. (1986) Characterization of natural killer cells with antileukemia activity following allogeneic bone marrow transplantation. Blood 67, 722–728.
PubMed CAS Google Scholar
Kruit, W. H., Goey, S. H., Lamers, C. H., et al. (1997) High-dose regimen of interleukin2 and interferon-alpha in combination with lymphokine-activated killer cells in patients with metastatic renal cell cancer. J. Immunother. 20, 312–320.
PubMed CAS Google Scholar
Law, T. M., Motzer, R. J., Mazumdar, M., et al. (1995) Phase III randomized trial of interleukin-2 with or without lymphokine-activated killer cells in the treatment of patients with advanced renal cell carcinoma. Cancer 76, 824–832.
PubMed CAS Google Scholar
Okuno, K., Takagi, H., Nakamura, T., Nakamura, Y., Iwasa, Z., and Yasutomi, M. (1986) Treatment for unresectable hepatoma via selective hepatic arterial infusion of lymphokine-activated killer cells generated from autologous spleen cells. Cancer 58, 1001–1006.
Google Scholar
Kimura, H. and Yamaguchi, Y. (1995) Adjuvant immunotherapy with interleukin 2 and lymphokine-activated killer cells after noncurative resection of primary lung cancer. Lung Cancer 13, 31–44.
PubMed CAS Google Scholar
Lim, S. H., Newland, A. C., Kelsey, S., et al. (1992) Continuous intravenous infusion of high-dose recombinant interleukin-2 for acute myeloid leukaemia-a phase II study. Cancer Immunol. Immunother. 34, 337–342.
PubMed CAS Google Scholar
Meropol, N. J., Barresi, G. M., Fehniger, T. A., Hitt, J., Franklin, M., and Caligiuri, M. A. (1998) Evaluation of natural killer cell expansion and activation in vivo with daily subcutaneous low-dose interleukin-2 plus periodic intermediate-dose pulsing. Cancer Immunol. Immunother. 46, 318–326.
PubMed CAS Google Scholar
Farag, S. S., Fehniger, T. A., Ruggeri, L., Velardi, A., and Caligiuri, M. A. (2002) Natural killer cell receptors: new biology and insights into the graft-versus-leukemia effect. [Review] Blood 100, 1935–1947.
PubMed CAS Google Scholar
Ruggeri, L., Capanni, M., Casucci, M., et al. (1999) Role of natural killer cell alloreactivity in HLA-mismatched hematopoietic stem cell transplantation. Blood 94, 333–339.
PubMed CAS Google Scholar
Zeis, M., Uharek, L., Glass, B., et al. (1997) Allogeneic MHC-mismatched activated natural killer cells administered after bone marrow transplantation provide a strong graft-versus-leukaemia effect in mice. Br. J. Haematol. 96, 757–761.
PubMed CAS Google Scholar
Glass, B., Uharek, L., Zeis, M., Loeffler, H., Mueller-Ruchholtz, W., and Gassmann, W. (1996) Graft-versus-leukaemia activity can be predicted by natural cytotoxicity against leukaemia cells. Br. J. Haematol. 93, 412–420.
PubMed CAS Google Scholar
Ruggeri, L., Capanni, M., Martelli, M. F., and Velardi, A. (2001) Cellular therapy: exploiting NK cell alloreactivity in transplantation. [Review] Curr. Opin. Hematol. 8, 355–359.
PubMed CAS Google Scholar
Jiang, Y. Z., Barrett, A. J., Goldman, J. M., and Mavroudis, D. A. (1997) Association of natural killer cell immune recovery with a graft-versus-leukemia effect independent of graft-versus-host disease following allogeneic bone marrow transplantation. Ann. Hematol. 74, 1–6.
PubMed CAS Google Scholar
Jiang, Y. Z., Cullis, J. O., Kanfer, E. J., Goldman, J. M., and Barrett, A. J. (1993) T cell and NK cell mediated graft-versus-leukaemia reactivity following donor buffy coat transfusion to treat relapse after marrow transplantation for chronic myeloid leukaemia. Bone Marrow Transplant. 11, 133–138.
PubMed CAS Google Scholar
Aversa, F., Tabilio, A., Velardi, A., et al. (1998) Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype. New Engl. J. Med. 339, 1186–1193.
PubMed CAS Google Scholar
Ruggeri, L., Capanni, M., Urbani, E., et al. (2002) Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science 295, 2097–2100.
PubMed CAS Google Scholar
Falkenburg, J. H., Marijt, W. A., Heemskerk, M. H., and Willemze, R. (2002) Minor histocompatibility antigens as targets of graft-versus-leukemia reactions. Curr. Opin. Hematol. 9, 497–502.
PubMed CAS Google Scholar
Riddell, S. R., Murata, M., Bryant, S., and Warren, E. H. (2002) Minor histocompatibility antigens-targets of graft versus leukemia responses. Intl. J. Hematol. 2, 155–161.
Google Scholar
Goulmy, E. (1997) Human minor histocompatibility antigens: new concepts for marrow transplantation and adoptive immunotherapy. [Review] Immun. Revs. 157, 125–140.
CAS Google Scholar
Wang, W., Meadows, L. R., den Haan, J. M., et al. (1995) Human H-Y: a male-specific histocompatibility antigen derived from the SMCY protein. Science 269, 1588–1590.
PubMed CAS Google Scholar
Warren, E. H., Gavin, M. A., Simpson, E., et al. (2000) The human UTY gene encodes a novel HLA-B8-restricted H-Y antigen. J. Immunol. 164, 2807–2814.
PubMed CAS Google Scholar
Vogt, M. H., van den Muijsenberg, J. W., Goulmy, E., et al. (2002) The DBY gene codes for an HLA-DQ5-restricted human male-specific minor histocompatibility antigen involved in graft-versus-host disease. Blood 99, 3027–3032.
PubMed CAS Google Scholar
Vogt, M. H., Goulmy, E., Kloosterboer, F. M., et al. (2000) UTY gene codes for an HLAB60-restricted human male-specific minor histocompatibility antigen involved in stem cell graft rejection: characterization of the critical polymorphic amino acid residues for T-cell recognition. Blood 96, 3126–3132.
PubMed CAS Google Scholar
Vogt, M. H., de Paus, R. A., Voogt, P. J., Willemze, R., and Falkenburg, J. H. (2000) DFFRY codes for a new human male-specific minor transplantation antigen involved in bone marrow graft rejection. Blood 95, 1100–1105.
PubMed CAS Google Scholar
Brickner, A. G., Warren, E. H., Caldwell, J. A., et al. (2001) The immunogenicity of a new human minor histocompatibility antigen results from differential antigen processing. J. Exp. Med. 193, 195–206.
PubMed CAS Google Scholar
Pierce, R. A., Field, E. D., Mutis, T., et al. (2001) The HA-2 minor histocompatibility antigen is derived from a diallelic gene encoding a novel human class I myosin protein. J. Immunol. 167, 3223–3230.
PubMed CAS Google Scholar
de Bueger, M., Bakker, A., Van Rood, J. J., Van der Woude, F., and Goulmy, E. (1992) Tissue distribution of human minor histocompatibility antigens. Ubiquitous versus restricted tissue distribution indicates heterogeneity among human cytotoxic T lymphocytedefined non-MHC antigens. J. Immunol. 149, 1788–1794.
PubMed Google Scholar
Warren, E. H., Gavin, M., Greenberg, P. D., and Riddell, S. R. (1998) Minor histocompatibility antigens as targets for T-cell therapy after bone marrow transplantation. [Review] Curr. Opin. Hematol. 5, 429–433.
PubMed CAS Google Scholar
Pardoll, D. M. (2002) Spinning molecular immunology into successful immunotherapy. [Review] Nat. Rev. Immunol. 2, 227–238.
PubMed CAS Google Scholar
Clark, S. S., McLaughlin, J., Crist, W. M., Champlin, R., and Witte, O. N. (1987) Unique forms of the abl tyrosine kinase distinguish Ph1-positive CML from Ph1-positive ALL. Science 235, 85–88.
PubMed CAS Google Scholar
Kurzrock, R., Blick, M. B., Talpaz, M., et al. (1986) Rearrangement in the breakpoint cluster region and the clinical course in Philadelphia-negative chronic myelogenous leukemia. Ann. Intern. Med. 105, 673–679.
PubMed CAS Google Scholar
Ben-Neriah, Y., Daley, G. Q., Mes-Masson, A. M., Witte, O. N., and Baltimore, D. (1986) The chronic myelogenous leukemia-specific P210 protein is the product of the bcr/abl hybrid gene. Science 233, 212–214.
PubMed CAS Google Scholar
Heisterkamp, N., Stam, K., Groffen, J., de Klein, A., and Grosveld, G. (1985) Structural organization of the bcr gene and its role in the Ph’ translocation. Nature 315, 758761.
Google Scholar
Fossum, B., Gedde-Dahl, T., 3rd, Breivik, J., et al. (1994) p21-ras-peptide-specific T-cell responses in a patient with colorectal cancer. CD4+and CD8+T cells recognize a peptide corresponding to a common mutation (13Gly-≫Asp). Int. J. Cancer 56, 40–45.
PubMed CAS Google Scholar
Yotnda, P., Garcia, F., Peuchmaur, M., et al. (1998) Cytotoxic T cell response against the chimeric ETV6-AML1 protein in childhood acute lymphoblastic leukemia. J. Clin. Invest. 102, 455–462.
PubMed CAS Google Scholar
Ohminami, H., Yasukawa, M., Kaneko, S., et al. (1999) Fas-independent and nonapoptotic cytotoxicity mediated by a human CD4(+) T-cell clone directed against an acute myelogenous leukemia-associated DEK-CAN fusion peptide. Blood 93, 925–935.
PubMed CAS Google Scholar
Boer, J., Mahmoud, H., Raimondi, S., Grosveld, G., and Krance, R. (1997) Loss of the DEK-CAN fusion transcript in a child with t(6;9) acute myeloid leukemia following chemotherapy and allogeneic bone marrow transplantation. Leukemia 11, 299–300.
PubMed CAS Google Scholar
Fornerod, M., Boer, J., van Baal, S., Morreau, H., and Grosveld, G. (1996) Interaction of cellular proteins with the leukemia specific fusion proteins DEK-CAN and SET-CAN and their normal counterpart, the nucleoporin CAN. Oncogene 13, 1801–1808.
PubMed CAS Google Scholar
von Lindern, M., Fornerod, M., Soekarman, N., et al. (1992) Translocation t(6;9) in acute non-lymphocytic leukaemia results in the formation of a DEK-CAN fusion gene. [Review] [74 refs]. Baillieres Clin. Haematol. 5, 857–879.
Google Scholar
de The, H., Lavau, C., Marchio, A., Chomienne, C., Degos, L., and Dejean, A. (1991) The PML-RAR alpha fusion mRNA generated by the t(15;17) translocation in acute promyelocytic leukemia encodes a functionally altered RAR. Cell 66, 675–684.
PubMed Google Scholar
Kakizuka, A., Miller, W. H., Jr., Umesono, K., et al. (1991) Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RAR alpha with a novel putative transcription factor, PML. Cell 66, 663–674.
PubMed CAS Google Scholar
Molldrem, J. J., Lee, P. P., Wang, C., et al. (2000) Evidence that specific T lymphocytes may participate in the elimination of chronic myelogenous leukemia. Nat. Med. 6, 10181023.
Google Scholar
Molldrem, J. J., Clave, E., Jiang, Y. Z., et al. (1997) Cytotoxic T lymphocytes specific for a nonpolymorphic proteinase 3 peptide preferentially inhibit chronic myeloid leukemia colony-forming units. Blood 90, 2529–2534.
PubMed CAS Google Scholar
Molldrem, J., Dermime, S., Parker, K., et al. (1996) 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 88, 2450–2457.
PubMed CAS Google Scholar
Clave, E., Molldrem, J., Hensel, N., Raptis, A., and Barrett, A. J. (1999) Donor-recipient polymorphism of the proteinase 3 gene: a potential target for T-cell alloresponses to myeloid leukemia. J. Immunother. 22, 1–6.
PubMed CAS Google Scholar
Boon, T. and Old, L. J. (1997) Cancer tumor antigens. Curr. Opin. Immunol. 9, 681–683.
PubMed CAS Google Scholar
Robbins, P. F. and Kawakami, Y. (1996) Human tumor antigens recognized by T cells. [Review] Curr. Opin. Immunol. 8, 628–636.
PubMed CAS Google Scholar
Ohminami, H., Yasukawa, M., and Fujita, S. (2000) HLA class I-restricted lysis of leukemia cells by a CD8(+) cytotoxic T-lymphocyte clone specific for WT1 peptide. Blood 95, 286–293.
PubMed CAS Google Scholar
Oka, Y., Elisseeva, O. A., Tsuboi, A., et al. (2000) Human cytotoxic T-lymphocyte responses specific forpeptides of the wild-type Wilms’ tumor gene (WT1) product. Immunogenetics 51, 99–107.
PubMed CAS Google Scholar
Reddy, P., Teshima, T., Hildebrandt, G., et al. (2002) Interleukin 18 preserves aperforindependent graft-versus-leukemia effect after allogeneic bone marrow transplantation. Blood 100, 3429–3431.
PubMed CAS Google Scholar
Brahmi, Z., Hommel-Berrey, G., Smith, F., and Thomson, B. (2001) NK cells recover early and mediate cytotoxicity via perforin/granzyme and Fas/FasL pathways in umbilical cord blood recipients. Hum. Immunol. 62, 782–790.
PubMed CAS Google Scholar
Susskind, B., Shornick, M. D., Iannotti, M. R., et al. (1996) Cytolytic effector mechanisms of human CD4+cytotoxic T lymphocytes. Hum. Immunol. 45, 64–75.
PubMed CAS Google Scholar
Kunitomi, A., Hori, T., Maeda, M., and Uchiyama, T. (2002) OX40 signaling renders adult T-cell leukemia cells resistant to Fas-induced apoptosis. Intl. J. Hematol. 76, 260–266.
CAS Google Scholar
Liu, J. H., Wei, S., Lamy, T., et al. (2002) Blockade of Fas-dependent apoptosis by soluble Fas in LGL leukemia. Blood 100, 1449–1453.
PubMed CAS Google Scholar
Schmaltz, C., Alpdogan, O., Horndasch, K. J., et al. (2001) Differential use of Fas ligand and perforin cytotoxic pathways by donor T cells in graft-versus-host disease and graftversus-leukemia effect. Blood 97, 2886–2895.
PubMed CAS Google Scholar
Tanaka, Y., Takahashi, T., Nieda, M., et al. (2002) Generation of Fas-independent CD4+cytotoxic T-cell clone specific for p190 minor bcr-abl fusion peptide. Leukemia Res. 26, 317–321.
CAS Google Scholar
Schmaltz, C., Alpdogan, O., Muriglan, S. J., et al. (2003) Donor T cell-derived TNF is required for graft-versus-host disease and graft-versus-tumor activity after bone marrow transplantation. Blood 101, 2440–2445.
PubMed CAS Google Scholar
Schmaltz, C., Alpdogan, O., Kappel, B. J., et al. (2002) T cells require TRAIL for optimal graft-versus-tumor activity. Nat. Med. 8, 1433–1437.
PubMed CAS Google Scholar
Middleton, P. G., Taylor, P. R., Jackson, G., Proctor, S. J., and Dickinson, A. M. (1998) Cytokine gene polymorphisms associating with severe acute graft-versus-host disease in HLA-identical sibling transplants. Blood 92, 3943–3948.
PubMed CAS Google Scholar
Nordlander, A., Uzunel, M., Mattsson, J., and Remberger, M. (2002) The TNFd4 allele is correlated to moderate-to-severe acute graft-versus-host disease after allogeneic stem cell transplantation. Br. J. Haematol. 119, 1133–1136.
PubMed Google Scholar
Dickinson, A. M., Cavet, J., Cullup, H., Wang, X. N., Sviland, L., and Middleton, P. G. (2001) GvHD risk assessment in hematopoietic stem cell transplantation: role of cytokine gene polymorphisms and an in vitro human skin explant model. Hum. Immunol. 62, 1266–1276.
PubMed CAS Google Scholar
Cavet, J., Dickinson, A. M., Norden, J., Taylor, P. R., Jackson, G. H., and Middleton, P. G. (2001) Interferon-gamma and interleukin-6 gene polymorphisms associate with graft-versus-host disease in HLA-matched sibling bone marrow transplantation. Blood 98, 1594–1600.
PubMed CAS Google Scholar
Warle, M. C., Farhan, A., Metselaar, H. J., et al. (2002) Cytokine gene polymorphisms and acute human liver graft rejection. Liver Transplant. 8, 603–611.
Google Scholar
Mazariegos, G. V., Reyes, J., Webber, S. A., et al. (2002) Cytokine gene polymorphisms in children successfully withdrawn from immunosuppression after liver transplantation. Transplantation 73, 1342–1345.
PubMed CAS Google Scholar
Awad, M. R., Webber, S., Boyle, G., et al. (2001) The effect of cytokine gene polymorphisms on pediatric heart allograft outcome. J. Heart Lung Transplant. 20, 625–630.
PubMed CAS Google Scholar
Poole, K. L., Gibbs, P. J., Evans, P. R., Sadek, S. A., and Howell, W. M. (2001) Influence of patient and donor cytokine genotypes on renal allograft rejection: evidence from a single centre study. Transplant Immunol. 8, 259–265.
CAS Google Scholar

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Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA
William J. Hogan & Hans Joachim Deeg

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William J. Hogan
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Hans Joachim Deeg
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Research Department, Kantonsspital St. Gallen, Switzerland
Burkhard Ludewig
Department of Abdominal and Transplant Surgery, Hannover Medical School, Hannover, Germany
Matthias W. Hoffmann

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Hogan, W.J., Deeg, H.J. (2005). Stem Cell Transplantation: Graft-Mediated Antileukemia Effects. In: Ludewig, B., Hoffmann, M.W. (eds) Adoptive Immunotherapy: Methods and Protocols. Methods in Molecular Medicine™, vol 109. Humana Press. https://doi.org/10.1385/1-59259-862-5:421

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DOI: https://doi.org/10.1385/1-59259-862-5:421
Publisher Name: Humana Press
Print ISBN: 978-1-58829-406-7
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