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Role of interleukin-2 in human hematological malignancies

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Abstract

Clinical studies with Interleukin-2 (IL-2) in human hematologic malignancies were initiated in the late 1980s. Based on clinical studies on various solid tumors, and laboratory research on hematopoietic cells, IL-2 was shown to be effective in 150 acute myeloid leukemia (AML) patients mainly for maintenance therapy in first complete remission, or with residual blast cells in the marrow. IL-2 has also been shown to be effective in remission induction in 10 patients with chronic myeloid leukemia (CML). The role of IL-2 in lymphoma patients remains to be established. IL-2 alone or in combination with Interferon-α, may intensify remission and prolong disease-free survival when given post autologous bone marrow transplantation (BMT) to patients with lymphoma and myeloid leukemia, and to a lesser degree, to patients with acute lymphatic leukemia (ALL). IL-2 in combination with HLA-matched or mismatched peripheral blood lymphocytes was also used post autologous BMT in preliminary studies. IL-2 was administered with or without peripheral blood lymphocytes, for prevention of relapse post T-cell-depleted allogeneic BMT in CML, ALL and AML, with encouraging results. The same strategy was shown to be effective in the reinduction of remission in patients with CML, who relapsed post BMT.

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References

  1. Parkinson, D.R. (1988) Interleukin-2 in cancer therapy.Sem. Oncol. 15, 10–8.

    CAS  Google Scholar 

  2. Robb, R.J. and Greene, W.C. (1983) Direct demonstration of the identity of T cell growth factor binding protein and the TAC antigen.J. Exp. Med. 158, 1332.

    Article  PubMed  CAS  Google Scholar 

  3. Smith, K.A. (1980) T cell growth factor.Immunol. Rev. 51, 337.

    Article  PubMed  CAS  Google Scholar 

  4. Waldman, T.A. (1986) The structure, function and expression of IL-2 receptor on normal and malignant lymphocytes.Science 232, 727.

    Article  Google Scholar 

  5. Dower, S.K., Kefeneider, S.H., Alpert, A.R. and Urdal, D.L. (1985) Quantitive measurements of human interleukin-2 receptor levels with intact and detergent solubilized human T-cells.Mol. Immunol. 22(8), 937.

    Article  PubMed  CAS  Google Scholar 

  6. Lowenthal, J.W., Zubler, R.H., Nabholz, M. and Macdonald, H.R. (1985) Similarities between interleukin-2 receptors number and affinity on activated B and T lymphocytes.Nature 315, 669.

    Article  PubMed  CAS  Google Scholar 

  7. Tsudo, M., Uchiyama, T. and Uchino, H. (1984) Expression of Tac antigen on activated normal human B cells.J. Exp. Med. 160, 612.

    Article  PubMed  CAS  Google Scholar 

  8. Waldman, T.A., Goldman, C.K. and Robb, R.J. (1984) Expression of interleukin 2 receptors on activated human B cells.J. Exp. Med. 160, 1450.

    Article  Google Scholar 

  9. Nagler, A., Lanier, L.L. and Phillips, J.H. (1990) Constitutive expression of high affinity interleukin 2 receptors on human CD16- natural killer cellsin vivo.J. Exp. Med. 171, 1527–33.

    Article  PubMed  CAS  Google Scholar 

  10. Rosenberg, S.A. (1989) Clinical immunotherapy studies in the surgery of the US National Cancer Institute: brief review:Can. Treat. Rev. 16(A), 115.

    Article  Google Scholar 

  11. Rosenberg, S.A. (1984) Immunotherapy of cancer by systemic administration of lymphoid cells plus interleukin-2. A review.J. Biol. Response Mod. 3, 501.

    PubMed  CAS  Google Scholar 

  12. Rosenberg, S.A., Spiess, P. and Lafreniere, R. (1986) A new approach to the adoptive immunotherapy of cancer with tumor infiltrating lymphocytes.Science 223, 1318.

    Article  Google Scholar 

  13. Rosenberg, S.A., Lotze, M.T. and Muul, L.M. (1987) A progress report on the treatment of 157 patients with advanced cancer using lymphokine activated killer cells and interleukin-2 and high dose interleukin-2 alone.N. Engl. J. Med. 316, 889.

    PubMed  CAS  Google Scholar 

  14. West, W.H., Tawer, K.W. and Yannelli, J.R. (1987) Constant infusion of recombinant interleukin-2 in adoptive immunotherapy of advanced cancer.N. Engl. J. Med. 316, 898.

    PubMed  CAS  Google Scholar 

  15. Lissoni, P., Meregalli, S., Fossati, V., Paolorossi, J., Barni, S., Tancini, G. and Frigerio, F. (1994) A randomized study of immunotherapy with low dose subcutaneous interleukin-2 plus melatonin vs chemotherapy with cisplatin and etoposide as first line therapy for advanced non-small cell lung cancer.Tumori 80(6), 464–7.

    PubMed  CAS  Google Scholar 

  16. Su, N., Ojeifo, J., MacPherson, A. and Zwiebel, J. (1994) Breast cancer gene therapy: transgenic immunotherapy.Breast Cancer Res. Treat. 31, 349–56.

    Article  PubMed  CAS  Google Scholar 

  17. Vujanovic, N.L., Yasumura, S., Hirabayashi, H., Lin, W.C., Watkins, S., Herberman, R.B. and Whiteside, T.L. (1995) Antitumor activities of subsets of human IL-2-activated natural killer cells in solid tissues.J. Immunol. 154(1), 281–9.

    PubMed  CAS  Google Scholar 

  18. Lotzova, E., Savary, C.A. and Herberman, R.B. (1987) Induction of NK cell activity against fresh human leukemia in culture with interleukin-2.J. Immunol. 138, 2718.

    PubMed  CAS  Google Scholar 

  19. Gottleib, D.J., Brenner, M.K., Heslop, H.E., Bello-Fernandez, C., Galazka, A. and Prentice, H.G. (1989) Effects of rIL-2 administration on cytotoxic function following high dose chemoradiotherapy for hematologic malignancy.Blood 74, 2337.

    Google Scholar 

  20. Broxmeyer, H.E., Williams, D.E., Lu, L., Cooper, S., Anderson, S.L., Beyer, G.S., Hoffman, R. and Rubbin, Y.Y. (1986) The suppressive influences of human tumor necrosis factor on bone marrow hematopoietic progenitor cells from normal donors and patients with leukemia: Synergism of tumor necrosis factor and interferon-gamma.J. Immunol. 136, 4487.

    PubMed  CAS  Google Scholar 

  21. Price, G., Brenner, M.K., Prentice, H.G., Hoffbrand, A.V. and Newland, A.C. (1987) Cytotoxic effects of tumor necrosis factor and gamma interferon on acute myeloid leukemia blast cells.Br. J. Cancer 55, 287.

    PubMed  CAS  Google Scholar 

  22. Morecki, S., Revel-Vilk, S., Nabet, C., Pick, M., Ackerstein, A., Nagler, A., Naparstek, E., Ben-Shahar, M. and Slavin, S. (1992) Immunological evaluation of patients with hematological malignancies receiving ambulatory cytokine-mediated immunotherapy with recombinant human interferon-α2a and interleukin-2.Cancer Immunol. Immunother. 35, 401–41.

    Article  PubMed  CAS  Google Scholar 

  23. Morecki, S., Nagler, A., Puyesky, Y., Nabet, C., Condiotti, R., Pick, M., Gan, S. and Slavin, S. (1993) Effect of various cytokine combinations on induction of non-MHC restricted cytotoxicity.Lymphok. Cytok. Res. 12(3), 159–65.

    CAS  Google Scholar 

  24. Nagler, A., Greenberg, P.L., Lanier, L.L. and Phillips, J.H. (1988) The effects of interleukin 2 activated natural killer cells on autologous peripheral blood hematopoietic progenitors.J. Exp. Med. 168, 47–54.

    Article  PubMed  CAS  Google Scholar 

  25. Foa, R., Caretto, P., Fierro, M.T., Bonferroni, M., Cardona, S., Guarini, A., Lista, P., Pegoraro, L., Mandelli, F., Forni, G. and Gavosto, F. (1990) Interleukin 2 does not promote the in vitro proliferation and growth of human acute leukemia cells of myeloid and lymphoid origin.Br. J. Haematol. 75, 34.

    Article  PubMed  CAS  Google Scholar 

  26. Meloni, G., Foa, R., Vignetti, M., Guarini, A., Fenu, S., Tosi, S., Gillotos, A. and Mandelli, F. (1994) Interleukin-2 may induce prolonged remission in advanced acute myeloid leukemia.Blood 84(7), 2158.

    PubMed  CAS  Google Scholar 

  27. Maraninchi, D., Blaise, D., Viens, P., Brandely, M., Olive, D., Lopez, M., Sainty, D., Marit, G., Stoppa, A.M., Reiffers, J., Gratecos, N., Bertau-Perez, P., Mannoni, P., Mawas, C., Hercend, T., Sebahoun, G. and Carcassonne, Y. (1991) High dose recombinant interleukin-2 and acute myeloid leukemia in relapse.Blood 78(9), 2182.

    PubMed  CAS  Google Scholar 

  28. Wiernik, P.H., Dutcher, J.P., Todd, M., Caliendo, G. and Benson, L. (1994) Polyethylene glycolated interleukin-2 as a maintenance therapy for acute myelogenous leukemia in second remission.Am. J. Hematol. 47, 41–4.

    Article  PubMed  CAS  Google Scholar 

  29. Bergman, L., Jahn, L.B., Heil, H., Kolbe, K. and Lengfelder, E. (1993) Interleukin-2 inverts remission in 2nd remission of AML. The anti-leukemic effect may be caused by specific CD+ cytotoxic lymphocytes.Proc. Am. Ass. Cancer Res. 34, 198 (1182) (Abstr.).

    Google Scholar 

  30. Oken, M.M. and Mazza, J.J. (1991) Maintenance low dose ara-c improves complete remission from salvage induction therapy for relapsed refractory acute myeloid leukemia.Proc. Am. Soc. Clin. Oncol. 10, 739 (Abstr.).

    Google Scholar 

  31. Bergmann, L., Fenchel, K., Heil, G., Kolbe, K., Lengfelder, E., Brucher, J., Lohmeyer, J., Mitrou, P.S, and Hoelzer, D. (1993) Interleukin-2 consolidation therapy in patients with 2nd remission of de novo acute myelocytic leukemia — results of a multicenter trial.Blood 82, 130a (Abstr.).

  32. Nagler, A., Ackerstein, A., Barak, V. and Shimon, S. (1994) Treatment of CML with rIL-2 and IFN-τ.J. Hematother. 3, 75–82.

    PubMed  CAS  Google Scholar 

  33. Duggan, D.B., Santarell, M.T., Zamkoff, K., Lichtman, S. and Ellerton, J. (1992) A phase II study of recombinant interleukin-2 with or without recombinant interferon-β in non-Hodgkin’s lymphoma. A study of cancer and leukemia group B.Br. J. Immunother. 12, 115.

    Article  CAS  Google Scholar 

  34. Thomas, E.D. (1963) The role of bone marrow transplantation in the eradication of malignant disease.Cancer 49, 1963.

    Article  Google Scholar 

  35. Gale, R.P. and Champlin, R.E. (1984) How does BMT cure leukemia?Lancet 12, 28.

    Article  Google Scholar 

  36. Slavin, S. and Nagler, A. (1991) New developments in bone marrow transplantation.Curr. Opin. Oncol. 3, 254–71.

    Article  PubMed  CAS  Google Scholar 

  37. Phillips, G.L., Reece, D.E. and Shephered, J.D. (1991) High dose cytarabine and daunorubicin induction and post remission chemotherapy for the treatment of acute myelogenous leukemia in adults.Blood 77, 1429.

    PubMed  CAS  Google Scholar 

  38. Kersey, J.H., Weisdorf, D., Nesbit, M.E., LeBien, T.W., Woods, W.G., McGlave, P.B., Kim, T., Vallera, D.A., Goldman, A.I. and Bostrom, B. (1987) Comparison of autologous and allogeneic bone marrow transplantation for treatment of high-risk refractory acute lymphatic leukemia.N. Engl. J. Med. 317, 461–7.

    PubMed  CAS  Google Scholar 

  39. Weiden, P.L., Fluornoy, N., Thomas, E.D., Prentice, R., Fefer, A., Buckner, C.D. and Storb, R. (1979) Antileukemic effect of graft versus host disease in human recipients of allogeneic marrow grafts.N. Engl. J. Med. 300, 1068.

    PubMed  CAS  Google Scholar 

  40. Sullivan, K.M., Weiden, P.L., Storb, R., Witherspoon, R.P., Fefer, L., Buckner, C.D., Anasetti, C., Appelbaum, F.R., Badger, C., Beatty, P., Bensinger, W., Berenson, R., Bigelow, C., Cheever, M.A., Clift, R., Deeg, H.J., Doney, K., Greenberg, P., Hansen, J.A., Hill, R., Loughran, T., Martin, P., Meiman, P., Petersen, F.B., Sanders, J., Singer, J., Stewart, P. and Thomas, E.D. (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, 1720.

    PubMed  CAS  Google Scholar 

  41. Verdonck, L.F., van Heugten, H.G., Giltay, J. and Franks, C.R. (1991) Amplification of the graft-versus-host effect in man by interleukin-2.Transplantation 51, 1120.

    PubMed  CAS  Google Scholar 

  42. Klingman, H.G. and Phillips, G.L. (1991) Immunotherapy after bone marrow transplantation.Bone Marr. Transpl. 8, 73.

    Google Scholar 

  43. Horowitz, M.M., Gale, R.P., Sondel, P.M., Goldman, J., Kersey, M., Kolb, H.J., Rimm, A.A., Ringden, O., Rozman, C. and Speck, B. (1990) GVL reaction after BMT.Blood 75, 555–62.

    PubMed  CAS  Google Scholar 

  44. Slavin, S., Ackerstein, A., Naparstek, E., Or, R. and Weiss, L. (1990) The GVL phenomenon: is GVH separable from GVHD?Bone Marr. Transpl. 6, 155–61.

    CAS  Google Scholar 

  45. Weiss, L., Weigensberg, M., Moreck, S., Bar, S., Cobbold, S., Waldman, H. and Slavin, S. (1990) Characterization of effector cells of graft versus leukemia following allogeneic bone marrow transplantation in mice inoculated with murine B-cell leukemia.Cancer Immunol. Immunotherapy 31, 236–42.

    Article  CAS  Google Scholar 

  46. Vourka-Kraussis, U., Kraussis, D., Ackerstein, A. and Slavin, S. (1995) Enhancement of GVL effect with rIL-2 following BMT in a murine model for acute myeloid leukemia in SJL/J mice.Exp. Hematol. 23, 202–8.

    Google Scholar 

  47. Cohen, P., Kraussis-Vourka, U., Weiss, L. and Slavin, S. (1993) Spontaneous and IL-2 induced anti-leukemic and anti-host effects against tumor and host-specific alloantigens.J. Immunol. 151, 4803–10.

    PubMed  CAS  Google Scholar 

  48. Sykes, M., Abraham, V.S., Harty, A.W. and Pearson, D.A. (1993) IL-2 reduces graft versus host disease and preserves a graft versus leukemia effect by selectively inhibiting CD4 + T cell activity.J. Immunol. 150, 197–203.

    PubMed  CAS  Google Scholar 

  49. Rindgen, O., Deeg, H.J., Beschorner, W. and Slavin, S. (1987) Effector cells of graft versus host disease, host resistance, and graft versus leukemia effect: Summary of a workshop on bone marrow transplantation.Transpl. Proc. 29(1), 2758–61.

    Google Scholar 

  50. Weiss, L., Reich, S. and Slavin, S. (1990) Effect of cyclosporine A and methylprednisolone on the graft versus leukemia effect across major histocompatibility barriers in mice following allogeneic bone marrow transplantation.Bone Marr. Transpl. 6, 229–33.

    CAS  Google Scholar 

  51. Mehta, J. (1993) Graft versus leukemia reaction in clinical bone marrow transplantation.Leuk. Lymph. 10, 427–32.

    Article  CAS  Google Scholar 

  52. Jones, R.J., Ambinder, R.F., Piatadosi, S. and Santos, G.W. (1991) Evidence of a graft-versus-lymphoma effect associated with allogeneic bone marrow transplantation.Blood 77(3), 649–53.

    PubMed  CAS  Google Scholar 

  53. Shepherd, J.D., Barnet, M.J., Connors, J.M., Spinelli, J.J., Sutherland, H.J., Kingermann, H.G., Nantel, S.H., Reece, D.E., Currie, C.J. and Phillips, G.L. (1993) Allogeneic bone marrow transplantation for poor-prognosis non-Hodgkin’s lymphoma.Bone Marr. Transpl. 12, 591–6.

    CAS  Google Scholar 

  54. Papadopoulos, E.B., Ladanyi, M., Emanuel, D., Mackinnon, S., Boulad, F., Carabasi, M.H., Castro-Malaspina, H., Childs, B.H., Gillio, A.P. and Small, T.N. (1994) Infusion of donor leukocytes to treat Epstein-Bar virus associated lymphoproliferative disorders after allogeneic bone marrow transplantation.N. Engl. J. Med. 330(17), 1231–3.

    Article  Google Scholar 

  55. Chorpra, R., Goldstone, A.H., Pearce, R., Philip, T., Peterson, F., Appelbaum, F. and De vol, E. (1992) Autologous versus allogeneic bone marrow transplantation for non-Hodgkin’s lymphoma: a case controlled analysis of the European Bone Marrow Transplant Group Registry data.J. Clin. Oncol. 10(11), 1690–5.

    Google Scholar 

  56. Nagler, A., Drakos, P., Ackerstein, A., Or, A., Naparstek, E., Kapelushnik, J. and Slavin, S. (1993) Autologous bone marrow transplantation for Hodgkin’s lymphoma and Hodgkin’s disease: The role of immunotherapy.Eur. J. Cancer 29A (Suppl) S 173.

    Google Scholar 

  57. Slavin, S., Naparstek, E., Nagler, A., Ackerstein, A., Drakos, P., Kapelusnik, Y., Brautbar, C. and Or, R. (1993) Cell-mediated immunotherapy (CMI) for the treatment of malignant hematological disease in conjunction with autologous bone marrow transplantation (ABMT)Blood 82, 292a.

  58. Nagler, A., Ackerstein, A., Or, R., Darkos, P., Kapelushnik, Y., Metha, J., Naparstek, E. and Slavin, S. (1992) Adoptive immunotherapy with mismatched allogeneic peripheral blood lymphocytes (PBL) following autologous bone marrow transplantation (ABMT)Exp. Haematol. 20, 705 (Abstr.).

    Google Scholar 

  59. Slavin, S., Or, R., Naparstek, E., Kapelushnik, Y., Weiss, L., Ackerstein, A., Vourka-Karussis, V. and Nagler, A. (1992) Eradication of minimal residual disease (MRD) following ABMT and allogeneic BMT by cytokine-mediated immunotherapy (CMI) and cell-mediated cytokine-activated immunotherapy (CCI) in experimental animals and man.Blood 80, 535a (Abstr.).

  60. Reittie, J.E., Gottlieb, D., Heslop, H.E., Leger, O., Drexler, H.G., Hazelhurst, G., Hoffbrand, A.V., Prentice, H.G. and Brenner, M.K. (1989) Endogenously-generated activated killer cells circulate after autologous and allogeneic marrow transplantation but not after chemotherapy.Blood 73, 1351.

    PubMed  CAS  Google Scholar 

  61. Niederwieser, D., Gastl, G., Rumpold, H., Marth, C., Kraft, D. and Huber, C. (1987) Rapid reappearance of large granular lymphocytes (LGL) with concomitant reconstitution of natural killer (NK) activity after bone marrow transplantation (BMT)Br. J. Haematol. 65, 301.

    Article  PubMed  CAS  Google Scholar 

  62. Welte, K., Ciobanu, N., Moore, M.A., Gulati, S., O’Reilly, R.J. and Mertelsmann, R. (1984) Defective interleukin 2 production and in vitro restoration of defective T lymphocyte proliferation by highly purified interleukin 2.Blood 64, 380.

    PubMed  CAS  Google Scholar 

  63. Higuchi, C.M., Thompson, J.A., Cox, T., Lindgren, C.G., Buckner, C.D. and Fefer, A. (1989) Lymphokine activated killer function following autologous bone marrow transplantation for refractory hematological malignancies.Cancer Res. 49, 5509.

    PubMed  CAS  Google Scholar 

  64. Mori, T., Tsoi, M.S., Gillis, S., Santos, E., Thomas, E.D. and Storb, R. (1983) Cellular interactions in marrow grafted patients. Impairment of cell-mediated lympholysis associated with graft versus host disease and the effect of interleukin-2.J. Immunol. 130, 712.

    PubMed  CAS  Google Scholar 

  65. Ackerstein, A., Kedar, E. and Slavin, S. (1991) Use of recombinant human interleukin-2 in conjunction with syngeneic bone marrow transplantation in mice as a model for control of minimal residual disease in malignant hematologic disorders.Blood 78, 1212.

    PubMed  CAS  Google Scholar 

  66. Fefer, A., Benyunes, M., Higachi, C., York, A., Massumoto, C., Lidgren, C., Buckner, C.D. and Thompson, J.A. (1993) Interleukin-2 +/- lymphocytes as consolidative immunotherapy after ABMT for hematologic malignancies.Acta Hematologica 89(1), 2.

    Google Scholar 

  67. Fefer, A., Benyunes, M., Massumoto, C., Higuchi, C., York, A., Buckner, C.D. and Thompson, Y.A. (1993) Interleukin-2 therapy after ABMT for hematological malignancies.Sem. Oncol. 20(6), 41.

    CAS  Google Scholar 

  68. Kalpholz, L., Ackerstein, A., Goldenhersh, M.A., Vardy, D. and Nagler, A. (1993) Local cutaneous reaction induced by subcutaneous interleukin-2 and interferon-2α immunotherapy following ABMT.Bone Marr. Transpl. 11, 443.

    Google Scholar 

  69. Schechter, D., Nagler, A., Ackerstein, A., Nassar, H., Admon, D., Naparstek, E. and Rein, A.J.J.T. (1992) Recombinant interleukin-2 and interferon alpha immunotherapy following autologous bone marrow transplantation.Cardiology 80, 168.

    Article  PubMed  CAS  Google Scholar 

  70. Fabian, I., Kravtsov, V., Elis, A., Gurevitch, O., Ackerstein, A., Slavin, S. and Nagler, A. (1994) Eosinophils activation in post-autologous Bone Marrow transplanted patients treated with subcutaneous interleukin 2 and interferon-α2A immunotherapy.Leukemia 8(8), 1379–84.

    PubMed  CAS  Google Scholar 

  71. Prentice, H.G., Macdonald, I.D. and Hamon, M.D. (1993) The role of immunotherapy in the treatment of acute myeloblastic leukemia: from allogeneic bone marrow transplantation to the application of interleukin-2.Cancer Treat. Res. 64, 121.

    PubMed  CAS  Google Scholar 

  72. Prentice, H.G. and Hamon, M.D. (1991) Autologous bone marrow transplantation (ABMT) with or without interleukin-2 (IL-2) immunotherapy for patients with acute myeloblastic leukemia (AML) in first remission:Hematologica 76, 55.

    Google Scholar 

  73. Blaise, D., Olive, D., Stoppa, A.M., Viens, P., Pourreau, C., Attal, M., Jasmin, C., Monges, G., Mawas, C., Mannoni, P., Palmer, P., Franks, C., Philips, T. and Maraninchi, D. (1990) Hematologic and immunologic effects of systemic administration of recombinant interleukin-2 after ABMT.Blood 76(6), 1092.

    PubMed  CAS  Google Scholar 

  74. Baumgarten, E., Schmid, H., Pohl, U., Brozoska, J., Siegert, W. and Henze, G. (1994) Low dose interleukin-2 and recombinant interferon-gamma following ABM grafts in pediatric patients with high risk leukemia.Leukemia 8(5), 850.

    PubMed  CAS  Google Scholar 

  75. Weisdorf, D.J., Anderson, P.M., Blazar, B.R., Uckun, F.M., Kersey, J.H. and Ramsay, N.K.C. (1993) Interleukin-2 immediately after ABMT for acute lymphoblastic leukemia- A phase I study.Transplant 55, 61.

    Article  CAS  Google Scholar 

  76. Meloni, G., Foa, R., Tosti, S., Vignetti, M., Mancini, F., Guarini, A., Marchis, D., Gavosto, F. and Mandelli, F. (1992) Autologous bone marrow transplantation followed by interleukin-2 in children with advanced leukemia: A pilot study.Leukemia 6, 780.

    PubMed  CAS  Google Scholar 

  77. Baruchel, A., Michel, G., Bernaudin, F., Lemerle, S., Leblanc, T., Bordigoni, P. and Vilmer, E. (1993) Interleukin-2 (IL-2) after autologous bone marrow transplantation (ABMT) in children with leukemia.Proc. Am. Ass. Can. Res. 34, 464 (Abstr.).

    Google Scholar 

  78. Hale, G., Collold, S. and Waldman, H. (1968) T-cell depletion with campath-1 in allogeneic bone marrow transplantation.Transplantation 45, 753.

    Article  Google Scholar 

  79. Goldman, S., Gale, R., Horowitz, M., Biggs, T.C., Champlin, R.E., Gluckmann, E. and Hoffmann, R.G. (1988) Bone marrow transplantation for chronic myelogenous leukemia in chronic phase: increased risk of relapse associated with T-cell depletion.Ann. Int. Med. 108, 806.

    PubMed  CAS  Google Scholar 

  80. Waldman, H., Polliack, A., Hale, G., Or, R., Cividalli, G., Weiss, L., Weshler, Z., Samuel, S., Manor, D., Brautbar, C., Rachmilewitz, E.A. and Slavin, S. (1984) Elimination of graft-versus host disease by in vitro depletion of alloreactive lymphocytes with a monoclonal rat anti-human lymphocyte antibody (Campath-1).Lancet 2, 483–5.

    Article  Google Scholar 

  81. Slavin, S., Waldman, H., Or, R., Cividalli, G., Naparstek, E., Steiner-Salz, D., Michaeli, J., Galun, E., Weiss, L., Samuel, S., Morecki, S., Bar, S., Brautbar, C., Weshler, Z., Hale, G., Rachmilewitz, E.A. and Reizner, Y. (1985) Prevention of graft versus host disease in allogeneic bone marrow transplantation for leukemia by T-cell depletion in vitro prior to transplantation.Transplant. Proc. 17, 465–67.

    Google Scholar 

  82. Marmont, A.M., Gale, R.P., Butturini, A., Goldman, J.M., Martelli, M.F., Prentice, H.G., Slavin, S., Storb, R., Truitt, R.L. and Van Bekkum, D.W. (1989) T-cell depletion in allogeneic bone marrow transplantation: progress and problems.Hematologica 74, 235–48.

    CAS  Google Scholar 

  83. Weiss, L., Reich, S. and Slavin, S. (1992) Use of recombinant human interleukin-2 in conjunction with bone marrow transplantation as a model for control of minimal residual disease in malignant hematological disorders: Treatment of murine leukemia in conjunction with allogeneic bone marrow transplantation and IL-2 activated cell-mediated immunotherapy.Can. Inv. 10(1), 19.

    Article  CAS  Google Scholar 

  84. Cohen, P., Vourka-Karusis, Y., Weiss, L. and Slavin, S. (1993) Spontaneous and IL-2 induced anti leukemic and anti host effects against tumor-and host specific alloantigens.J. Immunol. 151(9), 4803.

    PubMed  CAS  Google Scholar 

  85. Sykes, M., Romick, M.L. and Sachs, D.M. (1990) Interleukin-2 prevents graft versus host disease while preserving the graft versus leukemia effect of allogeneic T-cells.Proc. Natl. Acad. Sci. USA 87, 5633.

    Article  PubMed  CAS  Google Scholar 

  86. Robert, Y., Soiffer, J., Murray, C., Gonin, R. and Ritz, J. (1994) Effect of low-dose interleukin-2 on disease relapse after T-cell depleted allogeneic bone marrow transplantation.Blood 84(3), 964.

    Google Scholar 

  87. Soiffer, R., Murray, J., Faiclough, B., Alyea, E. and Ritz, J. (1994) Low dose interleukin-2 following T-cell depleted allogeneic BMT for CML.Blood 84(1), (Abstr.) 837.

    Google Scholar 

  88. Van Rhee, F., Feng, L. and Cullis, J.O. (1994) Relapse of chronic myeloid leukemia after allogeneic bone marrow transplant: The case for giving donor leukocyte transfusions before the onset of hematological relapse.Blood 83(11), 3377–83.

    PubMed  Google Scholar 

  89. Naparstek, E., Or, R., Nagler, A., Cividalli, G., Engelhard, D., Aker, M., Gimon, Z., Nanny, N., Sacks, T., Tochner, Z., Weiss, L., Samuel, S., Brautbar, C., Hale, G., Waldman, H., Steinberg, M. and Slavin, S. (1995) T-cell-depleted allogeneic bone marrow transplantation for acute leukemia using Campath-1 antibodies and post-transplant administration of donor’s peripheral blood lymphocytes for prevention of relapse.Br. J. Haemat. 89, 506–15.

    Article  CAS  Google Scholar 

  90. Kolb, H.J., Mittermuller, J., Clemm, C.H., Holler, E., Ledderose, G., Brehn, G., Heim, M. and Wilmans, W. (1990) Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients.Blood 76, 2462–7.

    PubMed  CAS  Google Scholar 

  91. Frassoni, F., Fagioli, F., Sessarego, M., Gualandi, F., Van-Lint, M.T., Lamparelli, T., Occhini, D., Figari, O., Valbonesi, M. and Bacigalupo, A. (1992) The effect of donor leukocyte infusion in patients with leukemia following allogeneic BMT.Exp. Hematol. 20, 712–7.

    Google Scholar 

  92. Bar, B.M.A.M., Schattenberg, A., Mensink, E.J.B.M., Van Kessel, G., Smetser, T.F.C.M., Knops, G.H.J.N., Linders, E.H.P. and De Witte, T. (1993) Donor leukocyte infusions for chronic myeloid leukemia relapsed after allogeneic bone marrow transplantation.J. Clin. Oncol. 11, 513–9.

    PubMed  CAS  Google Scholar 

  93. Porter, D.L., Roth, M.S., McGarigle, C., James, R.N., Ferrara, L.M. and Antin, J.H. (1994) Induction of graft versus host disease as immunotherapy for relapsed chronic myeloid leukemia.N. Engl. J. Med. 330, 100–6.

    Article  PubMed  CAS  Google Scholar 

  94. Slavin, S., Nagler, A., Naparstek, E., Ackerstein, A., Kapelushnik, Y., Samuel, S., Morecki, S., Nabet, C. and Or, R. (1995) Allogeneic cell-mediated immunotherapy of relapsed leukemia following bone marrow transplantation with donor peripheral blood lymphocytes and recombinant human interleukin-2.Exp. Hematol. 23, 787 (Abstr.).

    Google Scholar 

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Toren, A., Ackerstein, A., Slavin, S. et al. Role of interleukin-2 in human hematological malignancies. Med Oncol 12, 177–186 (1995). https://doi.org/10.1007/BF01571195

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