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Interleukin-2 in Bone Marrow Transplantation

  • Udit N. Verma
  • Bishan S. Charak
  • Chitra Rajagopal
  • Amitabha Mazumder
Part of the Cancer Treatment and Research book series (CTAR, volume 76)

Abstract

Interleukin 21 (IL-2) is a 15 kD protein that was initially known as T-cell growth factor [1], IL-2 stimulates the proliferation of T cells both in vitro and in vivo. Incubation of lymphocytes with IL-2 in vitro results in the generation of cells referred to as lymphokine activated killer (LAK) cells, which lyse fresh noncultured tumor cells in a histocompatibility unrestricted manner [2–4]. LAK cells show killing effects both in vitro and in vivo of a wide variety of tumors [2–4]. Recent studies [5,6] have shown that LAK cells are comprised of T cells as well as natural killer (NK) cells. Other cells, such as macrophages, probably also play a role in regulating the generation of LAK cells.

Keywords

Acute Myeloid Leukemia Graft Versus Host Disease Lymphokine Activate Killer Lymphokine Activate Killer Cell Cytotoxic Effector Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Smith KA: Interleukin-2: Inception, impact, and implications. Science 240:1169–1176, 1988.PubMedCrossRefGoogle Scholar
  2. 2.
    Lotze MT, Line BR, Mathisen DJ, et al.: The in vivo distribution of autologous human and murine lymphoid cells grown in T cell growth factor (TCGF): Implication for the adoptive immunotherapy of tumors. J Immunol 125:1487–1493, 1980.PubMedGoogle Scholar
  3. 3.
    Grimm EA, Mazumder A, Zhang HZ, Rosenberg SA: Lymphokine-activated killer cell phenomenon. Lysis of natural killer-resistant fresh solid tumor cells by interleukin-2 activated autologous human peripheral blood lymphocytes. J Exp Med 155:1823–1841, 1982.Google Scholar
  4. 4.
    Rayner AA, Grimm EA, Lotze MT, et al.: Lymphokine activated killer (LAK) cell phenomenon. IV. Lysis by LAK cell clones of fresh human tumor cells from autologous and multiple allogeneic tumors. J Natl Cancer Inst 75:67–75, 1985.PubMedGoogle Scholar
  5. 5.
    Kalland T, Belfrage H, Bhiladvala P, Hedlund G: Analysis of the murine lymphokine activated killer (LAK) cell phenomenon: Dissection of effectors and progenitors into NK-and T-like cells. J Immunol 138:3640–3645, 1987.PubMedGoogle Scholar
  6. 6.
    Chadwick BS, Miller RG: Heterogeneity of the lymphokine-activated killer cell phenotype. Cell Immunol 132:168–176, 1991.PubMedCrossRefGoogle Scholar
  7. 7.
    Lotze MT, Chang AE, Seipp CA, Simpson CG, Vetto JT, Rosenberg SA: High dose recombinant-2 in the treatment of patients with disseminated cancer. JAMA 256:3117–3124, 1986.PubMedCrossRefGoogle Scholar
  8. 8.
    Rosenberg SA, Lotze MT, Yang JC, et al.: Experience with the use of high dose interleukin-2 in the treatment of 652 cancer patients. Ann Surg 210:474–485, 1989.PubMedCrossRefGoogle Scholar
  9. 9.
    Agah R, Malloy B, Sherrod A, Mazumder A: Successful therapy of natural killer-resistant pulmonary metastases by the synergism of γ-interferon with tumor necrosis factor and interleukin-2 in mice. Cancer Res 48:2245–2248, 1988.PubMedGoogle Scholar
  10. 10.
    Ettinghausen SE, Lipford EH, Mule JJ, et al.: Systemic administration of recombinant interleukin-2 stimulates in vivo lymphoid cell proliferation in tissues. J Immunol 135: 1488–1497, 1985.PubMedGoogle Scholar
  11. 11.
    Ettinghausen SE, Lipford EH, Mule JJ, et al.: Recombinant interleukin-2 stimulates in vivo proliferation of adoptively transferred lymphokine activated killer (LAK) cells. J Immunol 135:3623–3635, 1985.PubMedGoogle Scholar
  12. 12.
    Rosenberg SA: The immunotherapy and gene therapy of cancer. J Clin Oncol 10:180–199, 1992.PubMedGoogle Scholar
  13. 13.
    Rubin JT, Elwood LJ, Rosenberg SA, Lotze MT: Immunohistochemical correlates of response to IL-2 based immunotherapy in humans. Cancer Res 49:7086–7092, 1989.PubMedGoogle Scholar
  14. 14.
    McCulloch P, Gallagher G, Walsh LP, Zaloom Y, Xie J: Lymphokine-activated killer (LAK) cells modulate the effects IL-2 on a T cell mediated immune response. Clin Exp Immunol 85:519–524, 1991.PubMedCrossRefGoogle Scholar
  15. 15.
    Papa MZ, Yang JC, Vetto JT, et al.: Combined effects of chemotherapy and interleukin-2 in the therapy of mice with advanced pulmonary tumors. Cancer Res 48:122–129, 1988.PubMedGoogle Scholar
  16. 16.
    Charak BS, Brynes RK, Groshen S, Chen S-C, Mazumder A: Bone marrow transplantation with interleukin-2-activated bone marrow followed by interleukin-2 therapy for acute myeloid leukemia in mice. Blood 76:2187–2190, 1990.PubMedGoogle Scholar
  17. 17.
    Hamon MD, Prentice HG, Gottlieb DJ, et al.: Immunotherapy with interleukin 2 after ABMT in AML. Bone Marrow Transplant 11:399–401, 1993.PubMedGoogle Scholar
  18. 18.
    Favrot MC, Floret D, Negrier S, et al.: Systemic interleukin-2 therapy in children with progressive neuroblastoma after high dose chemotherapy and bone marrow transplantation. Bone Marrow Transplant 4:499–503, 1989.PubMedGoogle Scholar
  19. 19.
    Gottlieb DJ, Brenner MK, Heslop HE, et al.: A phase I clinical trial of recombinant interleukin 2 following high dose chemo-radiotherapy for hematological malignancy: Applicability to the elimination of minimal residual disease. Br J Cancer 60:810–816, 1990.Google Scholar
  20. 20.
    Blaise D, Olive D, Stoppa AM, et al.: Hematologic and immunologic effects of the systemic administration of recombinant interleukin-2 after autologous bone marrow transplantation. Blood 76:1092–1097, 1990.PubMedGoogle Scholar
  21. 21.
    Higuchi CM, Thompson JA, Peterson FB, Buckner CD, Fefer A: Toxicity and immuno-modulatory effects of interleukin-2 after autologous bone marrow transplantation for hematologie malignancies. Blood 77:2561–2568, 1991.PubMedGoogle Scholar
  22. 22.
    Soiffer RJ, Murray C, Cochran K, et al.: Clinical and immunologie effects of prolonged infusion of low-dose recombinant interleukin-2 after autologous and T-cell-depleted allogeneic bone marrow transplantation. Blood 79:517–526, 1992.PubMedGoogle Scholar
  23. 23.
    Adler A, Chervenick PA, Whiteside TL, Lotzova E, Herberman RB: Interleukin-2 induction of lymphokine-activated killer (LAK) cell activity in the peripheral blood and bone marrow of acute leukemia patients: I. Feasibility of LAK generation in adult patients with active disease and in remission. Blood 71:706–716, 1988.Google Scholar
  24. 24.
    Thompson JA, Peace DJ, Klarnet JP, Kern DE, Greenberg PD, Cheever MA: Eradication of disseminated murine leukemia by treatment with high dose interleukin-2. J Immunol 137:3675–3680, 1986.PubMedGoogle Scholar
  25. 25.
    Charak BS, Brynes RK, Chogyoji M, Mazumder A: Lymphokine-activated killer cells in autologous bone marrow transplantation. Evidence against inhibition of engraftment in vivo. Transplantation 54:1008–1013, 1992.Google Scholar
  26. 26.
    Foa R, Meloni G, Tosti S, et al.: Treatment of residual disease in acute leukemia patients with recombinant interleukin 2 (IL2): Clinical and biological findings. Bone Marrow Transplant 6(Suppl l):98–102, 1990.PubMedGoogle Scholar
  27. 27.
    Komori T, Sugiyama H, Ogawa H, et al.: Treatment of a patient in a relapse after bone marrow transplantation for acute lymphoblastic leukemia with the systemic administration of allogeneic lymphokine activated killer cells and recombinant IL-2. Eur J Haematol 43:184–185, 1989.Google Scholar
  28. 28.
    Dickinson AM, Lennard AL, Cartner R, Proctor SJ: Interleukin-2 induction of lymphokine-activated killer activity in the peripheral blood of an acute lymphoblastic leukemia patient — case study. Leukemia 6:957–960, 1992.PubMedGoogle Scholar
  29. 29.
    Weisdorf DJ, Anderson PM, Blazar BR, Uckun FM, Kersey JH, Ramsay NKC: Interleukin 2 immediately after autologous bone marrow transplantation for acute lymphoblastic leukemia — a phase I study. Transplantation 55:61–66, 1993.PubMedCrossRefGoogle Scholar
  30. 30.
    Papa MZ, Mule JJ, Rosenberg SA: Antitumor efficacy of lymphokine-activated killer cells and recombinant interleukin-2 in vivo: Successful immunotherapy of established pulmonary metastases from weakly immunogenic and nonimmunogenic murine tumors of three distinct histological types. Cancer Res 46:4973–4978, 1986.PubMedGoogle Scholar
  31. 31.
    Peace DJ, Cheever MA: Toxicity and therapeutic efficacy of high dose interleukin-2. In vivo infusion of an antibody to NK-1.1 attenuates toxicity without compromising efficacy against murine leukemia. J Exp Med 169:161–173, 1989.PubMedCrossRefGoogle Scholar
  32. 32.
    Fefer A, Benyunes M, Higuchi C, York A, Massumoto C, Lingren C, Buckner CD, Thompson JA: Interleukin-2 ± lymphocytes as consolidative immunotherapy after autologous bone marrow transplantation for hematologie malignancies. Acta Hematol 89(Suppl l):2–7, 1993.CrossRefGoogle Scholar
  33. 33.
    Benyunes MC, Massumoto C, York A, et al.: Interleukin-2 with or without lymphokine-activated killer cells as consolidative immunotherapy after autologous bone marrow transplantation for acute myelogenous leukemia. Bone Marrow Transplant 12:159–163, 1993.PubMedGoogle Scholar
  34. 34.
    Fujimori Y, Hara H, Nagai K: Effect of lymphokine activated killer cell fraction on the development of human hematopoietic progenitor cells. Cancer Res 48:534–538, 1987.Google Scholar
  35. 35.
    van den Brink MRM, Voogt PJ, Marijt WAF, van Luxemburg-Heys SAP, Van Rood JJ, Brand AA: Lymphokine activated killer cells selectively kill tumor cells in bone marrow without compromising bone marrow stem cell function in vitro. Blood 74:354–560, 1989.PubMedGoogle Scholar
  36. 36.
    Charak BS, Malloy B, Agah R, Mazumder A: A novel approach to purging of leukemia by activation of bone marrow with interleukin-2. Bone Marrow Transplant 6:193–198, 1990.Google Scholar
  37. 37.
    Schaafsma MR, Fibbe WE, van der Harst D, et al.: Increased numbers of circulating hematopoietic progenitor cells after treatment with high dose interleukin-2 in cancer patients. Br J Haematol 76:180–185, 1990.PubMedCrossRefGoogle Scholar
  38. 38.
    Heslop HE, Bello-Fernandez C, Reittie JE, et al.: Interleukin 2 infusion after autologous bone marrow transplantation or chemotherapy enhances hematopoietic regeneration. Blood 76(Suppl 1):544, 1990.Google Scholar
  39. 39.
    Bosly AC, Staquet PJ, Doyen CM, Chatelain BJ, Humblet YP, Symann ML: Recombinant human interleukin-2 restores in vitro T-cell colony formation by peripheral blood mononuclear cells after autologous bone marrow transplantation. Exp Hematol 15:1048–1054, 1987.PubMedGoogle Scholar
  40. 40.
    Borradori L, Hirt A, Baumgartner C, Morell A: Influence of exogenous interleukin-2 on the proliferation of lymphocytes from normal donors and from patients after autologous bone marrow transplantation. Acta Haematol 77:129–134, 1987.PubMedCrossRefGoogle Scholar
  41. 41.
    Reittie JE, Gottlieb D, Heslop HE, et al.: Endogenously generated killer cells circulate after autologous and allogeneic bone marrow transplantation but not after chemotherapy. Blood 73:1341–1358, 1989.Google Scholar
  42. 42.
    Bosly A, Guillame T, Brice P, et al.: Effects of escalating doses of recombinant human interleukin-2 in correcting functional T-cell defects following autologous bone marrow transplantation for lymphomas and solid tumors. Exp Hematol 20:962–968, 1992.PubMedGoogle Scholar
  43. 43.
    Heslop HE, Gottlieb DJ, Bianchi ACM, et al.: In vivo induction of y interferon and tumor necrosis factor by interleukin-2 infusin following intensive chemotherapy or autologous bone marrow transplantation. Blood 74:1374–1380, 1989.PubMedGoogle Scholar
  44. 44.
    Massumoto C, Sale G, Benyunes M, et al.: Cutaneous GVHD associated with IL-2 + LAK therapy after autologous bone marrow transplantation (ABMT) for hematologic malignancies. Proc Am Soc Clin Oncol 11:825, 1992.Google Scholar
  45. 45.
    Sprent J, Schaefer M, Gao E, Korngold R: Role of T cell subsets in lethal graft versus host disease (GVHD) directed to class I versus class II H-2 differences. I. L3T4+ cells can either augment or retard GVHD elicited by Lyt-2+ cells in class I different hosts. J Exp Med 167:556–569, 1988.PubMedCrossRefGoogle Scholar
  46. 46.
    Malkovsky M, Brenner MK, Hunt R, et al.: T cell depletion of allogeneic bone marrow prevents acceleration of graft versus host disease induced by exogenous IL-2. Cell Immunol 103:476–480, 1986.Google Scholar
  47. 47.
    Sykes M, Abraham BS, Harty MW, Pearson DA: IL-2 reduces graft-versus-host disease and preserves a graft-versus-leukemia effect by selectively inhibiting CD4+ T cell activity. J Immunol 150:197–205, 1993.PubMedGoogle Scholar
  48. 48.
    Sykes M, Harty MW, Szot GL, Pearson DA: Interleukin-2 inhibits graft versus host disease promoting activity of CD4+ cells while preserving CD4¯ and CD8¯ mediated graft versus leukemia effects. Blood 83:2560–2569, 1994.PubMedGoogle Scholar
  49. 49.
    Azuma E, Kaplan J: Role of lymphokine-activated killer cells as mediators of veto and natural suppression. J Immunol 141:2601–2606, 1988.PubMedGoogle Scholar
  50. 50.
    Nakamura H, Gress RE: Interleukin-2 enhancement of veto suppressor cell function in T-cell-depleted bone marrow in vitro and in vivo. Transplantation 49:931–937, 1990.PubMedCrossRefGoogle Scholar
  51. 51.
    Sykes M, Romick ML, Sachs DH: Interleukin-2 prevents graft-versus-host disease while preserving the graft-versus-leukemia effect of allogeneic T cells. Proc Natl Acad Sci USA 87:5633–5637, 1990.PubMedCrossRefGoogle Scholar
  52. 52.
    Margolin K: The clinical toxicities of high-dose interleukin-2: In Atkins MB, Mier JW (eds): Therapeutic Applications of Interleukin-2. Marcel Dekker, New York: pp 331–362.Google Scholar
  53. 53.
    Damle NK, Doyle LV, Bender JR, Bradley EC: Interleukin-2 activated human lymphocytes exhibit enhanced adhesion to normal vascular endothelial cells and cause their lysis. J Immunol 138:1779–1785, 1987.PubMedGoogle Scholar
  54. 54.
    Thompson JA, Biance JA, Benyunes MC, Neubauer MA, Slattery JT, Fefer A: Phase Ib trial of pertoxifylline and ciprofloxacin in patients treated with interleukin-2 and lymphokine-activated killer cell therapy for metastatic renal cell carcinoma. Cancer Res 54:3436–3441, 1994.PubMedGoogle Scholar
  55. 55.
    Numerof RP, Aronson FR, Mier JW: Interleukin-2 stimulates the production of IL-1 alpha and IL-1 beta by human peripheral blood mononuclear cells. J Immunol 141:4250–4557, 1988.PubMedGoogle Scholar
  56. 56.
    Mier JW, Vachino G, Van der Meer J, et al.: Induction of tumor necrosis factor as the mechanism for the febrile response to interleukin-2. J Clin Immunol 8:426–436, 1988.PubMedCrossRefGoogle Scholar
  57. 57.
    Vachino G, Gelfand J, Atkins M, Tamerius J, Demchak P, Mier J: Complement activation in cancer patients undergoing immunotherapy with interleukin-2 (IL-2): Binding of complement and C-reactive protein by IL-2-activated lymphocytes. Blood 78:2505–2513, 1991.PubMedGoogle Scholar
  58. 58.
    Gribben JG, Freedman AS, Neuberg D, et al.: Immunological purging of marrow assessed by PCR before autologous bone marrow transplantation for B cell lymphoma. N Engl J Med 325:1525–1533, 1991.PubMedCrossRefGoogle Scholar
  59. 59.
    Ringden O, Horowitz MM: Graft-versus-leukemia reactions in humans. The Advisory Committee of the International Bone Marrow Transplant Registry. Transplant Proc 21:2989–2992, 1989.Google Scholar
  60. 60.
    Rosenfeld C, Shadduck RK, Przepiorka D, Mangan KF, Colvin M: Autologous bone marrow transplantation with 4-hydroperoxycyclophosphamide purged marrows for acute nonlymphocytic leukemia in late remission or early relapse. Blood 74:1159–1164, 1989.PubMedGoogle Scholar
  61. 61.
    Pole JG, Gee A, Jansen W, Lee C, Gross S: Immunomagnetic purging of bone marrow: A model for negative cell selection. Am J Pediatr Hematol Oncol 12:257–261, 1990.PubMedCrossRefGoogle Scholar
  62. 62.
    Vogler WR, Berdel WE, Olson AC, Winton EF, Heffner LT, Gordon DS: Autologous bone marrow transplantation in acute leukemia with marrow purged with alkyllysophos-pholipids. Blood 80:1423–1429, 1992.PubMedGoogle Scholar
  63. 63.
    Brenner MK, Rill DR, Moen RC, et al.: Gene-marking to trace origin of relapse after autologous bone-marrow transplantation. Lancet 341:85–86, 1993.PubMedCrossRefGoogle Scholar
  64. 64.
    Uckum FM, Kersey JH, Vallera DA, et al.: Autologous bone marrow transplantation in high risk remission T-lineage acute lymphoblastic leukemia using immunotoxins plus 4-hydroperoxycyclophosphamide for marrow purging. Blood 76:1723–1733, 1990.Google Scholar
  65. 65.
    Truitt RL, Horowitz MM, Atasoylu AA, Drobyski WR, Johnson BD, LeFever AV: Graft-versus-leukemia effect of allogeneic bone marrow transplantation: Clinical and experimental aspects of late leukemia relapse. In Stewart THM, Wheelock EF (eds): Cellular Immune Mechanisms and Tumor Dormancy. Boca Raton, FL: CRC Press, PP 111–128, 1992.Google Scholar
  66. 66.
    Horowitz MM, Gale RP, Sondel PM, et al.: Graft-versus-leukemia reactions after bone marrow transplantation. Blood 75:555–562, 1990.PubMedGoogle Scholar
  67. 67.
    Chang WC, Hsiao MH, Pattengale PK: Natural killer cell immunodeficiency in patients with chronic myelogenous leukemia. IV. Interleukin-1 deficiency, gamma-interferon deficiency and the restorative effects of short term culture in the presence of interleukin-2 on natural killer cytotoxicity, natural killer-target binding and production of natural killer cytotoxic factor. Nat Immun Cell Growth Regul 10:57–70, 1991.PubMedGoogle Scholar
  68. 68.
    Mackinnon S, Hows JM, Goldman JM: Induction of in vitro graft-versus-leukemia activity following bone marrow transplantation for chronic myelogenous leukemia. Blood 76: 2037–2045, 1990.PubMedGoogle Scholar
  69. 69.
    Hauch M, Gazzola MV, Small T, et al.: Anti-leukemia potential of interleukin-2 activated natural killer cells after bone marrow transplantation for chronic myelogenous leukemia. Blood 75:2250–2262, 1990.PubMedGoogle Scholar
  70. 70.
    Agah R, Malloy B, Kerner M, Mazumder A: Generation and characterization of IL-2 activated bone marrow cells as a potent graft versus tumor effector in transplantation. J Immunol 143:3039–3099, 1989.Google Scholar
  71. 71.
    Charak BS, Brynes RK, Katsuda S, Groshen S, Chen S-C, Mazumder A: Induction of graft versus leukemia effect in bone marrow transplantation: Dosage and time schedule dependency of interleukin-2 therapy. Cancer Res 51:2015–2020, 1991.PubMedGoogle Scholar
  72. 72.
    Charak BS, Agah R, Gray D, Mazumder A: Interaction of various cytokines with interleukin-2 in the generation of killer cells from human bone marrow: Application in purging of leukemia. Leuk Res 15:801–810, 1991.PubMedCrossRefGoogle Scholar
  73. 73.
    Keever CA, Pekle K, Gazzola MV, Collins NH, Gillio A: NK and LAK activities from human bone marrow progenitors. I. The effects of interleukin-2 and interleukin-1. Cell Immunol 126:211–226, 1990.PubMedCrossRefGoogle Scholar
  74. 74.
    Agah R, Malloy B, Kerner M, Girgis E, Bean P, Twomey P, Mazumder A: Potent graft anti-tumor effect in natural killer-resistant disseminated tumors by transplantation of interleukin-2-activated syngeneic bone marrow in mice. Cancer Res 49:5959–5963, 1989.PubMedGoogle Scholar
  75. 75.
    Lotze MT, Matory YL, Ettinghausen SE, et al.: In vivo administration of purified human interleukin-2: Half life, immunologic effects, and expansion of peripheral lymphoid cells in vivo with recombinant IL-2. J Immunol 135: 2865–2875, 1985.PubMedGoogle Scholar
  76. 76.
    Kedar E, Klein E: Cancer immunotherapy: Are the results discouraging? Can they be improved? Adv Cancer Res 59:245–322, 1992.Google Scholar
  77. 77.
    Mitchell MS: Combining chemotherapy with biological response modifiers in the treatment of cancer. J Natl Cancer Inst 8:1445–1450, 1988.CrossRefGoogle Scholar
  78. 78.
    Charak BS, Brynes RK, Chogyoji M, Kortes V, Tefft M, Mazumder A: Graft versus leukemia effect of interleukin-2-activated bone marrow: Correlation with eradication of residual disease. Transplantation 56:31–37, 1993.PubMedCrossRefGoogle Scholar
  79. 79.
    Charak BS, Agah R, Brynes RK, Chogyoji M, Groshen S, Chen S-C, Mazumder A: Interleukin-2 (IL-2) and IL-2-activated done marrow in transplantation: Evaluation from a clinical perspective. Bone Marrow Transplant 9:479–486, 1992.PubMedGoogle Scholar
  80. 80.
    Coulombel L, Kalousek D, Eaves CJ, Gupta CM, Eaves A: Long-term marrow culture reveals chromosomally normal hematopoietic progenitor cells in patients with Philadelphia chromosome-positive chronic myelogenous leukemia. N Engl J Med 308:1493–1498, 1983.PubMedCrossRefGoogle Scholar
  81. 81.
    Hogge DE, Coulombel L, Kalousek DK, Eaves CJ, Eaves AC: Nonclonal hemopoietic progenitors in a G6PD heterozygote with chronic myelogenous leukemia revealed after long-term marrow culture. Am J Hematol 24:389–394, 1987.PubMedCrossRefGoogle Scholar
  82. 82.
    Coulombel L, Eaves CJ, Kalousek DK, Gupta C, Eaves AC: Long term marrow culture of cells from patients with acute myelogenous leukemia. J Clin Invest 75:961–969, 1985.PubMedCrossRefGoogle Scholar
  83. 83.
    Firkin FC, Birner R, Farag S: Differential action of diffusible molecules in long term culture on proliferation of leukemic and normal hematopoietic cells. Br J Hematol 84:8–15, 1993.CrossRefGoogle Scholar
  84. 84.
    Udomsakdi C, Eaves CJ, Swolin B, Reid DS, Barnett MJ, Eaves AC: Rapid decline of chronic myeloid leukemic cells in long term culture due to a defect at the leukemic stem cell level. Proc Natl Acad Sci USA 89:6192–6196, 1992.PubMedCrossRefGoogle Scholar
  85. 85.
    Lotzova E, Savary CA: Generation of NK cell activity from human bone marrow. J Immunol 139:279–284, 1987.PubMedGoogle Scholar
  86. 86.
    Verma UN, Bagg A, Brown E, Mazumder A: Interleukin-2 activation of human bone marrow in long term cultures: An effective strategy for purging and generation anti-tumor cytotoxic effectors. Bone Marrow Transplant 13:115–123, 1994.PubMedGoogle Scholar
  87. 87.
    Savary CA, Lotzova E: Inhibition of human bone marrow and myeloid progenitors by interleukin-2 activated lymphocytes. Exp Hematol 18:1083–1089, 1990.PubMedGoogle Scholar
  88. 88.
    Cuturi MC, Anegon I, Sherman F, et al.: Production of hematopoietic colony-stimulating factors by human natural killer cells. J Exp Med 169:569–583, 1989.PubMedCrossRefGoogle Scholar
  89. 89.
    Murphy WJ, Keller JR, Harrison CL, Young HA, Longo DL: Interleukin-2 activated natural killer cells can support hematopoiesis in vitro and promote marrow engraftment in vivo. Blood 80:670–677, 1992.PubMedGoogle Scholar
  90. 90.
    Verma UN, Mazumder A: Purging and hematopoietic reconstitution ability of murine bone marrow IL-2 activated in long term cultures. Manuscript in preparation.Google Scholar
  91. 91.
    Klingemann HG, Deal H, Reid D, Eaves CJ: Pre-clinical evaluation of a bone marrow autograft culture procedure for generating lymphokine-activated killer cells in vitro. Can J Infect Dis 3:123B-127B, 1992.Google Scholar
  92. 92.
    Klingemann HG, Deal H, Reid D, Eaves CJ: Design and validation of a clinically applicable culture procedure for the generation of interleukin-2 activated natural killer cells in human bone marrow autografts. Exp Hematol 21:1263–1270, 1993.PubMedGoogle Scholar
  93. 93.
    Long GS, Cramer DV, Harnaha JB, Hiserodt JC: Lymphokine-activated killer (LAK) cell purging of leukemic bone marrow: Range of activity against different hematopoietic neoplasms. Bone Marrow Transplant 6:169–177, 1990.PubMedGoogle Scholar
  94. 94.
    Chao N, Schriber J, Grimes K, et al.: Granulocyte colony-stimulating factor ‘mobilized’ peripheral blood progenitor cells accelerate granulocyte and platelet recovery after high dose chemotherapy. Blood 81:2031–2035, 1993.PubMedGoogle Scholar
  95. 95.
    To LB, Roberts MM, Haylock DN, et al.: Comparison of hematological recovery times and supportive care requirements of autologous recovery phase peripheral blood stem cell Transplants, autologous bone marrow transplants and allogeneic bone marrow transplants. Bone Marrow Transplant 9:277–284, 1992.PubMedGoogle Scholar
  96. 96.
    Kessinger A, Armitage JO: The evolving role of autologous peripheral stem cell transplantation following high-dose therapy for malignancies. Blood 77:211–213, 1991.PubMedGoogle Scholar
  97. 97.
    Kessinger A, Bierman P, Vose J, Armitage JO: High-dose cyclophosphamide, carmustine, and etopside followed by autologous peripheral stem cell transplantation for patients with relapsed Hodgkin’s disease. Blood 77:2322–2325, 1991.PubMedGoogle Scholar
  98. 98.
    Liu K-Y, Akashi K, Harada M, Takamatsu Y, Niho Y: Kinetics of circulating hematopoietic progenitors during chemotherapy-induced mobilization with or without granulocyte colony-stimulating factor. Br J Haematol 84:31–38, 1993.PubMedCrossRefGoogle Scholar
  99. 99.
    Verma UN, Areman E, Dickerson SA, Kotula PL, Sacher R, Mazumder A: Interleukin-2 activation of chemotherapy and growth factor mobilized peripheral blood stem cells for generation of cytotoxic effectors. Bone Marrow Transplant 15:199–206, 1995.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Udit N. Verma
  • Bishan S. Charak
  • Chitra Rajagopal
  • Amitabha Mazumder

There are no affiliations available

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