Seminars in Hematology
Volume 43, Issue 2 , Pages 118-125 , April 2006

Immunologic Approaches to Acute Leukemia in the Elderly

  • Sherif S. Farag

      Affiliations

    • Corresponding Author InformationAddress correspondence to Sherif S. Farag, MD, PhD, The Ohio State University, B312 Starling Loving Hall, 320 W 10th Ave, Columbus, OH 43210.
    • ,
  • Michael A. Caligiuri

References 

  1. Taylor PR , Reid MM , Proctor SJ . Acute lymphoblastic leukaemia in the elderly . Leuk Lymphoma . 1994;13:373–380
  2. Mayer RJ , Davis RB , Schiffer CA , Berg DT , Powell BL , Schulman P , et al.   Intensive postremission chemotherapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B . N Engl J Med . 1994;331:896–903
  3. Stone RM , Berg DT , George SL , Dodge RK , Paciucci PA , Schulman PP , et al.   Postremission therapy in older patients with de novo acute myeloid leukemia (A randomized trial comparing mitoxantrone and intermediate-dose cytarabine with standard-dose cytarabine) . Blood . 2001;98:548–553
  4. Pagano L , Mele L , Casorelli I , Fianchi L , Di Febo A , Leone G . Acute lymphoblastic leukemia in the elderly. A twelve-year retrospective, single center study . Haematologica . 2000;85:1327–1329
  5. Bertz H , Potthoff K , Finke J . Allogeneic stem-cell transplantation from related and unrelated donors in older patients with myeloid leukemia . J Clin Oncol . 2003;21:1480–1484
  6. Alyea EP , Kim HT , Ho V , Cutler C , Gribben J , DeAngelo DJ , et al.   Comparative outcome of nonmyeloablative and myeloablative allogeneic hematopoietic cell transplantation for patients older than 50 years of age . Blood . 2005;105:1810–1814
  7. Landay AL , Zarcone D , Grossi CE , Bauer K . Relationship between target cell cycle and susceptibility to natural killer lysis . Cancer Res . 1987;47:2767–2770
  8. Allavena P , Damia G , Colombo T , Maggioni D , D’Incalci M , Mantovani A . Lymphokine-activated killer (LAK) and monocyte-mediated cytotoxicity on tumor cell lines resistant to antitumor agents . Cell Immunol . 1989;120:250–258
  9. Trinchieri G . Biology of natural killer cells . Adv Immunol . 1989;47:187–376
  10. Cooper MA , Fehniger TA , Turner SC , Chen KS , Ghaheri BA , Ghayur T , et al.   Human natural killer cells (A unique innate immunoregulatory role for the CD56(bright) subset) . Blood . 2001;97:3146–3151
  11. Caligiuri MA , Zmuidzinas A , Manley TJ , Levine H , Smith KA , Ritz J . Functional consequences of interleukin 2 receptor expression on resting human lymphocytes. Identification of a novel natural killer cell subset with high affinity receptors . J Exp Med . 1990;171:1509–1526
  12. Baume DM , Robertson MJ , Levine H , Manley TJ , Schow PW , Ritz J . Differential responses to interleukin 2 define functionally distinct subsets of human natural killer cells . Eur J Immunol . 1992;22:1–6
  13. Caligiuri MA , Murray C , Robertson MJ , Wang E , Cochran K , Cameron C , et al.   Selective modulation of human natural killer cells in vivo after prolonged infusion of low dose recombinant interleukin 2. J Clin . Invest . 1993;91:123–132
  14. Nagler A , Lanier LL , Phillips JH . Constitutive expression of high affinity interleukin 2 receptors on human CD16-natural killer cells in vivo . J Exp Med . 1990;171:1527–1533
  15. Robertson MJ , Soiffer RJ , Wolf SF , Manley TJ , Donahue C , Young D , et al.   Response of human natural killer (NK) cells to NK cell stimulatory factor (NKSF) (Cytolytic activity and proliferation of NK cells are differentially regulated by NKSF) . J Exp Med . 1992;175:779–788
  16. Mrozek E , Anderson P , Caligiuri MA . Role of interleukin-15 in the development of human CD56+ natural killer cells from CD34+ hematopoietic progenitor cells . Blood . 1996;87:2632–2640
  17. Fehniger TA , Caligiuri MA . Interleukin 15 (Biology and relevance to human disease) . Blood . 2001;97:14–32
  18. Freud AG , Becknell B , Roychowdhury S , Mao HC , Ferketich AK , Nuovo GJ , et al.   A human CD34(+) subset resides in lymph nodes and differentiates into CD56bright natural killer cells . Immunity . 2005;22:295–304
  19. Shimizu Y , DeMars R . Demonstration by class I gene transfer that reduced susceptibility of human cells to natural killer cell-mediated lysis is inversely correlated with HLA class I antigen expression . Eur J Immunol . 1989;19:447–451
  20. Lanier LL . Activating and inhibitory NK cell receptors . Adv Exp Med Biol . 1998;452:13–18
  21. Lopez-Botet M , Bellon T , Llano M , Navarro F , Garcia P , de Miguel M . Paired inhibitory and triggering NK cell receptors for HLA class I molecules . Hum Immunol . 2000;61:7–17
  22. Lopez-Botet M , Llano M , Navarro F , Bellon T . NK cell recognition of non-classical HLA class I molecules . Semin Immunol . 2000;12:109–119
  23. Ljunggren HG , Karre K . In search of the ‘missing self’ (MHC molecules and NK cell recognition) . Immunol Today . 1990;11:237–244
  24. Zijlstra M , Auchincloss H , Loring JM , Chase CM , Russell PS , Jaenisch R . Skin graft rejection by beta 2-microglobulin-deficient mice . J Exp Med . 1992;175:885–893
  25. Moretta A , Bottino C , Pende D , Tripodi G , Tambussi G , Viale O , et al.   Identification of four subsets of human CD3-CD16+ natural killer (NK) cells by the expression of clonally distributed functional surface molecules (Correlation between subset assignment of NK clones and ability to mediate specific alloantigen recognition) . J Exp Med . 1990;172:1589–1598
  26. Malnati MS , Lusso P , Ciccone E , Moretta A , Moretta L , Long EO . Recognition of virus-infected cells by natural killer cell clones is controlled by polymorphic target cell elements . J Exp Med . 1993;178:961–969
  27. Braud VM , Allan DS , O’Callaghan CA , Soderstrom K , D’Andrea A , Ogg GS , et al.   HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C . Nature . 1998;391:795–799
  28. Pende D , Parolini S , Pessino A , Sivori S , Augugliaro R , Morelli L , et al.   Identification and molecular characterization of NKp30, a novel triggering receptor involved in natural cytotoxicity mediated by human natural killer cells . J Exp Med . 1999;190:1505–1516
  29. Cantoni C , Bottino C , Vitale M , Pessino A , Augugliaro R , Malaspina A , et al.   NKp44, a triggering receptor involved in tumor cell lysis by activated human natural killer cells, is a novel member of the immunoglobulin superfamily . J Exp Med . 1999;189:787–796
  30. Pessino A , Sivori S , Bottino C , Malaspina A , Morelli L , Moretta L , et al.   Molecular cloning of NKp46 (A novel member of the immunoglobulin superfamily involved in triggering of natural cytotoxicity) . J Exp Med . 1998;188:953–960
  31. Bauer S , Groh V , Wu J , Steinle A , Phillips JH , Lanier LL , et al.   Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA . Science . 1999;285:727–729
  32. Bahram S . MIC genes (From genetics to biology) . Adv Immunol . 2000;76:1–60
  33. Sutherland CL , Chalupny NJ , Schooley K , VandenBos T , Kubin M , Cosman D . UL16-binding proteins, novel MHC class I-related proteins, bind to NKG2D and activate multiple signaling pathways in primary NK cells . J Immunol . 2002;168:671–679
  34. Pende D , Cantoni C , Rivera P , Vitale M , Castriconi R , Marcenaro S , et al.   Role of NKG2D in tumor cell lysis mediated by human NK cells (Cooperation with natural cytotoxicity receptors and capability of recognizing tumors of nonepithelial origin) . Eur J Immunol . 2001;31:1076–1086
  35. Groh V , Rhinehart R , Randolph-Habecker J , Topp MS , Riddell SR , Spies T . Costimulation of CD8alphabeta T cells by NKG2D via engagement by MIC induced on virus-infected cells . Nat Immunol . 2001;2:255–260
  36. Farag SS , George SL , Lee EJ , Baer M , Dodge RK , Becknell B , et al.   Postremission therapy with low-dose interleukin 2 with or without intermediate pulse dose interleukin 2 therapy is well tolerated in elderly patients with acute myeloid leukemia (Cancer and Leukemia Group B study 9420) . Clin Cancer Res . 2002;8:2812–2819
  37. Middleton D , Curran M , Maxwell L . Natural killer cells and their receptors . Transplant Immunol . 2002;10:147–164
  38. Farag SS , Fehniger TA , Ruggeri L , Velardi A , Caligiuri MA . Natural killer cell receptors (New biology and insights into the graft-versus-leukemia effect) . Blood . 2002;100:1935–1947
  39. Maraninchi D , Vey N , Viens P , Stoppa AM , Archimbaud E , Attal M , et al.   A phase II study of interleukin-2 in 49 patients with relapsed or refractory acute leukemia . Leuk Lymphoma . 1998;31:343–349
  40. Meloni G , Foa R , Vignetti M , Guarini A , Fenu S , Tosti S , et al.   Interleukin-2 may induce prolonged remissions in advanced acute myelogenous leukemia . Blood . 1994;84:2158–2163
  41. Meloni G , Vignetti M , Andrizzi C , Capria S , Foa R , Mandelli F . Interleukin-2 for the treatment of advanced acute myelogenous leukemia patients with limited disease (updated experience with 20 cases) . Leuk Lymphoma . 1996;21:429–435
  42. Olive D , Chambost H , Sainty D , Stoppa AM , Blaise D , el Marsafy S , et al.   Modifications of leukemic blast cells induced by in vivo high-dose recombinant interleukin-2 . Leukemia . 1994;8:1230–1235
  43. Lim SH , Newland AC , Kelsey S , Bell A , Offerman E , Rist C , et al.   Continuous intravenous infusion of high-dose recombinant interleukin-2 for acute myeloid leukaemia—A phase II study . Cancer Immunol Immunother . 1992;34:337–342
  44. Meloni G , Vignetti M , Pogliani E , Ivernizzi R , Allione B , Mirto S , et al.   Interleukin-2 therapy in relapsed acute myelogenous leukemia . Cancer J Sci Am . 1997;3:S43–S47
  45. Bergmann L , Heil G , Kolbe K , Lengfelder E , Puzicha E , Martin H , et al.   Interleukin-2 bolus infusion as late consolidation therapy in 2nd remission of acute myeloblastic leukemia . Leuk Lymphoma . 1995;16:271–279
  46. Wiernik PH , Dutcher JP , Todd M , Caliendo G , Benson L . Polyethylene glycolated interleukin-2 as maintenance therapy for acute myelogenous leukemia in second remission . Am J Hematol . 1994;47:41–44
  47. Sievers EL , Lange BJ , Sondel PM , Krailo MD , Gan J , Liu-Mares W , et al.   Feasibility, toxicity, and biologic response of interleukin-2 after consolidation chemotherapy for acute myelogenous leukemia (A report from the Children’s Cancer Group) . J Clin Oncol . 1998;16:914–919
  48. Fefer A , Benyunes M , Higuchi C , York A , Massumoto C , Lindgren C , et al.   Interleukin-2 +/- lymphocytes as consolidative immunotherapy after autologous bone marrow transplantation for hematologic malignancies . Acta Haematol . 1993;89:2–7
  49. Benyunes MC , Massumoto C , York A , Higuchi CM , Buckner CD , Thompson JA , 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 . 1993;12:159–163
  50. Massumoto C , Benyunes MC , Sale G , Beauchamp M , York A , Thompson JA , et al.   Close simulation of acute graft-versus-host disease by interleukin-2 administered after autologous bone marrow transplantation for hematologic malignancy . Bone Marrow Transplant . 1996;17:351–356
  51. Robinson N , Benyunes MC , Thompson JA , York A , Petersdorf S , Press O , et al.   Interleukin-2 after autologous stem cell transplantation for hematologic malignancy (A phase I/II study) . Bone Marrow Transplant . 1997;19:435–442
  52. Meehan KR , Badros A , Frankel SR , Cahill R , Areman E , Jenson M , et al.   A pilot study evaluating interleukin-2-activated hematopoietic stem cell transplantation for hematologic malignancies . J Hematother . 1997;6:457–464
  53. Benyunes MC , Higuchi C , York A , Lindgren C , Thompson JA , Buckner CD , et al.   Immunotherapy with interleukin 2 with or without lymphokine-activated killer cells after autologous bone marrow transplantation for malignant lymphoma (A feasibility trial) . Bone Marrow Transplant . 1995;16:283–288
  54. Caligiuri MA , Murray C , Soiffer RJ , Klumpp TR , Seiden M , Cochran K , et al.   Extended continuous infusion low-dose recombinant interleukin-2 in advanced cancer (Prolonged immunomodulation without significant toxicity) . J Clin Oncol . 1991;9:2110–2119
  55. Bernstein ZP , Porter MM , Gould M , Lipman B , Bluman EM , Stewart CC , et al.   Prolonged administration of low-dose interleukin-2 in human immunodeficiency virus-associated malignancy results in selective expansion of innate immune effectors without significant clinical toxicity . Blood . 1995;86:3287–3294
  56. Bernstein ZP , Khatri V , Poiesz B . Phase I/II study of daily subcutaneous (sc) low dose interleukin-2 (IL-2) in AIDS-associated lymphomas (AIDS-NHL) . Blood . 1998;92:625a; (abstr)
  57. Fehniger TA , Bluman EM , Porter MM , et al.   Potential mechanisms of human natural killer cell expansion in vivo during low-dose IL-2 therapy . J Clin Invest . 2000;106:117–124
  58. Farag SS , George SL , Lee EJ , Mrozek E , Cooper MA , VanDeusen JB , et al.   Postremission therapy with low-dose interleukin 2 with or without intermediate pulse dose interleukin 2 therapy is well tolerated in elderly patients with acute myeloid leukemia (Cancer and Leukemia Group B study 9420) . Clin Cancer Res . 2002;8:2812–2819
  59. Cortes JE , Kantarjian HM , O’Brien S , Giles F , Keating MJ , Freireich EJ , et al.   A pilot study of interleukin-2 for adult patients with acute myelogenous leukemia in first complete remission . Cancer . 1999;85:1506–1513
  60. Ganser A , Heil G , Seipelt G , Hofmann W , Fischer JT , Langer W , et al.   Intensive chemotherapy with idarubicin, ara-C, etoposide, and m-AMSA followed by immunotherapy with interleukin-2 for myelodysplastic syndromes and high-risk Acute Myeloid Leukemia (AML) . Ann Hematol . 2000;79:30–35
  61. Blaise D , Attal M , Reiffers J , Michallet M , Bellanger C , Pico JL , et al.   Randomized study of recombinant interleukin-2 after autologous bone marrow transplantation for acute leukemia in first complete remission . Eur Cytokine Network . 2000;11:91–98
  62. Mizoguchi H , O’Shea JJ , Longo DL , Loeffler CM , McVicar DW , Ochoa AC . Alterations in signal transduction molecules in T lymphocytes from tumor-bearing mice . Science . 1992;258:1795–1798
  63. Kono K , Salazar-Onfray F , Petersson M , Hansson J , Masucci G , Wasserman K , et al.   Hydrogen peroxide secreted by tumor-derived macrophages down-modulates signal-transducing zeta molecules and inhibits tumor-specific T cell-and natural killer cell-mediated cytotoxicity . Eur J Immunol . 1996;26:1308–1313
  64. Hansson M , Asea A , Ersson U , Hermodsson S , Hellstrand K . Induction of apoptosis in NK cells by monocyte-derived reactive oxygen metabolites . J Immunol . 1996;156:42–47
  65. Hansson M , Hermodsson S , Brune M , Mellqvist UH , Naredi P , Betten A , et al.   Histamine protects T cells and natural killer cells against oxidative stress . J Interferon Cytokine Res . 1999;19:1135–1144
  66. Johansson S , Landstrom M , Hellstrand K , Henriksson R . The response of Dunning R3327 prostatic adenocarcinoma to IL-2, histamine and radiation . Br J Cancer . 1998;77:1213–1219
  67. Hellstrand K , Naredi P , Lindner P , Lundholm K , Rudenstam CM , Hermodsson S , et al.   Histamine in immunotherapy of advanced melanoma (A pilot study) . Cancer Immunol Immunother . 1994;39:416–419
  68. Agarwala SS , Glaspy J , O’Day SJ , Mitchell M , Gutheil J , Whitman E , et al.   Results from a randomized phase III study comparing combined treatment with histamine dihydrochloride plus interleukin-2 versus interleukin-2 alone in patients with metastatic melanoma . J Clin Oncol . 2002;20:125–133
  69. Brune M , Castaigne S , Catalano J , Kurt Gehlsen , Wolf-Karsten Hofmann , Anthony Ho , et al.   Improved leukemia-free survival after post-consolidation treatment with histamine hydrochloride and interleukin-1 in AML (A randomized phase III trial) . Blood . 2004;104:261; (abstr)
  70. Handgretinger R , Lang P , Schumm M , Pfeiffer M , Gottschling S , Demirdelen B , et al.   Immunological aspects of haploidentical stem cell transplantation in children . Ann N Y Acad Sci . 2001;938:340–357
  71. Wetzler M , Baer MR , Stewart SJ , Donohue K , Ford L , Stewart CC , et al.   HLA class I antigen cell surface expression is preserved on acute myeloid leukemia blasts at diagnosis and at relapse . Leukemia . 2001;15:128–133
  72. Clynes RA , Towers TL , Presta LG , Ravetch JV . Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets . Nat Med . 2000;6:443–446
  73. Kono K , Takahashi A , Ichihara F , Sugai H , Fujii H , Matsumoto Y . Impaired antibody-dependent cellular cytotoxicity mediated by herceptin in patients with gastric cancer . Cancer Res . 2002;62:5813–5817
  74. Costello RT , Sivori S , Marcenaro E , Lafage-Pochitaloff M , Mozziconacci MJ , Reviron D , et al.   Defective expression and function of natural killer cell-triggering receptors in patients with acute myeloid leukemia . Blood . 2002;99:3661–3667
  75. Dabholkar M , Tatake R , Amin K , Advani S , Gangal S . Modulation of natural killer and antibody-dependent cellular cytotoxicity by interferon and interleukin-2 in chronic myeloid leukemia patients in remission . Oncology . 1989;46:123–127
  76. Carson WE , Parihar R , Lindemann MJ , Personeni N , Dierksheide J , Meropol NJ , et al.   Interleukin-2 enhances the natural killer cell response to Herceptin-coated Her2/neu-positive breast cancer cells . Eur J Immunol . 2001;31:3016–3025
  77. Friedberg JW , Neuberg D , Gribben JG , Fisher DC , Canning C , Koval M , et al.   Combination immunotherapy with rituximab and interleukin 2 in patients with relapsed or refractory follicular non-Hodgkin’s lymphoma . Br J Haematol . 2002;117:828–834
  78. Caron PC , Co MS , Bull MK , Avdalovic NM , Queen C , Scheinberg DA . Biological and immunological features of humanized M195 (anti-CD33) monoclonal antibodies . Cancer Res . 1992;52:6761–6767
  79. Linenberger ML . CD33-directed therapy with gemtuzumab ozogamicin in acute myeloid leukemia (Progress in understanding cytotoxicity and potential mechanisms of drug resistance) . Leukemia . 2005;19:176–182
  80. Feldman EJ , Brandwein J , Stone R , Kalaycio M , Moore J , O’Connor J , et al.   Phase III randomized multicenter study of a humanized anti-CD33 monoclonal antibody, lintuzumab, in combination with chemotherapy, versus chemotherapy alone in patients with refractory or first-relapsed acute myeloid leukemia . J Clin Oncol . 2005;23:4110–4116
  81. Kossman SE , Scheinberg DA , Jurcic JG , Jimenez J , Caron PC . A phase I trial of humanized monoclonal antibody HuM195 (anti-CD33) with low-dose interleukin 2 in acute myelogenous leukemia . Clin Cancer Res . 1999;5:2748–2755
  82. Koh CY , Blazar BR , George T , Welniak LA , Capitini CM , Raziuddin A , et al.   Augmentation of antitumor effects by NK cell inhibitory receptor blockade in vitro and in vivo . Blood . 2001;97:3132–3137
  83. Ruggeri L , Capanni M , Casucci M , Volpi I , Tosti A , Perruccio K , et al.   Role of natural killer cell alloreactivity in HLA-mismatched hematopoietic stem cell transplantation . Blood . 1999;94:333–339
  84. Miller JS , Soignier Y , Panoskaltsis-Mortari A , McNearney SA , Yun GH , Fautsch SK , et al.   Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer . Blood . 2005;105:3051–3057

PII: S0037-1963(06)00023-0

doi: 10.1053/j.seminhematol.2006.01.006

Seminars in Hematology
Volume 43, Issue 2 , Pages 118-125 , April 2006

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