Klinische Wochenschrift

, Volume 61, Issue 19, pp 947–954 | Cite as

Immunotherapy in the treatment of acute myelogenous leukemia (AML): Rationale, results and future prospects

  • D. Urbanitz
  • Th. Büchner
  • H. Pielken
  • J. van de Loo
Originalien
Received:
Accepted:

Summary

Patients with AML in complete remission (CR) are immunosuppressed; remission lymphocytes of at least a part of the patients are able to recognize autologous leukemic blasts; the CR represents a minimal residual disease. Thus, important conditions for a potentially successful active immunotherapy are given. Results of most earlier randomized trials on immunotherapy revealed some, but limited benefit with respect to survival. Encouraging effects, however, have been achieved by immunizing CR patients with high-dose neuraminidase-treated allogeneic blasts. Because these data have not been confirmed until now we recently initiated a randomized study utilizing identical treatment protocols. The preliminary results of the ongoing study still do not allow to draw any firm conclusions. Specific monoclonal antibodies or autologous cytotoxic T-cells may be useful tools for future immunotherapy of AML.

Key words

Acute myelogenous leukemia Immunological parameters Results of immunotherapy 
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References

  1. 1.
    Al-Rammahy AK, Shipman S, Jackson A, Malcolm A, Levy JG (1980) Evidence for a common leukemia-associated antigen in acute myelogenous leukemia. Cancer Immunol Immunother 9:181–185Google Scholar
  2. 2.
    Baker MA, Falk JA, Taub RN (1978) Immunotherapy of human acute leukemia: antibody response to leukemia-associated antigens. Blood 52:469–480PubMedGoogle Scholar
  3. 3.
    Baldwin RW, Robins RA (1976) Factors interfering with immunological rejection of tumors. Br Med Bull 32:118–123PubMedGoogle Scholar
  4. 4.
    Bates SE, Suen JY, Tranum BL (1979) Immunological skin testing and interpretation. A plea for uniformity. Cancer 43:2306–2314PubMedGoogle Scholar
  5. 5.
    Bekesi JG, Arneault GSt, Walter L, Holland JF (1972) Immunogenicity of Leukemia L1210 cells after neuraminidase treatment. J Natl Cancer Inst 49:107–118PubMedGoogle Scholar
  6. 6.
    Bekesi JG, Roboz IP, Zimmermann E, Holland JF (1976) Treatment of spontaneous leukemia in AKR mice with chemotherapy, immunotherapy and interferon. Cancer Res 36:631–639PubMedGoogle Scholar
  7. 7.
    Bekesi JG, Holland JF, Fleminger R, Yates J, Henderson ES (1977) Immunotherapeutic efficacy of neuraminidase-treated allogeneic myeloblasts in patients with acute myelocytic leukemia. In: Chirigos MA (ed) Control of Neoplasia by modulation of the Immune System, pp 573–592Google Scholar
  8. 8.
    Bekesi JG, Holland JF (1979) Impact of specific immunotherapy in acute myelocytic leukemia. In: Neth R, Gallo RC, Hofschneider HP, Mannweiler K (eds) Modern trends in human leukemia III. Springer, Berlin Heidelberg New York, pp 79–87Google Scholar
  9. 9.
    Blume KG, Beutler E, Bross KJ, Chillar RK, Ellington OB, Fahey JL, Farbstein MJ, Forman StJ, Schmidt GM, Scott EP, Spruce WE, Turner MA, Wolf JL (1980) Bonemarrow ablation and allogeneic marrow transplantation in acute leukemia. N Engl J Med 302:1041–1046PubMedGoogle Scholar
  10. 10.
    Büchner T, Urbanitz D, Hiddemann W, Kamanbroo D, Meister R, Balleisen L, Delvos U, Lagrcze EM, Schmitz-Huebner U, Schulte H, van de Loo J (1979) Intensification of remission induction therapy for acute nonlymphocytic leukemia (ANLL). Blut 39:133–140PubMedGoogle Scholar
  11. 11.
    Büchner T, Urbanitz D, Emmerich B, Fischer JT, Fülle HH, Heinecke A, Hoßfeld DK, Koeppen KM, Labedzki L, Löffler H, Nowrousian MR, Pfreundschuh M, Pralle H, Rühl H, Wendt FC for the AML Cooperative Group (1982) Multicenter Study on Intensified Remission Induction Therapy for Acute Myeloid Leukemia. Leukemia Research, 6:827–831PubMedGoogle Scholar
  12. 12.
    Carcassone Y, Favre R, Sebahoun G, Gartaut JA, Imbert-Xeridot L (1977) Chemo-immunotheray done in maintenance treatment of acute non-lymphoblastic leukemia. In: Mandelli F (ed) Therapy of acute leukemia. Lombardo editore, Roma, pp 715–722Google Scholar
  13. 13.
    Chan P, Wiernik PH, Lichtenfeld JL (1978) Levamisole, cytosine-arabinoside (ara-c), and daunorubicin (DNR) induction therapy of adult acute non-lymphocytic leukemia (ANLL). Proc Am Assoc Cancer Res Am Soc Clin Oncol 19:370Google Scholar
  14. 14.
    Cocks P, Powles RL, Chapuis B, Alcxander P (1977). Further evidence of response by leukemia patients in remission to antigen(s) related to acute myelogenous leukemia. Br J Cancer 35:273–279PubMedGoogle Scholar
  15. 15.
    Eppinger-Helft M, Pavlovsky S, Hidalgo G, Sackmann Muriel F, Suarez A, Garay G, Russo C, Santos M, Macchi A, Lein J (1980) Chemoimmunotherapy with corynebacterium parvum in acute myelocytic leukemia. Cancer 45:280–284PubMedGoogle Scholar
  16. 16.
    Ezaki K, Hersh EM, Keating M, Dyre S, Hollinshead A, McCredie KB, Mavligit GM, Gutterman JU (1978) Active specific immunization with allogeneic leukemia associated antigens or irradiated allogeneic leukemia cells in acute leukemia. Cancer 41:70–83PubMedGoogle Scholar
  17. 17.
    Gale RP, Cline MJ (1977) High remission induction rate in acute myeloid leukemia. Lancet I:497–499Google Scholar
  18. 18.
    Gale RP (1979) Advances in the treatment of acute myelogenous lcukemia. N Engl J Med 300:1189–1192PubMedGoogle Scholar
  19. 19.
    Galton DAG, Kay HEM, Reizenstein P, Penchansky M, Vogler WR, Whittaker JA (1977) Infection and second-remission rates in patients having immunotherapy for acute myeloid leukemia. Lancet I:973Google Scholar
  20. 20.
    Galton DA, Peto R (1978) Immunotherapy of acute myeloid leukaemia. Br J Cancer 37:1–14PubMedGoogle Scholar
  21. 21.
    Granatek CH, Ezaki K, Hersh EM, Keating MJ, Rasmussen S (1981) Antibody responses of remission leukemia patients receiving active specific and nonspecific immunotherapy. Cancer 47:272–279PubMedGoogle Scholar
  22. 22.
    Gutterman JU, Rodriguez V, Mavligit G, Burgess MA, Gehan E, Hersh EM, McCredie KB, Reed R, Smith T, Bodey GP, Freireich EJ (1974) Chemoimmunotherapy of adult acute leukemia prolongation of remission in myeloblastic leukaemia with B.C.G. Lancet II:1406–1409Google Scholar
  23. 23.
    Harris R, Zuhrie SR, Freeman CB, Tayler GM, MacIvery JE, Geary CG, Delamore IW, Hull PJ, Tooth JA (1978) Active Immunotherapy in acute myelogenous leukaemia and the induction of second and subsequent remissions. Br J Cancer 37:282–288PubMedGoogle Scholar
  24. 24.
    Haubeck HD, Kölsch E (1983) Induction of specific T suppressor cells to the BALB/C plasmocytoma ADJ-PC-5 during carly stages of tumorigenesis. Immunology (in press)Google Scholar
  25. 25.
    Kano K, Nishimake T, Palosuo T, Loza K, Milgrom F (1978) Detection of circulating immune-complexes by the inhibition of antibody. Clin Immunol Immunopathol 9:425–435PubMedGoogle Scholar
  26. 26.
    Kuntz MM, Innes JB, Weksler ME (1976) Lymphocyte transformation induced by autologous cells. J Exp Med 143:1042–1046PubMedGoogle Scholar
  27. 27.
    Lindemalm ChS, Killander A, Björkholm M, Brenning G, Engstedt L, Franzen L, Gahrton G, Gullbring B, Holm G, Höglund S, Hörnsten P, Jameson S, Killander D, Klein E, Lantz B, Lockner D, Lönnqvist B, Mellstedt H, Palmbad J, Pauli C, Reizenstein P, Simonsson B, Skarberg KO, Uden AM, Vanky F, Wadman B (1978) Adjuvant Immunotherapy in acute nonlymphocytic leukemia. Cancer Immunol Immunother 4:179–183Google Scholar
  28. 28.
    Mandelli F, Amadori S, Dini E, Grignani F, Leonis P, Liso V, Martelli M, Neri A, Petti MC, Ferrini PR (1981) Randomized clinical trial of immunotherapy and androgenotherapy for remission maintenance in acute non-lymphocytic leukemia. Leukemia Res 5:447–452Google Scholar
  29. 29.
    Mathé G, Pouillart P, Lapeyraque F (1969) Active immunotherapy of L 1210 leukemia applied after the graft of tumor cells. Br J Cancer 23:814–824PubMedGoogle Scholar
  30. 30.
    McCredie KB, Bodey GP, Freireich EJ, Hester JP, Rodriguez V, Keating MJ (1981) Chemoimmunotherapy of adult acute leukemia. Cancer 47:1256–1261PubMedGoogle Scholar
  31. 31.
    Miller RA, Maloney DG, Warnke R, Levy R (1982) Treatment of B-cell lymphoma with monoclonal anti-idiotype antibody. N Engl J Med 306:517–522PubMedGoogle Scholar
  32. 32.
    MRC Report (1978) Immunotherapy of acute myeloid leukaemia. Br J Cancer 37:1–14Google Scholar
  33. 33.
    Murphy S, Hersh E (1978) Immunotherapy of leukemia and lymphoma. Semin Hematol 15:181–203PubMedGoogle Scholar
  34. 34.
    Omura GA, Vogler WR, Lefante J, Silberman H, Knospe W, Gordon D, Jarrell R (1982) Treatment of acute myelogenous leukemia: Influence of three induction regimens and maintenance with chemotherapy or BCG immunotherapy. Cancer 49:1530–1536PubMedGoogle Scholar
  35. 35.
    Pauli C, Vanky F, Hast R, Lindemalm C, Uden AM, Reizenstein P (1978) Cell-mediated immunity in human acute myeloblastic leukemia. Cancer Immunol Immunother 5:1–10Google Scholar
  36. 36.
    Peterson BA, Bloomfield CD, Bosl GJ, Gibbs G, Malloy M (1980) Intensive five-drug combination chemotherapy for adult acute non-lymphocytic leukemia. Cancer 46:663–668PubMedGoogle Scholar
  37. 37.
    Pincus JH, Jameson AK, Brandt AE (1981) Immunotherapy of L1210 Leukemia using neuraminidase-modified plasma membranes combined with chemotherapy. Cancer Res 41:3082–3086PubMedGoogle Scholar
  38. 38.
    Powles RL, Russel J, Lister TA, Oliver T, Whitehouse JMA, Malpas J, Chapuis B, Crowther D, Alexander P (1977) Immunotherapy for acute myelogenous leukemia: a controlled clinical study 2 1/2 years after entry of the last patient. Br J Cancer 35:265–272PubMedGoogle Scholar
  39. 39.
    Preissler HD, Rustum Y, Henderson ES, Bjornsson S, Creaven PJ, Higby DJ, Freeman A, Gailani S, Naeher C (1979) Treatment of acute nonlymphocytic leukemia: Use of anthracycline-cytosine arabinoside induction therapy and comparison of two maintenance regimens. Blood 53:454–464Google Scholar
  40. 40.
    Rees JKH, Hayhoe FGL (1981) The treatment of acute myeloid leukemia (AML) — Some factors affecting the success rate. VI. Meeting Intern Soc Haematol Eur Afric Div Abstr 232Google Scholar
  41. 41.
    Rees JKH, Sandler RM, Cahllener J, Hayhoe FGJ (1977) Treatment of acute myeloid leukacmia with a triple cytotoxic regime: DAT. Br J Cancer 36:770–776PubMedGoogle Scholar
  42. 42.
    Rühl H, Fülle HH, Koeppen KM, Schwerdtfeger R (1981) Adjuvant specific immunotherapy in maintenance treatment of adult acute non-lymphocytic leukemia. Klin Wochenschr 59:1189–1193PubMedGoogle Scholar
  43. 43.
    Schuepbach J, Sauter C (1981) Inverse correlation of antiviral antibody titers and the remission length in patients treated with viral oncolysate: A possible new prognostic sign in acute myelogenous leukemia. Cancer 48:1363–1367PubMedGoogle Scholar
  44. 44.
    Skipper HE, Schabel FM, Trader MW, Laster WR (1969) Response to therapy of spontaneous, first passage, and long passage lines of ak leukemia. Cancer Chemother Rep 53:345–366PubMedGoogle Scholar
  45. 45.
    Sulitzeanu D, Weiss DW (1981) Antigen and Immunogen — A question of terminology. Cancer Immunol Immunother 11:291–292Google Scholar
  46. 46.
    Thomas ED, Buckner CD, Clift RA, Fefer A, Johnson FL, Neiman PE, Sale GE, Sanders JE, Singer JW, Shulman H, Storb R, Weiden PL (1979) Marrow transplantation for acute nonlymphoblastic leukemia in first remission. N Engl J Med 301:597–599PubMedGoogle Scholar
  47. 47.
    Uden AM, Lindemalm C, Pauli C, Vanky F, Reizenstein P (1978) Effects of immunotherapy and chemotherapy on immunocompetence. A study of patients with acute myeloblastic leukemia in remission. Cancer Immunol Immunother 4:239–245Google Scholar
  48. 48.
    Urbanitz D, Büchner Th, Kamanabroo D, Hiddemann W, Schulte H, van de Loo J (1981) Intensified remission induction therapy for acute nonlymphocytic leukemia (ANLL) Treatment report on 60 patients. Blut 43:129–133PubMedGoogle Scholar
  49. 49.
    Vogler WR, Chan YK (1974) Prolonging remission in myeloblastic leukaemia by tice-strain bacillus Calmette-Guerin. Lancet I:128–131Google Scholar
  50. 50.
    Vogler WR, Gordon DS, Smalley RV, Heffner ThJ, Trulock P, Guzman G, Barbieri B, Hearn E (1981a) Serial immunologic assessment during a randomized trial of chemoimmunotherapy in acute myelogenous leukemia. Cancer Immunol Immunother 11:97–107Google Scholar
  51. 51.
    Vogler WR (1981b) Results of randomized trials of immunotherapy for acute leukemia. Cancer Immunol Immunother 9:15–21Google Scholar
  52. 52.
    Vuvan H, Fiere D, Doillon M, Martin C, Coiffier B, Felman P, Bryon PA, Favre-Gilly J, Revol L (1978) BCG therapy in acute non lymphoid leukaemias. Scand J Haematol 21:40–46PubMedGoogle Scholar
  53. 53.
    Weinstein HJ, Mayer RJ, Rosenthal DS, Camitta BM, Coral FS, Nathan DG, Frei III E (1980) Treatment of acute myelogenous leukemia in children and adults. N Engl J Med 303:473–478PubMedGoogle Scholar
  54. 54.
    Whiteside MG, Cauchi MN, Paton Ch, Stone J (1976) Chemoimmunotherapy for maintenance in acute myeloblastic leukemia. Cancer 38:1581–1586PubMedGoogle Scholar
  55. 55.
    Whittaker JA, Bailey-Wood R, Hutchins S (1980) Active immunotherapy for the treatment of acute myelogenous leukaemia: report of two controlled trials. Br J Haematol 45:389–400PubMedGoogle Scholar
  56. 56.
    Whittaker JA, Reizenstein P, Callender ST, Cornwell GG, Delamore IW, Gale RP, Gobbi M, Jacobs P, Lantz B, Maiolo AT, Rees JKH, van Slyck EJ, Vu Van H (1981) Long survival in acute myelogenous leukaemia: an international collaborative study. Br Med J 282:692–695Google Scholar
  57. 57.
    Wiernik PH, Holland JF, Rai J, Cuttner J, Ellison RR, Glidewell O, Wesley M (1981) Comparison of bone marrow transplantation (BMT) with chemotherapy alone (CT) for remission maintenance in acute myelogenous leukemia (AML). ASCO (Abstr) 484Google Scholar
  58. 58.
    Zarling JM, Bach FA (1979) Continous culture of T-cells cytotoxic for autologous leukemia cells. Nature 280:685–689PubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH & Co KG 1983

Authors and Affiliations

  • D. Urbanitz
    • 1
  • Th. Büchner
    • 1
  • H. Pielken
    • 1
  • J. van de Loo
    • 1
  1. 1.Med. Univ.-KlinikMünsterGermany

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