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. 1984 Dec;18(3):149–154. doi: 10.1007/BF00205503

A randomized trial of chemoimmunotherapy of acute nonlymphocytic leukemia in adults using a protein-bound polysaccharide preparation

Ryozo Ohno 1,✉, Kazumasa Yamada 2, Toru Masaoka 3, Toshiteru Ohshima 4, Ichita Amaki 4, Yutaka Hirota 5, Noboru Horikoshi 6, Atsushi Horiuchi 7, Kuniyuki Imai 8, Ikuro Kimura 9, Koichi Kitajima 9, Hiroyuki Nakamura 3, Toru Nakamura 10, Yoshiro Ohta 11, Yasunobu Sakai 8, Mineya Tanaka 7, Kazuo Tsubaki 7, Haruto Uchino 12, Nobuya Ogawa 13, Kiyoji Kimura 5
PMCID: PMC11039289  PMID: 6391658

Abstract

The effect of immunotherapy with a protein-bound polysaccharide preparation termed PSK on remission duration and survival of adults with acute nonlymphocytic leukemia (ANLL) was studied in a prospective randomized cooperative trial. After having achieved complete remission and receiving a consolidation therapy, 73 patients were randomized either to maintenance chemotherapy or to maintenance chemotherapy plus immunotherapy with PSK. Ultimately 36 patients in the chemotherapy group and 31 in the chemoimmunotherapy group were evaluable. Six months after the last entry, immunotherapy with PSK showed a borderline beneficial effect on remission duration (P=0.089) and on duration of survival (P=0.062). When the data were analyzed 12, 18, and 24 months after the last entry there were no significant differences in duration of remission and survival between the two groups. However, analysis of the data of patients who had maintained complete remission for more than 270 days revealed that immunotherapy had a suggestive beneficial effect (P=0.105), prolonging the 50% remission period by 418 days (885 vs 467 days). Thus, immunotherapy with PSK seems to be active in the treatment of adult ANLL when used for maintenance therapy in combination with chemotherapy, especially in patients with a good prognosis.

Keywords: Leukemia, Beneficial Effect, Polysaccharide, Cancer Research, Complete Remission

References

  • 1.Akiyama J, Kawamura T, Gotohda E, Yamada Y, Hosokawa M, Kodama T, Kobayashi H. Immunochemotherapy of transplanted KMT-17 tumor in WKA rats by combination of cyclophosphamide and immunostimulatory protein-bound polysaccharide isolated from Basidiomycetes . Cancer Res. 1977;37:3042. [PubMed] [Google Scholar]
  • 2.Gale RP, Foom KA, Cline MJ. Intensive chemotherapy for acute myelogenous leukemia. Ann Intern Med. 1981;94:753. doi: 10.7326/0003-4819-94-6-753. [DOI] [PubMed] [Google Scholar]
  • 3.Gutterman JU, Hersh EM, Rodriguez V, McCredie KB, Mavligit G, Reed R, Burgess MA, Smith T, Gehan EA, Bodey GPS, Freireich EJ. Chemoimmunotherapy of adult acute leukemia. Prolongation of remission in myeloblastic leukemia with BCG. Lancet. 1974;II:1405. doi: 10.1016/S0140-6736(74)90070-1. [DOI] [PubMed] [Google Scholar]
  • 4.Hamilton-Fairly G. Immunotherapy in the management of myelogenous leukemia. Arch Intern Med. 1976;136:1406. [PubMed] [Google Scholar]
  • 5.Hattori T, Niimoto M, Koh T, Nakano A, Oride M, Takiyama W, Nishimawari K. Post-operative long-term adjuvant immunotherapy with mitomycin-C, PSK and FT-207 in gastric cancer patients. Jpn J Surgery. 1979;9:110. doi: 10.1007/BF02468845. [DOI] [PubMed] [Google Scholar]
  • 6.Kataoka T, Oh-hashi F, Tsukagoshi S, Sakurai Y. Enhanced induction of immune resistance by concanavalin A-bound L1210 vaccine and an immunopotentiator prepared from Coriolus versicolor . Cancer Res. 1977;37:4416. [PubMed] [Google Scholar]
  • 7.Kato Y, Kawashima K, Ohno R, Yamada K. Treatment of adult nonlymphocytic leukemia with BHAC-DMP therapy. Acta Haematol Jpn. 1983;46:1077. [PubMed] [Google Scholar]
  • 8.Kieting NJ, Smith TL, Gehan EA, McCredie KB, Bodey GP, Spitzer G, Hersh E, Gutterman J, Freireich EJ. Factors related to length of complete remission in adult acute leukemia. Cancer. 1980;45:2017. doi: 10.1002/1097-0142(19800415)45:8<2017::aid-cncr2820450806>3.0.co;2-c. [DOI] [PubMed] [Google Scholar]
  • 9.Lindemalm CS, Killander A, Bjorkholm M, Engstedt L, Franzen S, Gahrton G, Gullbring B, Holm G, Hoglund S, Hornstern P, Jameson S, Killander D, Klein E, Lantz B, Lockner D, Lonngvist B, Mellstedt H, Palmblad J, Pauli C, Reizenstein P, Simonsson B, Skarberg K-O, Uden A-M, Vanky F, Wadman B. Adjuvant immunotherapy in acute nonlymphocytic leukemia. Cancer Immunol Immunother. 1978;4:179. [Google Scholar]
  • 10.Mathé G, Amiel JL, Schwarzenberg L, Schneider M, Cattan A, Schlumberger JR, Hayat M, de Vassal F. Active immunotherapy for acute leukemia. Lancet. 1969;I:697. doi: 10.1016/s0140-6736(69)92648-8. [DOI] [PubMed] [Google Scholar]
  • 11.Nagao T, Komatsuda M, Watanabe K, Nozaki H, Yamauchi K, Arimori S. Immunotherapy of acute leukemia and malignant lymphoma with PSK. Gan-to-Kagakuryoho. 1980;7:1483. [Google Scholar]
  • 12.Nomoto K, Yoshikumi C, Matsunaga K, Fujii T, Takeya K. Restoration of antibody-forming capacity by PS-K in tumor-bearing mice. Gann. 1975;66:365. [PubMed] [Google Scholar]
  • 13.Oh-hashi F, Kataoka T, Tsukagoshi S. Effect of combined use of anticancer drugs with a polysaccharide preparation, Krestin, on mouse leukemia P388. Gann. 1978;69:255. [PubMed] [Google Scholar]
  • 14.Ohno R, Imai K, Yokomaku S, Yamada K. Antitumor effect of protein-bound polysaccharide preparation, PS-K, against 3-methylcholanthrene-induced fibrosarcoma in C57BL/6 mice. Gann. 1975;66:679. [PubMed] [Google Scholar]
  • 15.Ohno R, Yokomaku S, Wakayama K, Sugiura S, Imai K, Yamada K. Effect of protein-bound polysaccharide preparation, PS-K, on the immune response of mice to sheep red blood cells. Gann. 1976;67:97. [PubMed] [Google Scholar]
  • 16.Ohno R, Ueda R, Imai K, Kato Y, Watanabe E, Morishima Y, Yokomaku S, Kobayashi M, Takeyma H, Ezaki K, Kawashima K, Hirano M, Ohara K, Kosaki T, Yoshikawa S, Yamada K. A clinical trial of cell wall skeleton of BCG in chemoimmunotherapy of acute leukemia. Gann. 1978;69:179. [PubMed] [Google Scholar]
  • 17.Passe S, Mike V, Mertelsmann R, Gee TS, Clarkson BD. Acute nonlymphocytic leukemia. Prognostic factors in adults. Cancer. 1982;50:1462. doi: 10.1002/1097-0142(19821015)50:8<1462::aid-cncr2820500804>3.0.co;2-1. [DOI] [PubMed] [Google Scholar]
  • 18.Peterson BA, Bloomfield CD, Bosl GJ, Gibbs G, Mallory M. Intensive five-drug combination chemotherapy for adult acute nonlymphocytic leukemia. Cancer. 1980;46:663. doi: 10.1002/1097-0142(19800815)46:4<663::aid-cncr2820460406>3.0.co;2-9. [DOI] [PubMed] [Google Scholar]
  • 19.Powles RL, Crowther D, Bateman CJT, Beard MEL, McElwain TJ, Russell J, Lister TA, Whitehouse JMA, Wrigley PFM, Pike M, Alexander P, Hamilton-Fairley G. Immunotherapy for acute myelogenous leukaemia. Br J Cancer. 1973;34:1558. doi: 10.1038/bjc.1973.162. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Rees JKH, Sandler RM, Challener J, Hayhoe FGJ. Treatment of acute myeloid leukemia with triple cytoxic regime: DAT. Br J Cancer. 1977;36:770. doi: 10.1038/bjc.1977.260. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Reizenstein P, Brenning G, Engstedt L, Franzen S, Gahrton G, Gullbring B, Holm G, Hocker P, Hoglund S, Hornsten P, Jameson S, Killander A, Killander D, Klein E, Lantz B, Lindmaim C, Lockner D, Lonqvust B, Mellstedt H, Palmblad J, Pauli C, Skarberg K-O, Uden A-M, Vanky F, Wadman B. Effect of immunotherapy on survival and remission duration in acute nonlymphatic leukemia. In: Terry WD, Windhorst D, editors. Immunotherapy of cancer: Present status of trials in man. New York: Raven Press; 1977. p. 329. [Google Scholar]
  • 22.Sakita M, Imai H, Kasuga M, Kageyama N, Imaki S, Tamai M, Fujita Y, Majima S. Effect of a protein-bound polysaccharide preparation, PS-K, on dimethyl hydrazine induction of intestinal tumor in rats. Gann. 1983;74:351. [PubMed] [Google Scholar]
  • 23.Terry WD, Windhorst D, editors. Immunotherapy of cancer: Present status of trials in man. New York: Raven Press; 1978. p. 307. [Google Scholar]
  • 24.Tsukagoshi S, Oh-hashi F. Protein-bound polysaccharide preparation, PS-K, effective against mouse sarcoma-180 and rat ascites hepatoma AH-13 by oral use. Gann. 1974;65:557. [PubMed] [Google Scholar]
  • 25.Tsuru S, Oka M, Hatsuse K, Iwasa I, Zinnaka Y, Nomoto K. Effect of PSK against immunosuppressive factors in the serum of patients with gastric cancer. Igakunoayumi. 1981;119:932. [Google Scholar]
  • 26.Uzuka Y, Lion SK, Yamagata S. Treatment of adult acute leukemia using intermittent combination chemotherapy with daunomycin, cytosine arabinoside, 6-mercaptopurine and prednisolone — DCMP two-step therapy. Tohoku J Exp Med. 1979;118:212. doi: 10.1620/tjem.118.suppl_217. [DOI] [PubMed] [Google Scholar]
  • 27.Vogler WR, Chan YK. Prolonging remission in myeloblastic leukemia by Tice-strain Bacillus Calmette-Guérin . Lancet. 1974;II:128. doi: 10.1016/S0140-6736(74)91556-6. [DOI] [PubMed] [Google Scholar]
  • 28.Whittaker JA, Bailey-Wood R, Hutchins S. Active immunotherapy for the treatment of acute myelogenous leukemia: the use of intravenous BCG and comparison between BCG and irradiated leukemic blast cells. In: Terry WD, Rosenberg SA, editors. Immunotherapy of cancer. New York: Ravan Press; 1982. p. 23. [Google Scholar]

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