Skip to main content
PMC home page
CMAJ : Canadian Medical Association Journal logoLink to CMAJ : Canadian Medical Association Journal
. 1989 Jan 15;140(2):137–142.

Clinical applications of recombinant human colony-stimulating factors.

H G Klingemann 1
PMCID: PMC1268583  PMID: 2642725

Abstract

The differentiation and maturation of hematopoietic progenitor cells are regulated by certain growth factors. Several of these glycoproteins have been characterized, and their amino acid sequences have been delineated. Modern DNA technology provides sufficient quantities of these hormones for testing in clinical trials. Erythropoietin (EPO) has been shown to increase the hemoglobin level and hematocrit in patients with end-stage renal disease. Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage CSF (GM-CSF) can increase the numbers of neutrophils and monocytes, in a dose-dependent fashion. The function of granulocytes and monocytes is also enhanced. Clinical studies of the toxicity and activity of G-CSF and GM-CSF have been conducted in patients with acquired immune deficiency syndrome, aplastic anemia, myelodysplastic syndromes, and neutropenia due to cancer and chemotherapy. In almost all patients the neutrophil count increased within 24 hours after the start of treatment. Side effects of G-CSF and GM-CSF are infrequent and usually mild. Combinations of CSFs may be even more effective.

Full text

PDF
137

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anasetti C., Doney K. C., Storb R., Meyers J. D., Farewell V. T., Buckner C. D., Appelbaum F. R., Sullivan K. M., Clift R. A., Deeg H. J. Marrow transplantation for severe aplastic anemia. Long-term outcome in fifty "untransfused" patients. Ann Intern Med. 1986 Apr;104(4):461–466. doi: 10.7326/0003-4819-104-4-461. [DOI] [PubMed] [Google Scholar]
  2. Antin J. H., Smith B. R., Holmes W., Rosenthal D. S. Phase I/II study of recombinant human granulocyte-macrophage colony-stimulating factor in aplastic anemia and myelodysplastic syndrome. Blood. 1988 Aug;72(2):705–713. [PubMed] [Google Scholar]
  3. Appelbaum F. R., Buckner C. D. Overview of the clinical relevance of autologous bone marrow transplantation. Clin Haematol. 1986 Feb;15(1):1–18. doi: 10.1016/s0308-2261(86)80003-0. [DOI] [PubMed] [Google Scholar]
  4. Appelbaum F. R., Storb R., Ramberg R. E., Shulman H. M., Buckner C. D., Clift R. A., Deeg H. J., Fefer A., Sanders J., Self S. Treatment of preleukemic syndromes with marrow transplantation. Blood. 1987 Jan;69(1):92–96. [PubMed] [Google Scholar]
  5. Armitage J. O., Jagannath S., Spitzer G., Bierman P., Kessinger A., Kumar P., Cabanillas F., Zander A., Vellekoop L., Dicke K. A. High dose therapy and autologous marrow transplantation as salvage treatment for patients with diffuse large cell lymphoma. Eur J Cancer Clin Oncol. 1986 Jul;22(7):871–877. doi: 10.1016/0277-5379(86)90376-7. [DOI] [PubMed] [Google Scholar]
  6. Baldwin G. C., Gasson J. C., Quan S. G., Fleischmann J., Weisbart R., Oette D., Mitsuyasu R. T., Golde D. W. Granulocyte-macrophage colony-stimulating factor enhances neutrophil function in acquired immunodeficiency syndrome patients. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2763–2766. doi: 10.1073/pnas.85.8.2763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Brandt S. J., Peters W. P., Atwater S. K., Kurtzberg J., Borowitz M. J., Jones R. B., Shpall E. J., Bast R. C., Jr, Gilbert C. J., Oette D. H. Effect of recombinant human granulocyte-macrophage colony-stimulating factor on hematopoietic reconstitution after high-dose chemotherapy and autologous bone marrow transplantation. N Engl J Med. 1988 Apr 7;318(14):869–876. doi: 10.1056/NEJM198804073181401. [DOI] [PubMed] [Google Scholar]
  8. Bronchud M. H., Scarffe J. H., Thatcher N., Crowther D., Souza L. M., Alton N. K., Testa N. G., Dexter T. M. Phase I/II study of recombinant human granulocyte colony-stimulating factor in patients receiving intensive chemotherapy for small cell lung cancer. Br J Cancer. 1987 Dec;56(6):809–813. doi: 10.1038/bjc.1987.295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Clark S. C., Kamen R. The human hematopoietic colony-stimulating factors. Science. 1987 Jun 5;236(4806):1229–1237. doi: 10.1126/science.3296190. [DOI] [PubMed] [Google Scholar]
  10. Doney K., Storb R., Buckner C. D., McGuffin R., Witherspoon R., Deeg H. J., Appelbaum F. R., Sullivan K. M., Thomas E. D. Treatment of aplastic anemia with antithymocyte globulin, high-dose corticosteroids, and androgens. Exp Hematol. 1987 Mar;15(3):239–242. [PubMed] [Google Scholar]
  11. Eschbach J. W., Egrie J. C., Downing M. R., Browne J. K., Adamson J. W. Correction of the anemia of end-stage renal disease with recombinant human erythropoietin. Results of a combined phase I and II clinical trial. N Engl J Med. 1987 Jan 8;316(2):73–78. doi: 10.1056/NEJM198701083160203. [DOI] [PubMed] [Google Scholar]
  12. Gerson S. L., Talbot G. H., Hurwitz S., Strom B. L., Lusk E. J., Cassileth P. A. Prolonged granulocytopenia: the major risk factor for invasive pulmonary aspergillosis in patients with acute leukemia. Ann Intern Med. 1984 Mar;100(3):345–351. doi: 10.7326/0003-4819-100-3-345. [DOI] [PubMed] [Google Scholar]
  13. Groopman J. E., Mitsuyasu R. T., DeLeo M. J., Oette D. H., Golde D. W. Effect of recombinant human granulocyte-macrophage colony-stimulating factor on myelopoiesis in the acquired immunodeficiency syndrome. N Engl J Med. 1987 Sep 3;317(10):593–598. doi: 10.1056/NEJM198709033171003. [DOI] [PubMed] [Google Scholar]
  14. Klingemann H. G., Eaves C. J. Colony stimulating factors. Bone Marrow Transplant. 1988 May;3(3):177–184. [PubMed] [Google Scholar]
  15. Morrissey P. J., Bressler L., Park L. S., Alpert A., Gillis S. Granulocyte-macrophage colony-stimulating factor augments the primary antibody response by enhancing the function of antigen-presenting cells. J Immunol. 1987 Aug 15;139(4):1113–1119. [PubMed] [Google Scholar]
  16. Munker M., Munker R., Saxton R. E., Koeffler H. P. Effect of recombinant monokines, lymphokines, and other agents on clonal proliferation of human lung cancer cell lines. Cancer Res. 1987 Aug 1;47(15):4081–4085. [PubMed] [Google Scholar]
  17. Nagata S., Tsuchiya M., Asano S., Kaziro Y., Yamazaki T., Yamamoto O., Hirata Y., Kubota N., Oheda M., Nomura H. Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor. 1986 Jan 30-Feb 5Nature. 319(6052):415–418. doi: 10.1038/319415a0. [DOI] [PubMed] [Google Scholar]
  18. Nemunaitis J., Singer J. W., Buckner C. D., Hill R., Storb R., Thomas E. D., Appelbaum F. R. Use of recombinant human granulocyte-macrophage colony-stimulating factor in autologous marrow transplantation for lymphoid malignancies. Blood. 1988 Aug;72(2):834–836. [PubMed] [Google Scholar]
  19. Nienhuis A. W., Donahue R. E., Karlsson S., Clark S. C., Agricola B., Antinoff N., Pierce J. E., Turner P., Anderson W. F., Nathan D. G. Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) shortens the period of neutropenia after autologous bone marrow transplantation in a primate model. J Clin Invest. 1987 Aug;80(2):573–577. doi: 10.1172/JCI113106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pizzo P. A. Granulocytopenia and cancer therapy. Past problems, current solutions, future challenges. Cancer. 1984 Dec 1;54(11 Suppl):2649–2661. doi: 10.1002/1097-0142(19841201)54:2+<2649::aid-cncr2820541409>3.0.co;2-6. [DOI] [PubMed] [Google Scholar]
  21. Souza L. M., Boone T. C., Gabrilove J., Lai P. H., Zsebo K. M., Murdock D. C., Chazin V. R., Bruszewski J., Lu H., Chen K. K. Recombinant human granulocyte colony-stimulating factor: effects on normal and leukemic myeloid cells. Science. 1986 Apr 4;232(4746):61–65. doi: 10.1126/science.2420009. [DOI] [PubMed] [Google Scholar]
  22. Tomonaga M., Golde D. W., Gasson J. C. Biosynthetic (recombinant) human granulocyte-macrophage colony-stimulating factor: effect on normal bone marrow and leukemia cell lines. Blood. 1986 Jan;67(1):31–36. [PubMed] [Google Scholar]
  23. Varela B. L., Chuang C., Woll J. E., Bennett J. M. Modifications in the classification of primary myelodysplastic syndromes: the addition of a scoring system. Hematol Oncol. 1985 Jan-Mar;3(1):55–63. doi: 10.1002/hon.2900030108. [DOI] [PubMed] [Google Scholar]
  24. Weisbart R. H., Golde D. W., Clark S. C., Wong G. G., Gasson J. C. Human granulocyte-macrophage colony-stimulating factor is a neutrophil activator. 1985 Mar 28-Apr 3Nature. 314(6009):361–363. doi: 10.1038/314361a0. [DOI] [PubMed] [Google Scholar]
  25. Wong G. G., Temple P. A., Leary A. C., Witek-Giannotti J. S., Yang Y. C., Ciarletta A. B., Chung M., Murtha P., Kriz R., Kaufman R. J. Human CSF-1: molecular cloning and expression of 4-kb cDNA encoding the human urinary protein. Science. 1987 Mar 20;235(4795):1504–1508. doi: 10.1126/science.3493529. [DOI] [PubMed] [Google Scholar]
  26. Wong G. G., Witek J. S., Temple P. A., Wilkens K. M., Leary A. C., Luxenberg D. P., Jones S. S., Brown E. L., Kay R. M., Orr E. C. Human GM-CSF: molecular cloning of the complementary DNA and purification of the natural and recombinant proteins. Science. 1985 May 17;228(4701):810–815. doi: 10.1126/science.3923623. [DOI] [PubMed] [Google Scholar]
  27. Yang Y. C., Ciarletta A. B., Temple P. A., Chung M. P., Kovacic S., Witek-Giannotti J. S., Leary A. C., Kriz R., Donahue R. E., Wong G. G. Human IL-3 (multi-CSF): identification by expression cloning of a novel hematopoietic growth factor related to murine IL-3. Cell. 1986 Oct 10;47(1):3–10. doi: 10.1016/0092-8674(86)90360-0. [DOI] [PubMed] [Google Scholar]

Articles from CMAJ: Canadian Medical Association Journal are provided here courtesy of Canadian Medical Association

RESOURCES