Granulocyte colony-stimulating factor: biology and clinical potential

  • Maryann Foote
  • Bertrand C. Liang
  • Jeffrey Crawford
  • Frankie A. Holmes
  • Michael Green
  • Frankie A. Holmes
  • Michael Green
  • George Morstyn


The study of hematopoiesis was greatly facilitated in the mid-1960s when techniques for studying hematopoietic cells in clonal culture were developed. Initially, serum or conditioned medium was added to cultures as a source of growth factors, the colony-stimulating factors (CSFs) [58]. One of the factors that was isolated, purified, cloned, and produced in commercial quantities was granulocyte-colony stimulating factor (G-CSF), a protein that acts on the neutrophil lineage to selectively stimulate the proliferation and differentiation of committed progenitor cells and activation of mature neutrophils (Fig. 1). A property that distinguished G-CSF from other CSFs and facilitated its purification, molecular cloning, and large-scale production in prokaryotic cells was its ability to induce terminal differentiation of a murine leukemic cell line (WEHI-3B). After observing that serum from endotoxin-treated mice was capable of causing the differentiation of a WEHI-3B myelomonocytic leukemic cell line, Metcalf [57] named the activity GM—DF (granulocyte-macrophage differentiating factor). Further analysis showed that this serum contained G—CSF as well as granulocyte-macrophage colony-stimulating factor (GM-CSF). Nicola et al. [70] further purified GCSF from medium conditioned by lung tissue of endotoxin-treated mice. This G-CSF could stimulate WEHI-3B cells as well as normal cells, supporting the formation of numerous small, neutrophil-containing colonies at a concentration similar to that needed for WEHI-3B differentiation [69]. Subsequently, murine G-CSF was identified as a protein and was shown to have both differentiation-inducing activity for WEHI-3B as well as granulocyte colony-stimulating activity in bone-marrow cells [70]. Other researchers, notably Asano et al. [4] and Welte et al. [105], found several human carcinoma cells that constitutively produce colony-stimulating factors. One of these factors was purified to apparent homogeneity from the conditioned medium of bladder carcinoma 5637 cells [105] or a squamous carcinoma cell line [73]. The purified CSF selectively stimulated neutrophilic granulocyte-colony formation from bone-marrow cells, so it was concluded that this factor was the human counterpart to mouse G-CSF. The protein initially identified as G-CSF was also called CSF-13 and Pluripoietin (pCSF).


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Abboud MR, Layer J, Blau CA. Elevation of neutrophil counts after G-CSF administration leads to vaso-occlusive crisis and acute chest syndrome in a patient with sickle cell anemia. Blood 1996; 88: 15b (abstract).Google Scholar
  2. 2.
    Anyaegbu CC, Pkpala IE, Aken’Ova YA, Salimonu LS. Peripheral blood neutrophil counts and candidacidal activity correlated with the clinical severity of sickle cell anemia. Eur J Haematol 1998; 60: 267–8.PubMedGoogle Scholar
  3. 3.
    Asano S. Human granulocyte colony-stimulating factor: its basic aspects and clinical applications. Am J Ped HematolI Oncol 1991; 13: 400–13.Google Scholar
  4. 4.
    Asano S, Sato N, Mori M et al. Detection and assessment of human granulocyte-macrophage colony-stimulating factor (GM-CSF) producing tumours by heterotransplantation into nude mice. Br J Cancer 1980; 41: 689–94.PubMedCentralPubMedGoogle Scholar
  5. 5.
    Azuma J, Kurimoto T, Awata S et al. Phase I study of KRN8601 (rhG-CSF) in normal healthy volunteers: safety and pharmacokinetics in single s.c. administration. Rinsho Iyaka 1989; 5: 2231–52.Google Scholar
  6. 6.
    Bacigalupo A, Hows J, Gluckman E et al. Bone marrow transplantation (BMT) versus immunosuppression for treatment of severe aplastic anemia (SAA): a report of the EBMT SAA Working Party. Br J Haematol 1988; 70: 177–82.PubMedGoogle Scholar
  7. 7.
    Bessho M, Toyoda A, Itoh N et al. Trilineage recovery by combination therapy with recombinant human granulocyte colony-stimulating factor (rhGCSF) and erythropoietin (rhEPO) in severe aplastic anemia. Br J Haematol 1992; 80: 409–11.PubMedGoogle Scholar
  8. 8.
    Bodey GP, Buckley M, Sathe YS, Freierich EJ. Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia. Ann Intern Med 1966; 64: 328–40.PubMedGoogle Scholar
  9. 9.
    Bronchud MH, Howell A, Crother D et al. Phase IIII study of recombinant human granulocyte colony-stimulating factor to increase the intensity of treatment with doxorubicin in patients with advanced breast and ovarian cancer. Br J Cancer 1989; 60: 121–8.PubMedCentralPubMedGoogle Scholar
  10. 10.
    Bronchud MH, Potter MR, Morgenstern C et al. In vitro and in vivo analysis of the effects of recombinant human granulocyte colony-stimulating factor in patients. Br J Cancer 1988; 58: 64–9.PubMedCentralPubMedGoogle Scholar
  11. 11.
    Bronchud MH, Scarffe JH, Thatcher N et al. Phase IIII study of recombinant human granulocyte colony-stimulating factor in patients receiving intensive chemotherapy for small cell lung cancer. Br J Cancer 1987; 56: 809–13.PubMedCentralPubMedGoogle Scholar
  12. 12.
    Cebon JS, Layton JE, Maher D, Morstyn G. Endogenous haemopoietic growth factors in neutropenia and infection. Br J Haematol 1994; 86: 263–74.Google Scholar
  13. 13.
    Chao NJ, Schriber JR, Grimes K et al. Granulocyte colony-stimulating factor ‘mobilized’ peripheral blood progenitor cells accelerate granulocyte and platelet recovery after high-dose chemotherapy. Blood 1993; 81: 2031–5.PubMedGoogle Scholar
  14. 14.
    Chevallier B, Chollet P, Merrouche Y et al. Lenograstim prevents morbidity from intensive induction chemotherapy in the treatment of inflammatory breast cancer. J Clin Oncol 1995; 13: 1564–71.PubMedGoogle Scholar
  15. 15.
    Chugai Pharma. UK Ltd. ABPI Compendium of Data Sheets and Summaries of Product Characteristics. London: Datapharm Publications, 1999.Google Scholar
  16. 16.
    Colgan SP, Gasper PW, Thrall, MA, Boone TC, Blancquaert AMB, Bruyninckx WJ. Neutrophil function in normal and Chediak-Higashi syndrome cats following administration of recombinant canine granulocyte colony-stimulating factor. Exp Hematol 1992; 20: 1229–34.PubMedGoogle Scholar
  17. 17.
    Crawford J, Kreisman H, Garewal H et al. A pharmacodynamic investigation of recombinant human granulocyte colony stimulating factor r-metHuG-SCF) schedule variation in patients with small cell lung cancer (SCLC) given CAE chemotherapy. J Clin Oncol 1992; 11: 299 (abstract).Google Scholar
  18. 18.
    Crawford J, Ozer H, Stoller R et al. Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer. N Eng J Med 1991; 325: 164–70.Google Scholar
  19. 19.
    Dale DC, Fier C, Welte K. Use of filgrastim (r-metHuGCSF) in severe chronic neutropenia. In: Morstyn G, Dexter TM, Foote MA, eds. Filgrastim (r-metHuG-CSF) in Clinical Practice. New York: Marcel Dekker Inc., 1998: 121–47.Google Scholar
  20. 20.
    Dale DC, Bonilla MA, Davis MS et al. A randomized controlled phase III trial of recombinant human granulocyte colony-stimulating factor (Filgrastim) for treatment of severe chronic neutropenia. Blood 1993; 81: 2496–502.PubMedGoogle Scholar
  21. 21.
    Demetri GD, Griffin JD. Granulocyte colony-stimulating factor and its receptor. Blood 1991; 78: 2791–808.PubMedGoogle Scholar
  22. 22.
    Devlin JJ, Devlin PE, Myamabo K et al. Expression of granulocyte colony-stimulating factor by human cell lines. J Leukocyte Biol 1987; 41: 302–6.PubMedGoogle Scholar
  23. 23.
    Donadieu J, Boutard P, Bernatowski E et al. A European phase II study of recombinant human granulocyte colony-stimulating factor (lenograstim) in the treatment of severe chronic neutropenia in children. Eur J Pediatr 1997; 156: 693–700.PubMedGoogle Scholar
  24. 24.
    Dunn CJ, Goa KL. Lenograstim. An update of its pharmacological properties and use in chemotherapy-induced neutropenia and related clinical settings. Drugs 2000; 59: 681–717.PubMedGoogle Scholar
  25. 25.
    Dürhsen U, Villeval JL, Boyd J, Kannourakis G, Morstyn G, Metcalf D. Effects of recombinant human granulocyte colony-stimulating factor on hematopoietic progenitor cells in cancer patients. Blood 1988; 72: 2074–81.Google Scholar
  26. 26.
    Eliason JF, Greway A, Tare N et al. Extended activity in cynomolgus monkeys of a granulocyte colony-stimulating factor mutein conjugated with high molecular weight polyethylene glycol. Stem Cells 2000; 18: 40–5.PubMedGoogle Scholar
  27. 27.
    Ernst TJ, Ritchie AR, Demetri GD et al. Regulation of granulocyte colony-stimulating factor mRNA levels in human blood monocytes is mediated primarily at the posttranscriptional level. J Biol Chem 1989; 264: 5700–3Google Scholar
  28. 28.
    Frampton JE, Lee CR, Faulds D. Filgrastim. A review of its pharmacological properties and therapeutic efficacy in neutropenia. Drug Eval 1995; 48: 731–60.Google Scholar
  29. 29.
    Gabrilove JL, Jakubowski A, Fain K et al. Phase I study of granulocyte colony-stimulating factor in patients with transitional cell carcinoma of the urothelium. J Clin Invest 1988; 82: 1454–61.PubMedCentralPubMedGoogle Scholar
  30. 30.
    Gabrilove JL, Jakubowski A, Scher H et al. Effect of granulocyte colony-stimulating factor on neutropenia and associated morbidity due to chemotherapy for transitional-cell carcinoma of the urothelium. N Engl J Med 1988; 318: 1414–422.PubMedGoogle Scholar
  31. 31.
    George S, Yunus F, Case D et al. Fixed-dose pegfilgrastim is safe and allows neutrophil recovery in patients with non-Hodgkin’s lymphoma, Leuk Lymphoma (in press).Google Scholar
  32. 32.
    Gisselbrecht C, Haioun B, Lepage E et al. Placebo-controlled phase III study of lenograstim (glycosylated recombinant human granulocyte colony-stimulating factor) in aggressive non-Hodgkin’s lymphoma: factors influencing chemotherapy administration. Leuk Lymphoma 1997; 25: 289–300.PubMedGoogle Scholar
  33. 33.
    Gisselbrecht C, Prentice HG, Bacigalupo A et al. Placebo-controlled phase III trial of lenograstim in bone-marrow transplantation. Lancet 1994; 343: 696–700.PubMedGoogle Scholar
  34. 34.
    Gluckman E, Rokicka-Milewska R, Gordon-Smith EC et al. Results of a randomized study of glycosylated rHuG-CSF lenograstim in severe aplastic anemia. Blood 1998; 92: 376A (abstract).Google Scholar
  35. 35.
    Green M, Koelbl H, Baselga J et al. A randomized, double-blind multicenter phase III study of fixed-dose single administration pegfilgrastim versus daily filgrastim in patients receiving myelosuppressive chemotherapy. Ann Oncol 2003; 14: 29–35.PubMedGoogle Scholar
  36. 36.
    Häkansson L, Hoglund M, Jonsson UB et al. Effects of in vivo administration of G-CSF on neutrophil and eosinophil adhesion. Br J Haematol 1997; 98: 603–11.PubMedGoogle Scholar
  37. 37.
    Hoglund M. Glycosylated and non-glycosylated recombinant human granulocyte colony-stimulating factor (rhGCSF)–what is the difference? Med Oncol 1998; 15: 229–33.PubMedGoogle Scholar
  38. 38.
    Hoglund M, Häkansson L, Venge P. Effects of in vivo administration of G-CSF on neutrophil functions in healthy volunteers. Eur J Haematol 1997; 58: 195–202.PubMedGoogle Scholar
  39. 39.
    Holmes FA, O’Shaughnessy JA, Vukelja S et al. Blinded, randomized, multicenter study to evaluate single administration pegfilgrastim once per cycle versus daily filgrastim as an adjunct to chemotherapy in patients with high-risk stage II or stage IIIIIV breast cancer. J Clin Oncol 2002; 20: 727–31.PubMedGoogle Scholar
  40. 40.
    Houston AC, Stevens LA, Cour V. Pharmacokinetics of glycosylated recombinant human granulocyte colony-stimulating factor (lenograstim) in healthy male volunteers. Br J Haematol 1999; 47: 279–84.Google Scholar
  41. 41.
    Johnston E, Crawford J, Blackwell S et al. Randomized, dose-escalation study of SDI 01 compared with daily filgrastim in patients receiving chemotherapy. J Clin Oncol 2000; 18: 2522–8.PubMedGoogle Scholar
  42. 42.
    Kawakami M, Tsutsumi H, Kumakawa I et al. Levels of serum granulocyte colony-stimulating factor in patients with infections. Blood 1990; 76: 1962–4.PubMedGoogle Scholar
  43. 43.
    Kawano Y, Takaue Y, Watanabe T et al. Effects of progenitor cell dose and preleukapheresis use of human recombinant granulocyte colony-stimulating factor on the recovery of hematopoiesis after blood stem cell auto-grafting in children. Exp Hematol 1993; 21: 103–8.PubMedGoogle Scholar
  44. 44.
    Kojima S, Fukuda M, Miyajima Y, Matsuyama T, Horibe K. Treatment of aplastic anemia in children with recombinant human granulocyte colony-stimulating factor. Blood 1991; 77: 937–41.PubMedGoogle Scholar
  45. 45.
    Kuga T, Komatsu Y, Yamaski M et al. Mutagenesis of human granulocyte colony stimulating factor. Biochem Biophys Res Commun 1989; 159: 103–11.PubMedGoogle Scholar
  46. 46.
    Kuritzkes DR, Parenti D, Ward D et al. Filgrastim prevents severe neutropenia and reduces infective morbidity in patients with advanced HIV infection: results of a randomized, multicenter, controlled trial. AIDS 1998; 12: 65–74.PubMedGoogle Scholar
  47. 47.
    Layton JE, Hockman H, Sheridan WP, Morstyn G. Evidence for a novel in vivo control mechanism of granulopoiesis: mature cell-related control of regulatory growth factor. Blood 1989; 74: 1303–7.PubMedGoogle Scholar
  48. 48.
    Lefrere F, Bernard M, Audat F et al. Comparison of lenograstim vs filgrastim administration following chemotherapy for peripheral blood stem cell (PBSC) collection: a retrospective study of 126 patients. Leuk Lymphoma 1999; 35: 501–5.PubMedGoogle Scholar
  49. 49.
    Lieschke GJ, Grail D, Hodgson G et al. Mice lacking granulocyte colony-stimulating factor have chronic neutropenia, granulocyte and macrophage progenitor cell deficiency, and impaired neutrophil mobilization. Blood 1994; 84: 1737–46.PubMedGoogle Scholar
  50. 50.
    Lieschke GJ, Burgess AW. Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor (1). N Engl J Med 1992; 327: 28–35.PubMedGoogle Scholar
  51. 51.
    Lieschke GJ, Burgess AW. Granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor (2). N Engl J Med 1992; 327: 99–106.PubMedGoogle Scholar
  52. 52.
    Lieschke GJ, Cebon J, Morstyn G. Characterization of the clinical effects after the first dose of bacterially synthesized recombinant human granulocyte-macrophage colony-stimulating factor. Blood 1989; 74A: 2634–43.PubMedGoogle Scholar
  53. 53.
    Linch DC, Scarrffe H, Proctor S et al. Randomised vehicle-controlled dose finding study of glycosylated recombinant human granulocyte colony-stimulating factor after bone marrow transplantation. Bone Marrow Transplant 1993; 11: 307–11.PubMedGoogle Scholar
  54. 54.
    Lindemann A, Herrmann F, Oster W, et aI. Hematologic effects of recombinant human granulocyte colony-stimulating factor in patients with malignancy. Blood 1989; 74: 2644–51.PubMedGoogle Scholar
  55. 55.
    Lord BI, Gurney H, Chang J et al. Haemopoietic cell kinetics in humans treated with rGM-CSF. Int J Cancer 1992; 50: 26–31.PubMedGoogle Scholar
  56. 56.
    Lord Bl, Bronchud MH, Owens S et al. The kinetics of human granulopoiesis following treatment with granulocyte colony-stimulating factor. Proc Natl Acad Sci USA 1989; 86: 9499–503.Google Scholar
  57. 57.
    Metcalf D. Clonal extinction of myelomonocytic leukaemia cells by serum from mice infected with endotoxin. Int J Cancer 1980; 25: 225–33.PubMedGoogle Scholar
  58. 58.
    Metcalf D. The Molecular Control of Blood Cells. Cambridge, MA: Harvard University Press, 1988.Google Scholar
  59. 59.
    Metcalf D, Morstyn G. Colony stimulating factors: general biology. In: De Vita V, ed. Biologic Therapy of Cancer. Philadelphia: JB Lippincott, 1991: 417–44.Google Scholar
  60. 60.
    Molineux G, Kinstler O, Briddell B et al. A new form of filgrastim with sustained duration in vivo and enhanced ability to mobilize PBPC in both mice and humans. Exp Hematol 1999; 27: 1724–34.PubMedGoogle Scholar
  61. 61.
    Morstyn G, Dexter TM, Foote MA, eds. Filgrastim (rmetHuG-CSF) in Clinical Practice. New York: Marcel Dekker Inc., 1998.Google Scholar
  62. 62.
    Morstyn G, Campbell L, Lieschke G et al. Treatment of chemotherapy-induced neutropenia by s.c. administered granulocyte colony-stimulating factor with optimization of dose and duration of therapy. Clin Oncol 1989a; 7: 1554–62.Google Scholar
  63. 63.
    Morstyn G, Lieschke GJ, Cebon J et al. Early clinical trials with colony-stimulating factors. Cancer Invest 1989b; 7: 443–56.PubMedGoogle Scholar
  64. 64.
    Morstyn G, Burgess AW. Hemopoietic growth factors: a review. Cancer Res 1988; 48: 5624–37.PubMedGoogle Scholar
  65. 65.
    Morstyn G, Campbell L, Souza LM et al. Effect of granulocyte colony-stimulating factor on neutropenia induced by cytotoxic chemotherapy. Lancet 1988; 1: 667–72.PubMedGoogle Scholar
  66. 66.
    Nagata S, Tsuchiya M, Asano S et al. Molecular cloning and expression of cDNA for human granulocyte colony stimulating factor. Nature 1986; 319: 415–18.PubMedGoogle Scholar
  67. 67.
    Negrin RS, Greenberg PL. Filgrastim (r-metHuG-CSF) for the treatment of myelodysplastic syndromes. In: Morstyn G, Dexter TM, Foote MA, eds. Filgrastim (r-metHuG-CSF) in Clinical Practice. New York: Marcel Dekker Inc., 1998: 491–510.Google Scholar
  68. 68.
    Nicola NA, Metcalf D. Differential induction in leukemic cells by normal growth factor regulators: molecular and binding properties of purified granulocyte colony-stimulating factor. In: Bishop JM, Rowley JD, Greaves M, eds. Genes and Cancer. New York, NY: Alan R Less, 1984: 591–610.Google Scholar
  69. 69.
    Nicola NA. Hemopoietic cell growth factors and their receptors. Ann Rev Biochem 1989; 58: 45–77.PubMedGoogle Scholar
  70. 70.
    Nicola NA, Metcalf D, Matsumoto M, Johnson CR. Purification of a factor inducing differentiation in murine myelomonocytic leukaemia cells: identification as granulocyte colony-stimulating factor (G-CSF). J Biol Chem 1983; 258: 9017–23.PubMedGoogle Scholar
  71. 71.
    Nicola NA, Metcalf D. Biochemical properties of differentiation factors for murine myelomonocytic leukemic cells in organ-conditioned media. Separation from colony stimulating factors. J Cell Physiol 1981; 109: 253–64.PubMedGoogle Scholar
  72. 72.
    Nio Y, Siriasis I, Stubborn M et al. Comparative effects of a recombinant and a mutein type of granulocyte colony stimulating factor on the growth of fibrosarcoma with 5- fluorouracil chemotherapy. Biotherapy 1992; 4: 81–6.PubMedGoogle Scholar
  73. 73.
    Nomura H, Imazeki I, Oheda M et al. Purification and characterization of human granulocyte colony stimulating factor (C-CSF). EMBO J 1986; 5: 871–6.Google Scholar
  74. 74.
    O’Callahan P, Smartt P, Smith R et al. Peripheral blood progenitor cell (PBPC) mobilization with cyclophosphamide and single vial dose (263MGC) lenograstim (G-CSF) in patients with malignant lymphoma receiving BEAM chemotherapy with PBPC transplantation. Bone Marrow Transplant 1997; 19: S108 (abstract).Google Scholar
  75. 75.
    Oheda M, Hasegawa M, Hatton K et al. O-linked sugar chain of human granulocyte colony-stimulating factor protects it against polymerization and denaturation allowing it to retain its biological activity. Biol Chem 1990; 265: 11482–85.Google Scholar
  76. 76.
    Oheda M, Hase S, Ono M, Ikenaka T. Structure of the sugar chains of recombinant human granulocyte colony-stimulating factor produced by Chinese hamster ovary cells. J Biochem 1988; 103: 544–6.PubMedGoogle Scholar
  77. 77.
    Osslund T, Boone T. Biochemistry and structure of filgrastim (r-metHuG-CSF). In: Morstyn G, Dexter TM, Foote MA, eds. Filgrastim (r-metHuG-CSF) in Clinical Practice. New York: Marcel Dekker, Inc., 1998: 41–9.Google Scholar
  78. 78.
    Panagapoulos J, Petrogiannopoulos C, Zaharof A et al. The effect of lenograstim (G-CSF) in patients with infection and myelodysplastic syndrome. Br J Haematol 1996; 93: 276 (abstract).Google Scholar
  79. 79.
    Platt OS, Brambilla DJ, Rosse WF et al. Mortality in sickle cell disease–life expectancy and risk factors for early death. N Engl J Med 1994; 330: 1639–44.PubMedGoogle Scholar
  80. 80.
    Platzer E. Human hemopoietic growth factors. Eur J Haematol 1989; 42: 1–15.PubMedGoogle Scholar
  81. 81.
    Raghavachar A, Schrezenmeier H, Bacigalupo A. Use of filgrastim (r-metHuG-CSF) in aplastic anemia. In: Morstyn G, Dexter TM, Foote MA, eds. Filgrastim (r-metHuG-CSF) in Clinical Practice. New York: Marcel Dekker Inc., 1998: 533–51.Google Scholar
  82. 82.
    Rapoport AP, Abboud CN, Di Persio JF. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF): receptor biology, signal transduction, and neutrophil activation. Blood Rev 1992; 6: 43–57.PubMedGoogle Scholar
  83. 83.
    Rennick D, Yang G, Gemmell L et al.. Control of hemopoiesis by a bone marrow stroma cell clone: lipopolysaccharide-and interleukin-1-inducible production of colony-stimulating factors. Blood 1987; 69: 682–691.PubMedGoogle Scholar
  84. 84.
    Roskos LK, Cheung EN, Vincent M, Foote MA, Morstyn G. Pharmacology of filgrastim (r-metHuG-CSF). In: Morstyn G, Dexter TM, Foote MA, eds. Filgrastim (r-metHuGCSF) in Clinical Practice. New York: Marcel Dekker Inc., 1998: 51–71.Google Scholar
  85. 85.
    Sekino H, Moriya K, Sugano I, Wakabayashi K, Okazaki A. Recombinant human G-CSF (rG-CSF). Shinryo Shinyaku 1989; 26: 32–104.Google Scholar
  86. 86.
    Sheridan WP, Begley CG, Juttner CA et al. Effect of peripheral-blood progenitor cells mobilised by filgrastim (G-CSF) on platelet recovery after high-dose chemotherapy. Lancet 1992; 339: 640–4.PubMedGoogle Scholar
  87. 87.
    Sheridan WP, Juttner C, Szer J et al. Granulocyte colony-stimulating factor (G-CSF) in peripheral blood stem cell (PBSC) and bone marrow transplantation. Blood 1990; 76: SI.Google Scholar
  88. 88.
    Simmers RN, Webber LM, Shannon MF et al. Location of the G-CSF gene on chromosome 17 proximal to the breakpoint in the T(15;17) in acute promyelocytic leukemia. Blood 1987; 70: 330–2.PubMedGoogle Scholar
  89. 89.
    Souza LM, Boone TC, Gabrilove J et al. Recombinant human granulocyte colony-stimulating factor: effects on normal and leukemic myeloid cells. Science 1986; 232: 61–5.PubMedGoogle Scholar
  90. 90.
    Stahel RA, Jost LM, Cerny T et al. Randomized study of recombinant granulocyte colony-stimulating factor after high-dose chemotherapy and autologous bone marrow transplantation for high-risk lymphoid malignancies. J Clin Oncol 1994; 12: 1931–8.PubMedGoogle Scholar
  91. 91.
    Steward WP. Granulocyte and granulocyte-macrophage colony-stimulating factors. Lancet 1993; 342: 153–7.PubMedGoogle Scholar
  92. 92.
    Suzuki K, Tsunoo M, Shishido A, Kuwabara T, Kobayashi S. Phase I study of KW-2288 in normal healthy volunteers. J Clin Ther Med 1991; 7: 1947–71.Google Scholar
  93. 93.
    Takeshita A, Saito H, Toyama K et al. Efficacy of a new formulation of lenograstim (recombinant glycosylated human granulocyte colony-stimulating factor) containing gelatin for the treatment of neutropenia after consolidation chemotherapy in patients with acute myeloid leukemia. Int J Hematol 2000; 71: 136–43.PubMedGoogle Scholar
  94. 94.
    Tanaka H, Kaneko T. Pharmacokinetic and pharmacodynamic comparisons between human granulocyte colony-stimulating factor purified from human bladder carcinoma cell line 5637 culture medium and recombinant human granulocyte colony-stimulating factor produced in Escherichia coli. J Pharm Exp Ther 1992; 262: 439–44.Google Scholar
  95. 95.
    Trillet-Lenoir V, Green J, Manegold C et al. Recombinant granulocyte colony stimulating factor reduces the infectious complications of cytotoxic chemotherapy. Eur J Cancer 1993; 29A: 319–24.Google Scholar
  96. 96.
    Turzanski J, Crouch SP, Fletcher J, Hunter A. Ex vivo neutrophil function in response to three different doses of glycosylated rHuG-CSF (Lenograstim). Br J Haematol 1997; 96: 46–54.PubMedGoogle Scholar
  97. 97.
    van der Auwera P, Platzer E, Xu ZX et al. Pharmacodynamics and pharmacokinetics of single doses of s.c. pegylated human G-CSF mutant (Ro 25–8315) in healthy volunteers: comparison with single and multiple daily doses of filgrastim. Am J Hematol 2001; 66: 245–51.Google Scholar
  98. 98.
    Van der Wouw PA, van Leeuwen R, van Oers RH et al. Effects of recombinant human granulocyte colony-stimulating factor on leucopenia in zidovudine-treated patients with AIDS and AIDS-related complex, a phase IIII study. Br J Haematol 1991; 78: 319–24.PubMedGoogle Scholar
  99. 99.
    Vellenga E, Rambaldi A, Ernst TI, Ostapovicz D, Griffin JD. Independent regulation of M-CSF and C-CSF gene expression in human monocytes. Blood 1988; 71: 1529–32.PubMedGoogle Scholar
  100. 100.
    Walker BD. Immune reconstitution: is there a potential role for filgrastim (r-metHuG-CSF)? J Hematother Stem Cell Res 1999; 8: S1–2.PubMedGoogle Scholar
  101. 101.
    Watari K, Asano S, Shirafuji N et al. Serum granulocyte colony-stimulating factor levels in healthy volunteers and patients with various disorders as estimated by enzyme immunoassay. Blood 1989; 73: 117–22.PubMedGoogle Scholar
  102. 102.
    Watts MI, Sullivan AM, Jamieson E et al. Progenitor-cell mobilization after low-dose cyclophosphamide and granulocyte colony-stimulating factor: an analysis of progenitor-cell quantity and quality and factors predicting for these parameters in 101 pretreated patients with malignant lymphoma. J Clin Oncol 1997; 15: 535–46.PubMedGoogle Scholar
  103. 103.
    Weisbart RH, GoIde DW. Physiology of granulocyte and macrophage colony-stimulating factors in host defense. Hematol Oncol Clin N Am 1989; 3: 401–9.Google Scholar
  104. 104.
    Welte K, Gabrilove J, Bronchud MH, Platzer E, Morstyn G. Filgrastim (r-metHuG-CSF): the first 10 years. Blood 1996; 86: 1907–29.Google Scholar
  105. 105.
    Welte K, Platzer E, Lu L et al. Purification and biochemical characterization of human pluripotent hematopoietic colony-stimulating factor. Proc Natl Acad Sci USA 1985; 82: 1526–30.PubMedGoogle Scholar
  106. 106.
    World Health Organization (WHO). International collaborative study for the proposed international standards for granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor. WHO Technical Report Series, 1994.Google Scholar
  107. 107.
    Yamamoto Y, Klein TW, Friedman H, Kimura S, Yamaguchi H. Granulocyte colony-stimulating factor potentiates anti-Candida albicans growth inhibitory activity of polymorphonuclear cells. FEM Immunol Med Microbiol 1993; 7: 15–22.Google Scholar
  108. 108.
    Yoshida Y, Hirashima K, Asano S et al. A phase II trial of recombinant human granulocyte colony-stimulating factor in the myelodysplastic syndromes. Br J Haematol 1991; 78: 378–84.PubMedGoogle Scholar
  109. 109.
    Zsebo KM, Cohen AM, Murdock DC et al. Recombinant human granulocyte colony-stimulating factor: molecular and biological characterization. Immunobiology 1986; 172: 175–84.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2003

Authors and Affiliations

  • Maryann Foote
  • Bertrand C. Liang
  • Jeffrey Crawford
  • Frankie A. Holmes
  • Michael Green
  • Frankie A. Holmes
  • Michael Green
  • George Morstyn

There are no affiliations available

Personalised recommendations