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Haematopoietic Growth Factors

Glycosylated vs non-glycosylated granulocyte colony-stimulating factor (G-CSF) – results of a prospective randomised monocentre study

Bone Marrow Transplantation volume 28, pages 259–264 (2001)Cite this article

Abstract

The discovery of the haematopoietic growth factor granulocyte colony-stimulating factor (G-CSF) has reduced infection-related morbidity in cancer patients by alleviating post-chemotherapy neutropenia. Two formulations of recombinant human (rh) G-CSF, one glycosylated and one non-glycosylated, are available. The glycosylated form, lenograstim, possesses at least 25% greater bioactivity in vitro. Some comparative studies into the preparation's potential to mobilise haematopoietic stem cells suggest a similar advantage. In the light of the great clinical importance of G-CSF, we have performed the first prospective, randomised, crossover study on children with chemotherapy-induced neutropenia. G-CSF (250 μg/m2) was started 1 day after the chemotherapy block, and was administered until a WBC >1500/μl was achieved on 3 successive days. Thirty-three G-CSF cycles from 11 patients (16 lenograstim, 17 filgrastim) were studied. They were investigated for duration of very severe (WBC <500/μl, 9 vs 9.5 days, lenograstim vsfilgrastim, median) and severe leukopenia (WBC <1000/μl, 11 vs 11 days), infections (CRP >5 mg/dl, 5 vs 5.5 days), infection-related hospital stay (11 vs 9 days) and antibiotic treatment (9 vs 9 days). Statistical evaluation by paired analysis could not detect any difference between treatment groups; the median difference for all end-points was zero. In summary, at least at 250 μg/m2, in terms of their clinical effect on neutropenia, the two G-CSF preparations appear to have identical activity. Bone Marrow Transplantation (2001) 28, 259–264.

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References

  1. Bronchud MH, Potter MR, Morgenstern G 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: 64–69

    Article  CAS  Google Scholar 

  2. Lord BI, Bronchud MH, Owens S et al. The kinetics of human granulopoiesis following treatment with granulocyte colony-stimulating factor in vivo Proc Natl Acad Sci USA 1989 86: 9499–9503

    Article  CAS  Google Scholar 

  3. Yamamoto Y, Klein TW, Friedman H et al. Granulocyte colony-stimulating factor potentiates anti-Candida albicans growth inhibitory activity of polymorphonuclear cells FEMS Immunol Med Microbiol 1993 7: 15–22

    Article  CAS  Google Scholar 

  4. 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 New Engl J Med 1991 325: 164–170

    Article  CAS  Google Scholar 

  5. 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: 319–324

    Article  CAS  Google Scholar 

  6. Welte K, Reiter A, Mempel K et al. A randomized phase-III study of the efficacy of granulocyte-colony stimulating factor in children with high-risk acute lymphoblastic leukemia Blood 1996 87: 3143–3150

    CAS  PubMed  Google Scholar 

  7. Schwinger W, Mache C, Urban C et al. Single dose of filgrastim (rhG-CSF) increases the number of hemopoietic progenitors in the peripheral blood of adult volunteers Bone Marrow Transplant 1993 22: 489–492

    Google Scholar 

  8. Sato N, Sawada K, Takahashi TA et al. A time course study for optimal harvest of peripheral blood progenitor cells by granulocyte colony-stimulating factor in healthy volunteers Exp Hematol 1994 22: 973–978

    CAS  Google Scholar 

  9. Duhrsen U, Villeval JL, Boyd J et al. Effects of recombinant human granulocyte colony-stimulating factor on hematopoietic progenitor cells in cancer patients Blood 1988 72: 2074–2081

    CAS  Google Scholar 

  10. De Luca, Sheridan WP, Watson D et al. Prior chemotherapy does not prevent effective mobilisation by G-CSF of peripheral blood progenitor cells Br J Cancer 1992 66: 893–899

    Article  Google Scholar 

  11. Welte K, Gabrilove J, Bronchud MH et al. Filgrastim (r-metHuG-CSF): the first 10 years Blood 1996 88: 1907–1929

    CAS  Google Scholar 

  12. Kubota N, Orita T, Hattori K et al. Structural characterization of natural and recombinant human granulocyte colony-stimulating factors J Biochem 1990 107: 486–492

    Article  CAS  Google Scholar 

  13. Souza LM, Boone TC, Gabrilove J et al. Recombinant human granulocyte colony-stimulating factor: effects on normal and leukemic myeloid cells Science 1986 232: 61–65

    Article  CAS  Google Scholar 

  14. Nissen C . Glycosylation of recombinant human granulocyte colony-stimulating factor: implications for stability and potency Eur J Cancer 1994 30A: (Suppl. 3) 12–14

    Google Scholar 

  15. Oh-Eda M, Hasegawa M, Hattori 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 J Biol Chem 1990 265: 11432–11435

    CAS  PubMed  Google Scholar 

  16. Ono M . Physicochemical and biochemical characteristics of glycosylated recombinant human granulocyte colony-stimulating factor (lenograstim) Eur J Cancer 1994 30A: (Suppl. 3) 7–11

    Google Scholar 

  17. Wang C, Eufemi M, Turano C, Giartosio A . Influence of the carbohydrate moiety on the stability of glycoproteins Biochemistry 1996 35: 7299–7307

    Article  CAS  Google Scholar 

  18. Arakawa T, Prestrelski SJ, Narhi LO et al. Cysteine 17 of recombinant human granulocyte colony-stimulating factor is partially solvent-exposed J Protein Chem 1993 12: 525–531

    Article  CAS  Google Scholar 

  19. Akizuki S, Mizorogi F, Inoue T et al. Pharmacokinetics and adverse events following 5-day repeated administration of lenograstim, a recombinant human granulocyte colony-stimulating factor, in healthy subjects Bone Marrow Transplant 2000 26: 939–946

    Article  CAS  Google Scholar 

  20. Gisselbrecht G, Prentice HG, Bacigalupo A et al. Placebo-controlled phase III trial of lenograstim in bone marrow transplantation Lancet 1994 343: 696–700

    Article  CAS  Google Scholar 

  21. Stoppa AM, Blaise D, Viens P et al. Phase I study of in vivo lenograstim (rHuG-CSF) for stem cell collection demonstrates improved neutrophil recovery after autologous bone marrow transplantation Bone Marrow Transplant 1994 13: 541–547

    CAS  PubMed  Google Scholar 

  22. Pedrazzoli P, Gibelli N, Pavesi L et al. Effects of glycosylated and non-glycosylated G-CSFs, alone and in combination with other cytokines, on the growth of human progenitor cells Anticancer Res 1996 16: 1781–1785

    CAS  PubMed  Google Scholar 

  23. Mire-Sluis AR, Das RG, Thorpe R, participants of the collaborative study . The international standard for granulocyte colony-stimulating factor (G-CSF). Evaluation in an international collaborative study J Immunol Meth 1995 179: 117–126

    Article  CAS  Google Scholar 

  24. Querol S, Cancelas JA, Amat L et al. Effect of glycosylation of recombinant human granulocytic colony-stimulating factor on expansion cultures of umbilical cord blood CD34+ cells Haematologica 1999 84: 493–498

    CAS  PubMed  Google Scholar 

  25. Nohynek GJ, Plard JP, Wells MY, Zerial A . Comparison of the potency of glycosylated and nonglycosylated recombinant human granulocyte colony-stimulating factors in neutropenic and nonneutropenic CD rats Cancer Chemother Pharmacol 1997 39: 259–266

    Article  CAS  Google Scholar 

  26. Tanaka H, Tanaka Y, Shinagawa K et al. Three types of recombinant human granulocyte colony-stimulating factor have equivalent biological activities in monkeys Cytokine 1997 9: 360–369

    Article  CAS  Google Scholar 

  27. Høglund M, Smedmyr B, Bengtsson M et al. Mobilization of CD34+ cells by glycosylated and nonglycosylated G-CSF in healthy volunteers – a comparative study Eur J Haematol 1997 59: 177–183

    Article  Google Scholar 

  28. Watts MJ, Addison I, Long SG et al. Crossver study of the haematological effects and pharmacokinetics of glycosylated and non-glycosylated G-CSF in healthy volunteers Br J Haematol 1997 98: 474–479

    Article  CAS  Google Scholar 

  29. Schiødt I, Knudsen LM, Jensen L et al. Flow cytometry comparison of CD34+ subsets in bone marrow and peripheral blood after priming with glycosylated or non-glycosylated rhG-CSF Bone Marrow Transplant 1998 21: 1167–1170

    Article  Google Scholar 

  30. Saccardi R, Avanzi G, Bezzini R . Mobilization of PBSC for hematological rescue: comparison between glycosylated and non-glycosylated G-CSF Bone Marrow Transplant 1997 19: (Suppl. 11) 511

    Google Scholar 

  31. Seymour AM, de Campos E, Thatcher N et al. A single-blind, randomised, vehicle-controlled dose-finding study of recombinant human granulocyte colony-stimulating factor (lenograstim) in patients undergoing chemotherapy for solid cancers and lymphoma Eur J Cancer 1995 31A: 2157–2163

    Article  CAS  Google Scholar 

  32. Neidhart J, Mangalik A, Kohler W et al. Granulocyte colony-stimulating factor stimulates recovery of granulocytes in patients receiving dose-intensive chemotherapy without bone marrow transplantation J Clin Oncol 1989 7: 1685–1692

    Article  CAS  Google Scholar 

  33. Lee S, Im SA, Yoo ES et al. Mobilization kinetics of CD34+ cells in association with modulation of CD44 and CD31 expression during continuous intravenous administration of G-CSF in normal donors Stem Cells 2000 18: 281–286

    Article  CAS  Google Scholar 

  34. Terashi K, Oka M, Ohdo S et al. Close association between clearance of recombinant human granulocyte colony-stimulating factor (G-CSF) and G-CSF receptor on neutrophils in cancer patients Antimicrob Agents Chemother 1999 43: 21–24

    Article  CAS  Google Scholar 

  35. Morstyn G, Foote M, Perkins D, Vincent M . The clinical utility of granulocyte colony-stimulating factor: early achievements and future promise Stem Cells 1994 12: (Suppl. 1) 213–228

    Article  Google Scholar 

  36. Tanaka H, Tokiwa T . Influence of renal and hepatic failure on the pharmacokinetics of recombinant human granulocyte colony-stimulating factor (KRN8601) in the rat Cancer Res 1990 50: 6615–6619

    CAS  PubMed  Google Scholar 

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Acknowledgements

We acknowledge the advice of Dr Willers, Computer Center of the Heinrich-Heine University, on the statistic evaluation of the data, and the excellent collaboration of the nursing, laboratory, and medical staff of the Department of Paediatric Hamatology and Oncology and the Laboratory for Haematology and Experimental Stem Cell Transplantation. This study was supported by Rhône-Poulenc Rorer, distributors of lenograstim.

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Authors and Affiliations

  1. Department of Paediatric Haematology and Oncology, Center of Child Health, Heinrich-Heine University Medical Center, Düsseldorf, Germany

    H Bönig, S Silbermann, S Weller, R Kirschke, G Janssen, U Göbel & W Nürnberger

  2. Division of Paediatric Haematology and Oncology, Center of Child Health, University of Leipzig, Germany

    D Körholz

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Bönig, H., Silbermann, S., Weller, S. et al. Glycosylated vs non-glycosylated granulocyte colony-stimulating factor (G-CSF) – results of a prospective randomised monocentre study. Bone Marrow Transplant 28, 259–264 (2001). https://doi.org/10.1038/sj.bmt.1703136

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