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Correction of neutropenia by GM-CSF in patients with a large granular lymphocyte proliferation

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Summary

The in vivo and in vitro effects of GM-CSF were tested in four patients with large granular lymphocyte proliferation (LGLP) and severe granulocytopenia. All patients had an increased percentage of LGL cells (> 20%), whereas 3/4 patients demonstrated rearranged T-cell-receptor genes. An effect on the peripheral granulocyte counts was noticed in 3/4 patients after 14 days of GM-CSF administration (5Μg/kg/day, subcutaneously); 2.5, 7, and 0.45×109/1, respectively. These changes were associated with a two- to five-fold increase in monocytes and a strong increment in eosinophils. In one patient GM-CSF was not effective in increasing the granulocyte count. B lymphocytes showed a variable increase, ranging from 1.2-fold to 3.8-fold, while the number of NK cells remained almost constant during the GM-CSF treatment. No consistent effect of GM-CSF on T lymphocytes was observed. These data suggest that GM-CSF may be a therapeutic option in some patients with LGLP complicated by granulocytopenia and/or infection.

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References

  1. Baer M, Martinez J, Dadey B, Han T (1991) Cyclosporine reverses agranulocytosis associated with large granular lymphocyte proliferation. Blood 74 [Suppl 1]: 245

    Google Scholar 

  2. Biesma B, de Vries E, Willemze P, Sluiter W, Postmus P, Limburg P, Stern A, Vellenga E (1990) Efficacy and tolerability of recombinant hGM-CSF in patients with chemotherapy-related leukopenia and fever. Eur J Cancer 26: 932–936

    PubMed  Google Scholar 

  3. Bronchud M, Scarffle J, Thatcher N (1987) Phase I/II study of recombinant human granulocyte colony-stimulating factor in patients receiving intensive chemotherapy for small cell lung cancer. Br J Cancer 56: 809–813

    PubMed  Google Scholar 

  4. Champlin R, Nimer S, Ireland P, Oette D, Golde D (1989) Treatment of refractory anemia with recombinant human granulocyte-macrophage-colony-stimulating factor. Blood 73: 694–699

    PubMed  Google Scholar 

  5. Chan W, Link S, Mawle A, Check I, Brynes R, Winton E (1986) Heterogeneity of large granular lymphocyte proliferations: delineation of two major subtypes. Blood 68: 1142–1153

    PubMed  Google Scholar 

  6. Faisal M, Cumberland W, Champlin R, Fahey J (1990) Effect of recombinant human granulocyte-macrophage colony-stimulating factor administration on the lymphocyte subsets of patients with refractory aplastic anemia. Blood 76: 1580–1585

    PubMed  Google Scholar 

  7. Gabrilove J, Jakubowski A, Scher H (1988) 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 318: 1414–1422

    PubMed  Google Scholar 

  8. Ganser A, Volkers B, Greher J (1989) Recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndrome: a phase I/II trial. Blood 73: 31–37

    PubMed  Google Scholar 

  9. Groopman J, Mitsuyasu R, Deleo M (1987) Effect of recombinant human granulocyte-macrophage colony-stimulating factor on myelopoiesis in the acquired immunodeficiency syndrome. N Engl J Med 317: 593–598

    PubMed  Google Scholar 

  10. Hazenberg B, Van Leeuwen M, Van Rijswijk M, Stern A, Vellenga E (1989) Correction of granulocytopenia in Felty's syndrome by granulocyte-macrophage colony-stimulating factor. Simultaneous induction of interleukin-6 release and flare-up of the arthritis. Blood 74: 2769–2770

    PubMed  Google Scholar 

  11. Kaneko T, Ogawa Y, Hirata Y, Hoshino S, Takahashi M, Oshimi K, Mizogichi H (1990) Agranulocytosis associated with granular lymphocyte leukaemia: improvement of peripheral blood granulocyte count with human recombinant granulocyte colonystimulating factor (G-CSF). Br J Haematol 74: 121–122

    PubMed  Google Scholar 

  12. Lanier L, Le A, Civin C, Loken M, Philipps J (1986) The relationship of CD 16 (Leu-11) and Leu 19 (NKH-1) antigen expression on human peripheral blood NK cells and cytotoxic T lymphocytes. J Immunol 136: 4480–4486

    PubMed  Google Scholar 

  13. Loughran T, Starkebaum G (1987) Large granular lymphocyte leukemia: report of 38 cases and review of the literature. Medicine 66: 397–405

    PubMed  Google Scholar 

  14. Newland A, Catovsky D, Linch D, Cawley J, Beverley P, San Miguel J, Gordon-Smith E, Blecher T, Shahriari S, Varadi S (1984) Chronic T-cell lymphocytosis: a review of 21 cases. Br J Haematol 58: 433–446

    PubMed  Google Scholar 

  15. Oostveen J van, Breit T, de Wolf J, Brandt R, Smit J, van Dongen J, Borst J, Melief C (1992) Polyclonal expansion of T-cell receptor-Τδ+ T-lytnphocytes associated with neutropenia and thrombocytopenia. (Submitted)

  16. Oshimi K (1988) Granular lymphocyte proliferative disorders: report of 12 cases and review of the literature. Leukemia 2: 617–627

    PubMed  Google Scholar 

  17. Oshimi K, Oshimi M, Akahoshi M, Kobayashi H, Hirai F, Takaku M, Hattori M, Asano S, Kodo H, Nishinarita S, Lizuka Y, Mizoguchi H (1988) Role of T-cell antigens in the cytolytic activities of large granular lymphocytes (LGL) in patients with LGL lymphocytosis. Blood 71: 473–479

    PubMed  Google Scholar 

  18. Pandolfi F, De Rossi G, Semenzato G, Quinti I, Ranucci A, De Sanctis G, Lopez M, Gasparotto G, Aiuti F (1982) Immunologic evaluation of T-chronic lymphocytic leukemia cells: correlations among phenotype, functional activities, and morphology. Blood 59: 688–695

    PubMed  Google Scholar 

  19. Pandolfi F, Loughran T, Starkebaum G, Chisesi T, Barbui T, Chan W, Brouet J, de Rossi G, McKenna R, Salsano F, Hermann F, van Oostveen J, Schlimok G, Cafaro A, Zambello R, Rodriguez M, Geisler C, Pizzolo G, Steis R, Brisbane J, Kadin M, Mantovani A, Tagawa S, Fauci A, Gastl G, Palutke M, Proctor S, Pross H, Mancini P, Aiuti F, Semenzat G (1990) Clinical course and prognosis of the lymphproliferative disease of granular lymphocytes: a multicenter study. Cancer 65: 341–348

    PubMed  Google Scholar 

  20. Rambaldi A, Pelicci P, Allavena P, Knowles D, Rossini S, Bassan R, Barbui T, Dalla-Favera, Mantovani A (1985) T-cell receptor Β-chain gene rearrangements in lymphoprolifertive disorders of the large granular lymphocytes/natural killer cells. J Exp Med 162: 2156–2162

    PubMed  Google Scholar 

  21. Reynolds C, Foon K (1984) T-Τ lymphoproliferative disease and related disorders in humans and experimental animals: a review of the clinical, cellular, and functional characteristics. Blood 64: 1146–1158

    PubMed  Google Scholar 

  22. Thomssen C, Nissen C, Gratwohl A, Tichelli A, Stern A (1989) Agranulocytosis associated with T-γ-lymphocytosis: no improvement of peripheral blood granulocyte count with humanrecombinant granulocyte-macrophage colony-stimulating factor (GM-CSF). Br J Haematol 71: 157–158

    PubMed  Google Scholar 

  23. Torok-Storb B (1988) Cellular interactions. Blood 72: 373–385

    PubMed  Google Scholar 

  24. Vellenga E, De Wolf J, Beentjes J, Esselink M, Smit J, Halie M (1990) Divergent effects of IL-4 on the G-CSF- and IL-3-supported myeloid colony formation from normal and leukemic bone marrow cells. Blood 75: 633–637

    PubMed  Google Scholar 

  25. Vries E de, Biesma B, Willemze P, Mulder N, Stern A, Aalders J, Vellenga E (1991) A double-blind placebo-controlled study with GM-CSF during chemotherapy for ovarian carcinoma. Cancer Res 51: 116–122

    PubMed  Google Scholar 

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Author notes

  1. J. W. van Oostveen & E. Vellenga

    Present address: Department of Pathology, Free University, University Hospital, Amsterdam, The Netherlands

Authors and Affiliations

  1. Department of Hematology, University of Groningen, The Netherlands

    A. B. Mulder, J. T. M. de Wolf, J. W. Smit & E. Vellenga

  2. Division of Immunology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Huis, Amsterdam, The Netherlands

    J. W. van Oostveen

Authors
  1. A. B. Mulder
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  2. J. T. M. de Wolf
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  3. J. W. Smit
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  4. J. W. van Oostveen
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  5. E. Vellenga
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Mulder, A.B., de Wolf, J.T.M., Smit, J.W. et al. Correction of neutropenia by GM-CSF in patients with a large granular lymphocyte proliferation. Ann Hematol 65, 91–95 (1992). https://doi.org/10.1007/BF01698137

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  • DOI: https://doi.org/10.1007/BF01698137

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