The Role of Growth Factors in Myelodysplastic Syndromes: Biological and Clinical Factors

  • G. Verhoef
  • H. Demuynck
  • P. Vandenberghe
  • J. Maertens
  • P. Zachée
  • M. Boogaerts
Conference paper
Part of the Haematology and Blood Transfusion / Hämatologie und Bluttransfusion book series (HAEMATOLOGY, volume 39)

Abstract

The myelodysplastic syndromes (MDS) comprise a heterogeneous group of bone marrow disorders characterized by ineffective and dysplastic hematopoiesis in one or more cell lines. Prognosis in MDS is extremely variable. Evolution to acute nonlymphocytic leukemia (ANLL) occurs in 20–75% of the cases. There is also a high excess mortality rate in these patients compared with that of the general population, especially from infection and/or bleeding, due to cytopenia and defective function of neutrophils.

Keywords

Leukemia Anemia Neutropenia Thrombocytopenia Etoposide 

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References

  1. 1.
    Paquette RL, Koeffler HP (1992) Differentiation therapy. In: Koeffler HP (ed) Heamtology/oncology clinics of North America, pp 687–706. Philadelphia: WB Saunders CompanyGoogle Scholar
  2. 2.
    Aul V, Runde V, Gattermann N (1993) All-trans retinoid acid in patients with myelodysplastic syndromes: results of a pilot study. Blood 82: 2967–2974PubMedGoogle Scholar
  3. 3.
    Hirst WJR, Mufti GJ (1993) Management of myelodysplastic syndromes. British Journal of Haematology 84: 191–196PubMedCrossRefGoogle Scholar
  4. 4.
    Verhoef G, Boogaerts M (1991) In vivo administration of granulocyte-macrophage colony stimulating factor enhances neutrophil function in patients with myelodysplastic syndromes. British Journal of Haematology 79: 177–184PubMedCrossRefGoogle Scholar
  5. 5.
    Verhoef G (1996) rhEPO in the treatment of the myelodysplastic syndromes. In: Smyth JF, Boogaerts MA and Ehmer B (eds) rhErythropoietin in cancer supportive treatment, pp 175–189. New York: Marcel Dekker IncGoogle Scholar
  6. 6.
    Hellström-Lindberg E (1995) Efficacy of erythropoietin in the myelodysplastic syndromes: a meta-analysis of 205 patients from 17 studies. British Journal of Haematology 89: 67–71PubMedGoogle Scholar
  7. 7.
    Ganser A,Hoelzer D (1992) Treatment of myelodysplastic syndromes with hematopoietic growth factors. In: Koeffler HP (ed) Hematology/oncology clinics of North America, pp 633–653. Philadelphia: WB Saunders CompanyGoogle Scholar
  8. 8.
    Kaczmarski RS, Pozniak A, Lakhani A, Harvey E, Mufti GJ (1993) A pilot study of low-dose recombinant human granulocyte-macrophage colony-stimulating factor in chronic neutropenia. British Journal of Haematology 84: 338–340PubMedCrossRefGoogle Scholar
  9. 9.
    Rose C, Wattel E, Bastion Y, Berger E et al. (1994) Treatment with very low-dose GM-CSF in myelodysplastic syndromes with neutropenia. A report on 28 cases. Leukemia 8: 1458–1462PubMedGoogle Scholar
  10. 10.
    Ganser A, Völkers B, Greher J et al. (1989) Recombinant human ganulocyte-macrophage colony stimulating factor in patients with myelodysplastic syndromes-a phase I/II trial. Blood 73: 31–37PubMedGoogle Scholar
  11. 11.
    Rosenfeld CS, Sulecki M, Evans C, Shadduck RK (1991) Comparison of intravenous versus subcutaneous recombinant human granulocyte-macrophage colony-stimulating factor in patients with primary myelodysplasia. Experimental Hematology 19: 273–277PubMedGoogle Scholar
  12. 12.
    Schuster MW, Thompson JA, Larson R et al. (1990) Randomized trial of subcutaneous granulocyte-macrophage colony-stimulating factor versus observation in patients with myelodysplastic syndrome. International Journal of Cancer Research in Clinical Oncology 116 (suppl. II): 1079Google Scholar
  13. 13.
    Greenberg P, Taylor K, Larson R et al. (1993) Phase III randomized multicenter trial of G-CSF vs. Observation for myelodysplastic syndrome. Blood 82 (suppl 1): 196aGoogle Scholar
  14. 14.
    Im T, Yamane T, Mugitani A et al. (1994) Treatment with cytosine arabinoside and granulocyte colony-stimulating factor in patients with myelodysplastic syndrome and its leukemic phase. International Journal of Hematology 60: 215–223PubMedGoogle Scholar
  15. 15.
    Gerhartz HH, Marcus R, Delmer A et al. (1994) A randomized phase II study of low-dose cytosine arabinoside ( LD-AraC) plus granulocyte-macrophage colony stimulating factor (rhGMCSF) in myelodysplastic syndromes with a high risk of developing leukemia. Leukemia 8: 16–23PubMedGoogle Scholar
  16. 16.
    Kurzrock R, Talpaz M, Estrov Z et al. (1991) Phase I study of recombinant human interleukin-3 in patients with bone marrow failure. Journal of Clinical Oncology 9: 1241–1250PubMedGoogle Scholar
  17. 17.
    Willemze R, Fenaux P, Gerhartz H et al. (1992) A randomized phase I/II multicenter study (EORTC 06891) of rh-IL-3 in patients with myelodysplastic syndromes at relatively low risk of developing leukemia (MDS-LR). Blood 80 (suppl): 86aGoogle Scholar
  18. 18.
    Ganser A, Ottmann OG, Seipelt G et al. (1993) Effect of long-term treatment with recombinant interleukin-3 in patients with myelodysplastic syndromes. Leukemia 7: 696–701PubMedGoogle Scholar
  19. 19.
    Legare RD, Gilliland DG (1995) Myelodysplastic syndrome. In Bernstein ID (ed) Current opinion in hematology, pp 283–292. Philadelphia: Current ScienceGoogle Scholar
  20. 20.
    Gordon MS, Nemunaitis J, Hoffman R et al. (1995) A phase I trial of recombinant human interleukin-6 in patients with myelodysplastic syndromes and thrombocytopenia. Blood 85: 3066–3076PubMedGoogle Scholar
  21. 21.
    Hansen PB, Johnson HE, Hippe E et al. (1993) Recombinant human granulocyte-macrophage colony-stimulating factor plus recombinant human erythropoietin may improve anemia in selected patients with myelodysplastic syndromes. American Journal of Hematology 44: 229–236PubMedCrossRefGoogle Scholar
  22. 22.
    Hellström-Lindberg E, Birgegârd G, Carlsson M et al. (1993) A combination of granulocyte colony-stimulating factor and erythropoietin may synergistically improve the anaemia in patients with myelodysplastic syndromes. Leukemia and Lymphoma 11: 221–228PubMedCrossRefGoogle Scholar
  23. 23.
    Negrin RS, Stein R, Vardiman J et al. (1993) Treatment of the anemia of myelodysplastic syndromes using recombinant human granulocyte colony-stimulating factor in combination with erythropoietin. Blood 82: 737–743PubMedGoogle Scholar
  24. 24.
    Imamura M, Kobayashi M, Kobayashi S et al. (1994) Failure of combination therapy with recombinant granulocyte colony-stimulating factor and erythropoietin in myelodysplastic syndromes. Annals of Hematology 68: 163–166PubMedCrossRefGoogle Scholar
  25. 25.
    Musto P, Falcone A, Carotenuto M et al. (1994) Granulocyte colony stimulating factor and erythropoietin for the anemia of myelodysplastic syndromes: a real improvement with respect to erythropoietin alone? [letter] Blood 84: 1687–1688Google Scholar
  26. 26.
    Runde V, Aul C, Ebert A et al. (1995) Sequential administration of recombinant human granulocyte-macrophage colony-stimulating factor and human erythropoietin for the treatment of myelodysplastic syndromes. European Journal of Haematology 54: 39–45PubMedCrossRefGoogle Scholar
  27. 27.
    List AL, Noyes W, Power Jet al. (1993) Combined treatment of myelodysplastic syndromes with recombinant human interleukin-3 and erythropoietin. Blood 82 (suppl): 377aGoogle Scholar
  28. 28.
    Verhoef G, Demuynck H, Zachée P et al. (1993) Treatment of myelodysplastic syndromes with the combination of interleukin-3 and erythropoietin. Blood 82 (suppl): 377aGoogle Scholar
  29. 29.
    Maurer AB, Ganser A, Seipelt G et al. (1995) Changes in erythroid progenitor cell and accessory cell compartments in patients with myelodysplastic syndromes during treatment with all-trans retinoid acid and haemopoietic growth factors. British Journal of Haematology 89: 449–456PubMedCrossRefGoogle Scholar
  30. 30.
    Nand S, Sosman J, Godwin JE, Fisher RI (1994) A phase I/II study of sequential interleukin-3 and granulocyte-macrophage colony-stimulating factor in myelodysplastic syndromes. Blood 83: 357–360PubMedGoogle Scholar
  31. 31.
    Verhoef G, van den Berghe H, Boogaerts M (1992) Cytogenetic effects of cells derived from patients with myelodysplastic syndromes during treatment of hematopoietic growth factors. Leukemia 6: 766–770PubMedGoogle Scholar
  32. 32.
    Gassmann W et al. (1996) Intensive chemotherapy and bone marrow transplantation for myelodysplastic syndromes. Seminars in Hematology 33: 196–205PubMedGoogle Scholar
  33. 33.
    Boogaerts M et al. (1996) Treatment and prognostic factors in myelodysplastic syndromes. Löwenberg B: Acute myelogenous leukaemia and myelodysplasia. Bailiere’s clinical haematology, Baillière Tindall, London 9: 161–183Google Scholar
  34. 34.
    Runde V et al. (1995) Allogeneic bone marrow transplantation for patients with myelodysplastic syndromes or leukemia following MDS: a survey for the working party on chronic leukemia of the EBMTG. Bone Marrow Transplantation 15 (suppl.2): 86Google Scholar
  35. 35.
    Bearman S et al. (1988) Regimen-related toxicity in patients undergoing bone marrow transplantation. Journal of Clinical Oncology 6: 1562–1568PubMedGoogle Scholar
  36. 36.
    Kernnan N et al. (1993) Analysis of 462 transplants from unrelated donors facilitated by the national marrow donor program. New England Journal of Medicine 328: 593–602CrossRefGoogle Scholar
  37. 37.
    Casper J et al. (1995) Unrelated bone marrow transplants for children with leukemia or myelodysplasia. Blood 85: 2354–2363PubMedGoogle Scholar
  38. 38.
    Geller R et al. (1988) Successful marrow transplantation for acute myelocytic leukemia following therapy for Hodgkin’s disease. Journal of Clinical Oncology 6: 1558–1561PubMedGoogle Scholar
  39. 39.
    McMillan A et al. (1990) High dose chemotherapy and autologous bone marrow transplantation in acute myeloid leukemia. Blood 76: 480–488PubMedGoogle Scholar
  40. 40.
    de Witte T et al. (1995’) Autologous BMT for patients with myelodysplastic syndromes or acute myeloid leukemia following MDS.A report from the chronic and acute leukaemia working party of the EBMT. Experimental Hematology 23:904Google Scholar
  41. 41.
    Gianni A et al. (1989) Granulocyte-macrophage colony-stimulating factor to harvest circulating hemopoietic stem cells for autotransplantation. Lancet ii: 580–585CrossRefGoogle Scholar
  42. 42.
    Sheridan W et al. (1992) Effect of peripheral-blood progenitor cells mobilised by filgrastim (G-CSF) on platelet recovery after high-dose chemotherapy. Lancet 339: 640–644PubMedCrossRefGoogle Scholar
  43. 43.
    Korbling M et al. (1991) Autologous blood stem cell versus purged bone marrow transplantation in standard risk AML: influence of source and cell composition of the autograft on hemopoietic reconstitution and disease-free survival. Bone Marrow Transplantation 7: 343–349PubMedGoogle Scholar
  44. 44.
    Sanz M et al. (1993) Busulfan plus cyclophosphamide followed by autologous stem cell transplantation for patients with acute myeloblastic leukemia in first complete remission: a report from a single institution. Journal of Clinical Oncology 11: 1661–1667PubMedGoogle Scholar
  45. 45.
    Reiffers J et al. (1994) Is there a place for blood stem-cell transplantation for the younger adult patient with acute myelogenous leukemia? BGMT Group. Journal of Clinical Oncology 12: 1100–1102PubMedGoogle Scholar
  46. 46.
    Demuynck H et al. (1996) Feasibility of peripheral blood progenitor cell harvest and transplantation in patients with poor-risk myelodysplastic syndromes. British Journal of Haematology 92: 351–359PubMedCrossRefGoogle Scholar
  47. 47.
    de Witte T et al. (1995b) Intensive remission-induction chemotherapy followed by autologous or allogeneic stem cell transplantation for high risk MDS and AML secondary to MDS in patients 003C 60 years. A Joint study of the EORTC LCG and the EBMT. Blood 86 (suppl. 1): 618aGoogle Scholar
  48. 48.
    Delforge M et al. (1995) Polyclonal primitive hemopoietic progenitors can be detected in mobilized peripheral blood from patients with high-risk myelodysplastic syndromes. Blood 86: 3660–3667PubMedGoogle Scholar
  49. 49.
    Allen R et al. (1992) Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen-receptor gene correlates with X chromosome inactivation. American Journal of Human Genetics 51: 1229–1304PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • G. Verhoef
  • H. Demuynck
  • P. Vandenberghe
  • J. Maertens
  • P. Zachée
  • M. Boogaerts

There are no affiliations available

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