Skip to main content
SpringerLink
Log in

Myelodysplastic Syndromes: Treatment Indication and Choice of Therapy

  • Conference paper
Acute Leukemias IV

Part of the book series: Haematology and Blood Transfusion / Hämatologie und Bluttransfusion ((HAEMATOLOGY,volume 36))

  • 72 Accesses

Abstract

Myelodysplastic syndromes (MDS) are characterized by progressive refractory cytopenias with cellular dysfunction and defective myeloid maturation involving at least two and generally three hematopoietic cell lineages [57,87]. According to the definition of the FrenchAmerican- British Group, patients with less than 5% blast cells in the bone marrow are classified as refractory anemia (RA) or RA with ring sideroblasts, patients with 5–20% blast cells in the marrow as RA with excess of blasts (RAEB), and patients with 20–30% bone marrow blasts as RAEB in transformation (RAEB-T) [10]. Patients with chronic myelomonocytic leukemia (CMML) have a significant proportion of monocytes in the circulation (> 1000/μl), and up to 20% blast cells in the marrow. Although depending on the initial blast cell load 1O%–40% of these patients will proceed to acute nonlymphocytic leukemia (ANNL), infections due to neutropenia and thrombocytopenic bleeding are the most frequent causes of death [52,77].

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Andreeff M, Tafuri A, Hegewisch-Becker S (1990) Colony-stimulating factors (rhG-CSF, rhGM-CSF, rhIL-3, and BCGF) recruit myeloblastic and lymphoblastic leukemia cells and enhance the cytotoxic effects of cytosinearabinoside. Haematol Bluttransfus 33: 747–762

    CAS  Google Scholar 

  2. Antin JH, Smith BR, Holmes W et al. (1988) Phase I/II study of recombinant human granulocyte- macrophage colony stimulating factor in aplastic anemia and myelodysplastic syndrome. Blood 72: 705–713

    PubMed  CAS  Google Scholar 

  3. Antin JH, Weinberg DS, Rosenthal DS (1990) Variable effect of recombinant human granulocyte- macrophage colony-stimulating factor on bone marrow fibrosis in patients with myelodysplasia. Exp Hematol 18: 266–270

    PubMed  CAS  Google Scholar 

  4. Appelbaum FR, Barrall J, Storb R et al. (1990) Bone marrow transplantation for patients with myelodysplasia. Ann Intern Med 112: 590–597

    PubMed  CAS  Google Scholar 

  5. Archimbaud E, Bailly M, Doré JF (1991) Inducibility of Iymphokine activated killer (LAK) cells in patients with acute myelogenous leukaemia in complete remission and its clinical significance. Br J Haematol 77: 328–334

    Article  PubMed  CAS  Google Scholar 

  6. Asano Y, Okamura S, Shibuya T, Harada M, Niho Y (1988) Growth of clonogenic myeloblastic leukemia cells in the presence of human recombinant erythropoietin an addition to various human recombinant hematopoietic factors. Blood 72: 1682–1686

    PubMed  CAS  Google Scholar 

  7. Aul C, Schneider W (1989) The role of low-dose cytosine arabinoside and aggressive chemotherapy in advanced myelodysplastic syndromes. Cancer 64: 1812–1818

    Article  PubMed  CAS  Google Scholar 

  8. Baines A, Masters G, Booth M, Lush C, Jacobs A (1988) Enrichment of progenitor cells from the marrow of patients with myelodysplasia. Br J Haematol 68: 159–164

    Article  PubMed  CAS  Google Scholar 

  9. Begley CG, Metcalf D, Nicola NA (1987) Purified colony-stimulating factors (G-CSF and GM-CSF) induce differentiation in human HL60 leukemic cells with suppression of clonogenicity. In J Cancer 39: 99–105

    CAS  Google Scholar 

  10. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DAG, Granlnick HR, Sultan C (1982) Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 51: 189

    PubMed  CAS  Google Scholar 

  11. Beris P (1989) Primary clonal myelodysplastic syndromes. Semin Hematol 26: 216–233

    PubMed  CAS  Google Scholar 

  12. Besa EC, Nathan F, Sylvester L, Catalano P (1990) Erythroid response of severely anemic or transfusion-dependent patients with myelodysplastic syndrome to recombinant human erythropoietin (Epo) does not cerrelate with baseline serum Epo levels. Blood 76, Suppl 1: 133a

    Google Scholar 

  13. Bessho M, Jinnai I, Matsuda A, Saito M, Hirashima K (1990) Improvement of anemia by recombinant human erythropoietin in patients with myelodysplastic syndromes and aplastic anemia. Int J Cell Cloning 8: 445–458

    Article  PubMed  CAS  Google Scholar 

  14. Bhalla K, Birkhofer M, Arlin Z, Grant S, Lutzky J, Graham G (1988) Effect of recombinant GM-CSF and IL-3 on the metabolism of cytosine arabinoside in normal and leukemic human bone marrow cells. Leukemia 2: 810–813

    PubMed  CAS  Google Scholar 

  15. Boogaerts MA, Nelissen V, Roelant C, Goossens W (1983) Blood neutrophil function in primary myelodysplastic syndromes. Br J Haematol 55: 217–227

    Article  PubMed  CAS  Google Scholar 

  16. Bowen DT, Jacobs A, Cotes MP, Lewis TC (1990) Serum erythropoietin and erythropoiesis in patients with myelodysplastic syndromes. Eur J Haematol 44: 30–32

    Article  PubMed  CAS  Google Scholar 

  17. Bowen D, Culligan D, Jacobs A (1991) The treatment of anaemia in the myelodysplastic syndromes with recombinant human erythropoietin. Br J Haematol 77: 419–423

    Article  PubMed  CAS  Google Scholar 

  18. Bowen D, Ehmer B, Neubert P, Lewis T, Jacobs A (1991) The clearance of a single i.v. bolus of recombinant human erythropoietin from the serum of patients with myelodysplastic syndromes and its effects on erythropoiesis. Exp Hematol 19: 613–616

    PubMed  CAS  Google Scholar 

  19. Brach M, Klein H, Platzer E, Mertelsmann R, Herrmann F (1990) Effect of interleukin-3 on cytosine arabinoside-mediated cytotoxicity of leukemic myeloblasts. Exp Hematol 18: 748–753

    PubMed  CAS  Google Scholar 

  20. Brito-Babapulle F, Lord JAD, Whitmore DN (1989) Treatment of RAEB-T with intensive chemotherapy and GM-CSF. Leukemia Res 13: 605–607

    Article  CAS  Google Scholar 

  21. Broxmeyer HE, Cooper S, Williams DE, Hangoc G, Gutterman JU, Vadhan-Raj S (1988) Growth characteristics of marrow hematopoietic progenitor/precursor cells from patients on a phase I clinical trial with purified recombinant human granulocyt-macrophage colony-stimulating factor. Exp Hematol 16: 594–602

    PubMed  CAS  Google Scholar 

  22. Büchner T, Hiddemann W, Königsmann M, Zühlsdorf M, Wormann B, Boeckmann A, Aguion-Freire E, Innig G, Maschmeyer G, Ludwig WD, Sauerland MC, Heinecke A, Schulz G (1991) Recombinant human granulocyte- macrophage colony-stimulating factor after chemotherapy in patients with acute myeloid leukemia at higher age or after relapse. Blood 78: 1190–1197

    PubMed  Google Scholar 

  23. Cannistra SA, Groshek P, Griffin JD (1989) GM-CSF enhances the cytotoxic effect of cytosine arabinoside in acute myeloblastic leukemia and in myeloid blast crisis of chronic myeloid leukemia. Leukemia 3: 328–334

    PubMed  CAS  Google Scholar 

  24. Carlo-Stella C, Cazzola M, Ganser A, Bergamaschi G, Meloni F, Pedrazzoli P, Bernasconi P, Invernizzi R, Hoelzer D, Ascari E (1988) Recombinant gamma-interferon induces in vitro monocytic differentiation of blast cells from patients with acute nonlymphocytic leukemia and myelodysplastic syndromes. Leukemia 2: 55–59

    PubMed  CAS  Google Scholar 

  25. Castaigne S, Chomienne C, Daniel MT, Ballerini P, Berger R, Fenaux P, Degos L (1990) All-trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia. I. clinical results. Blood 76: 1704–1709

    CAS  Google Scholar 

  26. Cazzola M, Ponchio L, Beguin Y, Rosti V, Bergamaschi G, Liberato NL, Fregoni V, Nalli G, Barosi G, Ascari E (1992) Subcutaneous erythropoietin for the treatment of refractory anemia in hematologic disorders. Results of a phase I/II clinical trial. Blood 79: 29–37

    CAS  Google Scholar 

  27. Cheson BD (1990) The myelodysplastic syndromes: current approaches to therapy. Ann Intern Med 112: 932–941

    PubMed  CAS  Google Scholar 

  28. Cheson BD, Simon R (1987) Low dose ara-C in acute nonlymphocytic leukemia and myelodysplastic syndromes: a review of 20 years experience. Sem Oncol 14 Suppl 1: 126–133

    CAS  Google Scholar 

  29. Delmer A, Karmochkine M, Cadiou M, Gerhartz H, Zittoun R (1990) Recurrent spleen enlargement during cyclic granulocyte-macrophae colony-stimulating factor therapy for myelodysplastic syndromes. Am J Hematol 34: 73–74

    Article  PubMed  CAS  Google Scholar 

  30. De Witte T, Muus P, Haanen C et al. (1988) GM-CSF enhances sensitivity of leukemic clonogenic cells to long-term low dose cytosine arabinoside with sparing of the normal clonogenic cells. Behring Inst Mitt 83: 301–307

    PubMed  Google Scholar 

  31. De Witte T et al. (1990) Intensive antileukemic treatment of patients younger than 65 years with myelodysplastic syndromes and secondary acute myelogenous leukemia. Cancer 66: 831–837

    Article  PubMed  Google Scholar 

  32. Dunbar CE, Smith D, Kimball J, Garrison L, Nienhuis AW, Young NS (1990) Sequential treatment with recombinant human growth factors to compare activity of GM-CSF and IL-3 in the treatment of primary myelodysplasia. Blood 76, Suppl 1: 141a

    Google Scholar 

  33. Estey E, Kurzrock R, Talpaz M, Beran M, Kantarjian H, Keating M, McCredie K, Freireich E, Deisseroth A, Gutterman JU (1989) Therapy of myelodysplastic syndromes (MDS) with GM-CSF. Proc Am Soc Clin Oncol 8, Suppl: 200

    Google Scholar 

  34. Estey EH, Kurzrock R, Talpaz M, McCredie KB, O’Brien S, Kantarjian M, Keating MJ, Deisseroth AB, Gutterman JU (1991) Effects of low doses of recombinant human granulocytemacrophage colony-stimulating factor (GMCSF) in patients with myelodysplastic syndromes. Br J Haematol 77: 291–295

    Article  PubMed  CAS  Google Scholar 

  35. Fenaux P, Lai JL, Jouet JP, Paullet JP, Bauters F (1988) Aggressive chemotherapy in adult primary myelodysplastic syndromes. A report on 29 cases. Blut 57: 297–302

    CAS  Google Scholar 

  36. Fenaux P, Morel P, Rose C, Lai JL, Jouet JP, Bauters F (1991) Prognostic factors in adult de novo myelodysplastic syndromes treated by intensive chemotherapy. Br J Haematol 77: 497–501

    Article  PubMed  CAS  Google Scholar 

  37. Fierro MT, Xin-Sheng L, Lusso P, Bonferroni M, Matera L, Cesano A, Arione R, Forni G, Foa R (1988) In vitro and in vivo susceptibility of human leukemia cells to lymphokine activated killer activity. Leukemia 2: 50–54

    PubMed  CAS  Google Scholar 

  38. Foa R, Meloni G, Tosti S, Novarino A, Fenu S, Gavosto F, Mandelli F (1991) Treatment of acute myeloid leukaemia patients with recombinant interleukin 2: a pilot study. Br J Haematol 77: 491–496

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  40. Ganser A, Ottmann OG, Schulz G, Hoelzer D (1989) Recombinant human granulocyte-macrophage colony-stimulating factor and low-dose cytosine arabinoside in patients with myelodysplastic syndrome. A pilot study. Onkologie 12: 13–15

    CAS  Google Scholar 

  41. Ganser A, Seipelt G, Lindemann A et al. (1990) Effects of recombinant human interieukin-3 in patients with myeiodysplastic syndromes. Blood 76: 455–462

    PubMed  CAS  Google Scholar 

  42. Ganser A, Lindemann A, Seipeit G et al. (1990) The effect of recombinant human interieukin-3 in patients with normal hemopoiesis and in patients with secondary bone marrow failure. Blood 76: 666–676

    PubMed  CAS  Google Scholar 

  43. Ganser A, Seipelt G, Hoelzer D (1991) The role of GM-CSF, G-CSF, interieukin-3 and erythropoietin in Myelodysplastic syndromes. Am J Clin Oncol (CCT) 14, Suppl 1: 34–39

    Article  Google Scholar 

  44. Ganser A, Seipeit G, Eder M, Geissler G, Ottmann OG, Hess U, Hoelzer D (1992) Treatment of myeiodysplastic syndromes with cytokines and cytotoxic drugs. Semin Oncol 19, Suppl 4: 95–101

    PubMed  CAS  Google Scholar 

  45. Gajewski JL, Ho WG, Nimer SD, Hirji KF, Gekeiman L, Jacobs AD, Champlin RE (1989) Efficacy of intensive chemotherapy for acute myelogenous leukemia associated with a preleukemic syndrome. J Clin Oncol 7: 1637–1645

    PubMed  CAS  Google Scholar 

  46. Gerhartz HH, Marcus R, Delmer A, Zwiezina H, de Witte T, Jacobs A, Visani G, Fiere D, Sonneveid P, Labar B, Hoffbrand A V, Fenaux P, Hayat M, Thyss A, Debucher L, Coiffier B, Sizoo W, Willernze R, Ribeiro M, Succiu S, Solbu G, Stem A, Zittoun (1991) Randomized phase II trial with GM-CSF and low-dose Ara-C in patients with “high risk” myelodysplastic syndromes (MDS). In: JH Scarffe (ed) Break-through in cytokine therapy: An overview of GM-CSF. International Congress and Symposium Series Number 170, Royal Society of Medicine Services London pp. 27–40

    Google Scholar 

  47. Greenberg P, Negrin R, Nagler A, Vincent M, Donlon T (1990) Effects of prolonged treatment of myelodysplastic syndromes with recombinant human granulocyte colony-stimulating factor. Int J Cell Cloning 8, Suppl 1: 293–302

    Article  PubMed  Google Scholar 

  48. Groopman JE, Molina JM, Scadden DT (1989) Hematopoietic growth factors. Biology and clinical application. N Engl J Med 321: 1449–1459

    Article  PubMed  CAS  Google Scholar 

  49. Hellstrom E, Birgegärd G, Lockner D, Helmers C, Wide L, Öst A, Wide L (1991) Treatment of myelodysplastic syndromes with recombinant human erythropoietin. Eur J Haematol 47: 355–360

    Article  PubMed  CAS  Google Scholar 

  50. Herrmann F, Lindemann A, Klein H et al. (1989) Effect of recombinant human granulocytemacrophage colony-stimulating factor in patients with myelodysplastic syndrome with excess blasts. Leukemia 3: 335–338

    PubMed  CAS  Google Scholar 

  51. Höffken K, Overkamp F, Stirbu J, Grothey A, Flasshove M, Hoelzer D, Ganser A (1990) Recombinant human granulocyte-macrophage colony-stimulating factor and low-dose cytosinearabinoside in the treatment of patients with myeiodysplastic syndromes. A phase II study. Onkologie 13: 33–37

    Google Scholar 

  52. Hoelzer D, Ganser A, Heimpel H (1984) “Atypical” leukemias: preleukemia, smoldering leukemia and hypoplastic leukemia. Rec Res Cancer Res 93: 69–101

    CAS  Google Scholar 

  53. Hoelzer D, Ganser A, Ottmann OG et al. (1990) Effect of treatment with rhGM-CSF and lowdose cytosine arabinoside on leukemic blast cells in patients with myelodysplastic syndromes. Haematol Blood Transfusion 33: 763–769

    CAS  Google Scholar 

  54. Hoelzer D, Seipeit G, Ganser A (1990) Interieukin-3 alone and in combination with GM-CSF in the treatment of patients with neoplastic disease. In: RP Gale (ed) Acute Myelogenous Leukemia: Progress and Controversies. Wiley-Liss Inc., New York, pp. 467–480

    Google Scholar 

  55. Jacobs A (1991) Genetic lesions in preleukemia. Leukemia 5: 277–282

    PubMed  CAS  Google Scholar 

  56. Janowska-Wieczorek A, Belch AR, Jacobs A, Bowen D, Padua RA, Paietta E, Stanley ER (1991) Increased circulating colony-stimulating factor-l in patients with preleukemia,leukemia, and lymphoid malignancies. Blood 77: 1796–1803

    PubMed  CAS  Google Scholar 

  57. Janssen JWG, Buschle M, Layton M, Drexler HG, Lyons J, Van den Berghe H, Heimple H, Kubanek B, Kleihauer E, Mufti GJ, Bartram CR (1989) Clonal analysis of myelodysplastic syndromes: evidence of muItipotential stem cell origin. Blood 73: 248–254

    PubMed  CAS  Google Scholar 

  58. Karp JE, Burke PJ, Donehower RC (1990) Effects of rhGM-CSF on intracellular ara-C pharmacology in vitro in acute myelocytic leukemia: Comparability with drug-induced humoral stimulatory activity. Leukemia 4: 553–556

    PubMed  CAS  Google Scholar 

  59. Kerndrup G, Hokland P (1988) Natural killer cell-mediated inhibition of bone marrow formation (CFU-GM) in refractory anaemia (Preleukaemia): evidence for patient-specific cell populations. Br J Haematol 69: 457–462

    Article  PubMed  CAS  Google Scholar 

  60. Kobayashi Y, Okabe T, Ozawa K, Chiba S, Hino M, Miyazono K, Urabe A, Takaku F (1989) Treatment of myeiodysplastic syndromes with human granulocyte colony-stimulating factor: a preliminary report. Am J Med 86: 178–182

    Article  PubMed  CAS  Google Scholar 

  61. Kurzrock R, Talpaz M, Estrov Z, Rosenblum MG, Gutterman JU (1991) Phase I study of recombinant human interleukin-3 in patients with bone marrow failure. J Clin Oncol 9: 1241–1250

    PubMed  CAS  Google Scholar 

  62. Kurzrock R, Talpaz M, Gomez JA, Estey EH, O’Brien S, Hirsch-Ginsberg C, Koller E, Freireich EJ, Gutterman JV. Differential doserelated haematological effects of GM-CSF in pancytopenia: evidence supporting the advantage of low- over high-dose administration in selected patients. Br J Haematol 78: 352–358

    Google Scholar 

  63. Laporte JPH, Isnard F, Fenaux P, Woler M, Najman A (1991) Recombinant human erythropoietin at high dose is effective for the treatment of the anemia of myelodysplastic syndromes. Contrib Nephrol 88: 271–272

    PubMed  CAS  Google Scholar 

  64. Lindemann A, Ganse Hoelzer D, Mertelsmann R, Herrmann F (1991) In vivo administration of recombinant human interleukin-3 elicits an acute phase response involving endogenous synthesis of interleukin-6. Eur Cytokine Net 2: 173–176

    CAS  Google Scholar 

  65. List AF, Garewal HS, Sandberg AA (1990) The myelodysplastic syndromes: Biology and implications for management. J Clin Oneal 8: 1424–1441

    CAS  Google Scholar 

  66. Lotzová E, Savary CA, Herberman RB (1987) Inhibition of clonogenic growth of fresh leukemia cells by unstimulated and IL-2 stimulated NK cells of normal donors. Leuk Res 11: 1059–1066

    Article  PubMed  Google Scholar 

  67. Lotzová E, Savary CA, Schachner JR, Huh JO, McCredie K (1991) Generation of cytotoxic NK cells in peripheral blood and bone marrow of patients with acute myelogenous leukemia after continuous infusion with recombinant interleukin-2. Am J Hematol 37: 88–89

    Article  PubMed  Google Scholar 

  68. Maekawa T, Metcalf D (1989) Clonal suppression of HL60 and U937 cells by recombinant human leukemia inhibitory factor in combination with GM-CSF or G-CSF. Leukemia 3: 270–276

    PubMed  CAS  Google Scholar 

  69. Maekawa T, Metcalf D, Gearing DP (1990) Enhanced suppression of human myeloid leukemic cell lines by combinations of IL-6, LIF, GM-CSF and G-CSF. Int J Cancer 45: 353–358

    Article  PubMed  CAS  Google Scholar 

  70. Mayani H, Baines P, Bowen DI, Jacobs A (1989) In vitro growth of myeloid and erythroid progenitor cells from myelodysplastic patients in response to recombinant human granulocytemacrophage colony-stimulating factor. Leukemia 3: 29–32

    PubMed  CAS  Google Scholar 

  71. Merchav S, Nagler A, Fleischer-Kurtz G, Tatarsky I (1989) Regulatory abnormalities in the marrow of patients with myelodysplastic syndromes. Br J Haematol 73: 158–164

    Article  PubMed  CAS  Google Scholar 

  72. Merchav S, Nielsen OJ, Rosenbaum H, Sharon R, Brenner B, Tatarsky I, Scigalla P, Wieczorek L (1990) In vitro studies of erythropoietin-dependent regulation of erythropoiesis in myelodysplastic syndromes. Leukemia 4: 771–774

    PubMed  CAS  Google Scholar 

  73. Merchav S, Wagemaker G, Souza LM, Tatarsky I (1991) Impaired response of myelodysplastic marrow progenitors to stimulation with recombinant haemopoietic growth factors. Leukemia 5: 340–346

    PubMed  CAS  Google Scholar 

  74. Metcalf D (1989) The molecular control of cell division, differentiation commitment and maturation in haemopoietic cells. Nature 339: 27–30

    Article  PubMed  CAS  Google Scholar 

  75. Mitjavila MT, Le couedic JP, Casadevall N, Navarro S, Villeval JL, Dubart A, Vainchainker W (1991) Autocrine stimulation by erythropoietin and autonomous growth of human erythroid leukemic cells in vitro. J Clin Invest 88: 789–797

    Article  PubMed  CAS  Google Scholar 

  76. Morstyn G, Burgess A W (1988) Haemopoietic growth factors: a review. Cancer Res 48: 5624–5637

    PubMed  CAS  Google Scholar 

  77. Mufti GJ, Galton DAG (1986) Myelodysplastic syndromes: Natural history and features of prognostic significance. Clin Haematol 15: 953

    PubMed  CAS  Google Scholar 

  78. Nagler A, Ginzton N, Negrin R, Bang D, Donlon T, Greenberg P (1990) Effects of recombinant human granulocyte colony stimulating factor and granulocyte-monocyte colony stimulating factor on in vitro hemopoiesis in the myelodysplastic syndromes. Leukemia 4: 193–202

    PubMed  CAS  Google Scholar 

  79. Nagler A, Binet C, Mackichan ML, Negrin R, Bangs C, Donlon T, Greenberg P (1990) Impact of marrow cytogenetics and morphology on in vitro hematopoiesis in the myelodysplastic syndromes: comparison between recombinant human granulocyte colony-stimulating factor (CSF) and granulocyte-macrophage CSF. Blood 76: 1299–1307

    PubMed  CAS  Google Scholar 

  80. Nakamaki T, Sakashita A, Sana M, Hino K, Suzuki K, Tomoyasu S, Tsuruoka N, Honma Y, Hozumi M (1989) Granulocyte-colony-stimulating factor and retinoic acid cooperatively induce granulocytic differentiation of acute promyelocytic leukemia cells in vitro. Jpn J Cancer Res 80: 1077–1082

    Article  PubMed  CAS  Google Scholar 

  81. Negrin R, Haeubre DH, Nagler A, Olds LC, Donlon T, Souza LM, Greenberg PL (1989) Treatment of myelodysplastic syndromes with recombinant human granulocyte colony-stimulating factor. A phase I/II trial. Ann Intern Med 110: 976–984

    PubMed  CAS  Google Scholar 

  82. Negrin RS, Haeuber DH, Nagler A, Kobayashi Y, Sklar J, Donlon T, Vincent M, Greenberg PL (1990) Maintenance therapy of patients with myelodysplastic syndromes using recombinant human granulocyte colonystimulating factor. Blood 76: 36–43

    PubMed  CAS  Google Scholar 

  83. Ohno R, Tomonaga M, Kobayashi T et al. (1990) Effect of granulocyte-colony-stimulating factor after intensive induction therapy in relapsed or refractory acute leukemia. NEngl J Med 323: 871–877

    Article  CAS  Google Scholar 

  84. Ohyashiki K, Ohyashiki JH, Toyama K, Takaku F (1989) Hematologic and cytogenetic findings in myelodysplastic syndromes treated with recombinant human granulocyte colonystimulating factor. Jpn J Cancer Res 80: 848

    Article  PubMed  CAS  Google Scholar 

  85. Oster W, Krumwieh D, Brune T, Kraemer HP, Herrmann F, Mertelsmann R (1990) Evaluation of erythropoietin (EPO) in the treatment of patients with myelodysplastic’ syndromes (MDS) - preclinical data supporting a rationale for sequential therapy with granulocyte-macrophage colony-stimulating factor (GM-CSF) and EPO. J Cancer Clin Oneal 116, Suppl: 280

    Google Scholar 

  86. Park LS, Waldron PW, Friend D, Sassenfeld HM, Price V, Anderson D (1989) Interleukin-3. GM-CSF, and G-CSF receptor expression on cell lines and primary leukemia cells: Receptor heterogeneity and relationship to growth factor responsiveness. Blood 74: 56–65

    PubMed  CAS  Google Scholar 

  87. Prchal JT, Trockmorton DW, Carrol AJ, Tuson EW, Gams RA, Prchal JF (1978) A common progenitor for myeloid and lymphoid cells. Nature 274: 590

    Article  PubMed  CAS  Google Scholar 

  88. Rose EH, Rudnick SA, Abels RI, Lessin L, Hoagland HC, Prchal J, Schuster M (1991) Efficacy and safety of recombinant human erythropoietin (r-HuEPO) in anemic patients with myelodysplastic syndromes. Proc of Am Soc Clin Oncol 10: 306

    Google Scholar 

  89. 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. Exp Hematol 19: 273–277

    PubMed  CAS  Google Scholar 

  90. Sachs L (1990) The control of growth and differentiation in normal and leukemic blood cells. Cancer 65: 2196–2206

    Article  PubMed  CAS  Google Scholar 

  91. Sato N, Takatani O, Koeffler HP, Sato H, Asano S, Takaku F (1989) Modulation by retinoids and interferons of alkaline phosphatase activity in granulocytes induced by granulocyte colony-stimulating factor. Exp Hematol 17: 258–262

    PubMed  CAS  Google Scholar 

  92. Sato N, Izukami H, Tani K, Asano S (1991) Regulation of mRNA levels of alkaline phosphatase gene in neutrophilic granulocytes by granulocyte colony-stimulating factor and retinoic acid. Eur J Haematol 46: 107–111

    Article  PubMed  CAS  Google Scholar 

  93. Schipperus M, Sonneveld P, Lindemanns J, Hagemeijer A, Vink N, Pegels J, Abels (1990) The effects of interleukin-3, GM-CSF, and G-CSF on the growth kinetics of colony-forming cells in myelodysplastic syndromes. Leukemia 4: 267–272

    PubMed  CAS  Google Scholar 

  94. Schipperus M, Sonneveld P, Lindemanns J, van Lorn K, Vastuin M, Abels J, Interleukin-6 and interleukin-l enhancement of GM-CSF dependent proliferation of haemopoietic progenitor cells in myelodysplastic syndromes. Br J Haematol 77: 515–522

    Google Scholar 

  95. Schouten HC, Vellenga E, van Rhenen DJ, de Wolf JTM, Coppens PJW, Blijham GH (1991) Recombinant human erythropoietin in patients with myelodysplastic syndromes. Leukemia 5: 432–436

    PubMed  CAS  Google Scholar 

  96. Schuster MW, Thompson JA, Larson R, Allen SL, O’Laughlin R, Israel R, Fefer A (1990) Randomized trial of subcutaneous granulocytemacrophage colony-stimulating factor (GMCSF) versus observation in patients (pts) with myelodysplastic syndrome (MDS). J Cancer Res Clin Oncol 116, Suppl: 1079

    Google Scholar 

  97. Sorskaar D, Forre O, Albrechtsen D, Stavem P (1986) Decreased natural killer cell activity versus normal natural killer cell markers in mononuclear cells from patients with smouldering leukemia. Scand J Haematol 37: 154–161

    Article  PubMed  CAS  Google Scholar 

  98. Stebler C, Tichelli A, Dazzi H, Gratwohl A, Nissen C, Speck B (1990) High-dose recombinant human erythropoietin for treatment of anemiain myelodysplastic syndromes and paroxysmal nocturnal hemoglobinuria: a pilot study. Exp Hematol 18: 1204–1208

    PubMed  CAS  Google Scholar 

  99. Stein RS, Abels RI, Krantz SB (1991) Pharmacologic doses of recombinant human erythropoietin in the treatment of myelodysplastic syndromes. Blood 78: 1658–1663

    PubMed  CAS  Google Scholar 

  100. Tafuri A, Andreeff M (1990) Kinetic rationale for cytokine-induced recruitment of myeloblastic leukemia followed by cycle-specific chemotherapy in vitro. Leukemia 4: 826–834

    PubMed  CAS  Google Scholar 

  101. Tennant GB, Bowen DT, Jacobs A (1991) Colony-cluster ratio and cluster numbers in cultures of circulating myeloid progenitors as indicators of high-risk myelodysplasia. Br J Haematol 77: 296–300

    Article  PubMed  CAS  Google Scholar 

  102. Thomassen MJ, Ahmad M, Barna BP, Antal J, Wiedemann HP, Meeker DP, Klein J, Bauer L, Gibson V, Andresen S, Bukowski RM (1991) Induction of cytokine messenger RNA and secretion in alveolar macrophages and blood monocytes from patients with lung cancer receiving granulocyte-macrophage colony-stimulating factor therapy. Cancer Res 51: 857–862

    PubMed  CAS  Google Scholar 

  103. Thompson JA, Douglas JL, Kidd P et al. (1989) Subcutaneous granulocyte macrophage colonystimulating factor in patients with myelodysplastic syndrome: toxicity, pharmacokinetics, and hematological effects. J Clin Oncol 7: 629–637

    PubMed  CAS  Google Scholar 

  104. Tricot G, Boogaerts MA (1986) The role of aggressive chemotherapy in the treatment of the myelodysplastic syndromes. Br J Haematol 63: 477–483

    Article  PubMed  CAS  Google Scholar 

  105. Vadhan-Raj S, Kellagher MJ, Keating M et al. (1988) Phase I study of recombinant human granulocyte-macrophage colony stimulating factor in patients with myelodysplastic syndrome. N Engl J Med 317: 1545–1552

    Article  Google Scholar 

  106. Valtieri M, Boccoli G, Testa U, Barletta C, Peschle C (1991) Two-step differentiation of AML 193 leukemic line: terminal maturation is induced by positive interaction of retinoic acid with granulocyte colony-stimulating factor (CSF) and vitamin D3 with monocyte CSF. Blood 77: 1804–1812

    PubMed  CAS  Google Scholar 

  107. Van der Lely N, De Witte T, Muus P, Raymakers R, Preijers F (1991) Prolonged exposure to cytosine arabinoside in the presence of hematopoietic growth factors preferentially kills leukemic versus normal c1onogenic cells. Exp Hematol 19: 267–272

    Google Scholar 

  108. Van Kamp H, Tineke C, Prinsze-Postema TC, Kluin PM, den Ottolander GJ, Beverstock GC, WiIlemze R, Fibbe WE (1991) Effect of subcutaneously administered human recombinant erythropoietin on erythropoiesis in patients with myelodysplasia. Br J Haematol 78: 488–493

    Article  PubMed  Google Scholar 

  109. Verhoef GEG, Boogaerts MA (1991) In vivo administration of granulocyte-macrophage colony-stimulating factor enhances neutrophil function in patients with myelodysplastic syndromes. Br J Haematol 79: 177–184

    Article  PubMed  CAS  Google Scholar 

  110. Verhoef GEG, Boogaerts MA (1991) Treatment with granulocyte-macrophage colony-stimulating factor and the adult respiratory distress syndrome. Am J Med 36: 285–287

    CAS  Google Scholar 

  111. Verhoef GEG, Zachee P, Ferrant A et al (1992) Recombinant human erythropoietin for the treatment in the myelodysplastic syndromes: A clinical and erythrokinetic assessment. Ann Hematol 64: 16–21

    Article  PubMed  CAS  Google Scholar 

  112. Willemze R, van der Lely, Zwierzina H, Suciu S, Solbu G, Gerhartz H, Labar B, Visani G, Peetermans ME, Jacob A, Stryckmans P, Fenaux P, Haak HL, Ribeiro MM, Baumelou E, Baccarani M, Mandelli F, Jaksic B, Louwagie A, Thyss A, Hayat M, de Cataldo F, Stern AC, Zittoun R (1992) A randomized phase-I/II multicenter study of recombinant human granulocytemacrophage colony-stimulating factor (GMCSF) therapy for patients with myelodysplastic syndromes and a relatively low risk of acute leukemia. Ann Hematol 64: 173–180

    Article  PubMed  CAS  Google Scholar 

  113. Yoshida Y, Hirashima K, Asano S, Takaku F (1991) A phase II trial of recombinant human granulocyte colony-stimulating factor in the myelodysplastic syndromes. Br J Haematol 78: 378–384

    Article  PubMed  CAS  Google Scholar 

  114. Yuo A, Kitagawa S, Okabe T et al. (1987) Recombinant human granulocyte colony-stimulating factor repairs the abnormalities of neutrophils in patients with myelodysplastic syndromes and chronic myelogenous leukemia. Blood 70: 404–411

    PubMed  CAS  Google Scholar 

  115. Zwierzina H, Herold M, Geissler D, Schollenberger S, Schmalzl F (1991) Soluble interleukin-2 (IL-2) receptor expression in patients with myelodysplastic syndromes is induced by granulocytemacrophage colony-stimulating factor and IL-3. Blood 77: 2795–2796

    PubMed  CAS  Google Scholar 

  116. Zwierzina H, Herold M, Schöllenberger S, Geissler D, Schmalzl F (1991) Detection of soluble IL-2 receptor in the serum of patients with myelodysplastic syndromes: induction under therapy with GM-CSF. Br J Haematol 79: 438–443

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Abteilung für Hämatologie, Zentrum der Inneren Medizin, Klinikum der Johann Wolfgang Goethe Universität, 60596, Frankfurt/Main, Germany

    A. Ganser, O. G. Ottmann & D. Hoelzer

Authors
  1. A. Ganser
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. O. G. Ottmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. Hoelzer
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Internal Medicine, Germany

    T. Büchner

  2. Department of Pediatrics, University of Münster, Albert-Schweitzer-Strasse 33, 48145, Münster, Germany

    G. Schellong  & J. Ritter  & 

  3. Department of Internal Medicine, University of Göttingen, Robert-Koch-Strasse 40, 37075, Göttingen, Germany

    W. Hiddemann  & B. Wörmann  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1994 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Ganser, A., Ottmann, O.G., Hoelzer, D. (1994). Myelodysplastic Syndromes: Treatment Indication and Choice of Therapy. In: Büchner, T., Hiddemann, W., Wörmann, B., Schellong, G., Ritter, J. (eds) Acute Leukemias IV. Haematology and Blood Transfusion / Hämatologie und Bluttransfusion, vol 36. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-78350-0_33

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-78350-0_33

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-78352-4

  • Online ISBN: 978-3-642-78350-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation