Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor Following Chemotherapy in Patients with High-Risk AML

  • T. Büchner
  • W. Hiddemann
  • M. Koenigsmann
  • M. Zühlsdorf
  • B. Wörmann
  • A. Boeckmann
  • E. Aguion Freire
  • G. Innig
  • G. Maschmeyer
  • W.-D. Ludwig
  • M.-C. Sauerland
  • A. Heinecke
  • G. Schulz
Conference paper
Part of the Haematology and Blood Transfusion / Hämatologie und Bluttransfusion book series (HAEMATOLOGY, volume 34)

Abstract

Despite great efforts in supportive care for patients with acute myeloid leukemia (AML), early death during the phase of induction treatment still remains an unsolved therapeutic problem. Multicenter trials [1–6] show early deaths in 17%–32% of patients at all ages and 27%–52% in those 60 years of age and older. In addition, intensive chemotherapy for relapsed and refractory AML produced up to 56% complete remissions (CR) but also 29% early deaths [7, 8] or probably more [9]. After postinduction intensification chemotherapy 5%–20% of patients died from toxicity [6]. Infections due to neutropenia were responsible for most of the early deaths during induction therapy [1–4] and represent the major dose-limiting toxicity. Thus, reducing the phase of critical neutropenia would allow more effective antileukemic chemotherapy.

Keywords

Leukemia Oncol Sarcoma Glutamine Neutropenia 

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References

  1. 1.
    Rai KR, Holland JF, Glidewell O, Weinberg V, Brunner K, Obrecht JP, Preisler HD, Nawabi IW, Prager D, Carey RW, Cooper MR, Haurani F, Hutchison JL, Silver RT, Falkson G, Wiernik P, Hoagland HC, Blumfield CD, James GW, Gottlieb A, Ramanan SV, Blom J, Nissen NI, Bank A, Allison RR, Kung F, Henry P, McIntyre OR, Kaan SK (1981) Treatment of acute myelocytic leukemia: a study by Cancer and Leukemia Group B. Blood 58: 1203PubMedGoogle Scholar
  2. 2.
    Yates J, Glidewell O, Wiernik P, Cooper MR, Steinberg D, Dosick H, Levi R, Hoagland C, Henry P, Gottlieb A, Cornell C, Behrenberg J, Hutchinson JL, Raich P, Nissen N, Allison RR, Frelick R, James GW, Falksohn G, Silver RT, Haurani F, Green M, Anderson E, Leone L, Holland JF (1982) Cytosine-arabinoside with daunorubicin or adriamycin for therapy of acute myelocytic leukemia: a CALGB-study. Blood 60: 454PubMedGoogle Scholar
  3. 3.
    Cassileth PA, Begg CB, Bennett JM, Bozdech M, Kahn SB, Weiler C, Glick JH (1984) A randomized study of the efficacy of consolidation therapy in adult acute nonlymphocytic leukemia. Blood 63: 843PubMedGoogle Scholar
  4. 4.
    Büchner T, Urbanitz D, Hiddemann W, Rühl H, Ludwig WD, Fischer J, Aul HC, Vaupel HA, Kruse R, Zeile G, Nowrousian MR, König HJ, Walter M, Wendt FC, Sodomann H, Hossfeld DK, von Paleske A, Loeffler H, Gassmann W, Hellriegel KP, Fülle HH, Lunscken C, Emmerich B, Pralle H, Pees HW, Pfreundschuh M, Bartels H, Koeppen HM, Schwerdtfeger R, Donhuijsenant R, Mainzer K, Bartel B, Koeppler H, Zurborn KH, Ranft K, Thiel E, Heinecke A (1985) Intensified induction and consolidation with or without maintenance chemotherapy for acute myeloid leukemia (AML): two multicenter studies of the German AML Cooperative Group. J Clin Oncol 3: 1583PubMedGoogle Scholar
  5. 5.
    Rees JKH, Gray R (1987) Comparison of 1 + 5 DATand 3 + 10 DAT followed by COAP or MAZE. Consolidation therapy in the treatment of acute myeloid leukemia: MRC ninth AML trial. Semin Oncol 14: 32PubMedGoogle Scholar
  6. 6.
    Preisler H, Davis RB, Kirshner J, Dupre Richards III F, Hoagland HC, Copel S, Levi AN, Carey R, Schulman P, Gottlieb AJ, McIntyre OR, Cancer and Leukemia Group B (1987) Comparison of three remission induction regimens and two post induction strategies for the treatment of acute nonlymphocytic leukemia: a Cancer and Leukemia Group B study. Blood 69: 1441Google Scholar
  7. 7.
    Hiddemann W, Kreutzmann H, Straif K, Ludwig WD, Mertelsmann R, DonhuijsenAnt R, Lengfelder E, Arlin Z, Büchner T (1987) High-dose cytosine-arabinoside and mitoxantrone: a highly effective regimen in refractory acute myeloid leukemia. Blood 69: 744PubMedGoogle Scholar
  8. 8.
    Hiddemann W, Kreutzmann H, Straif K, Ludwig WD, Mertelsmann R, Planker M, Donhuijsenant R, Lengfelder E, Arlin Z, Büchner T (1987) High-dose cytosine-arabinoside in combination with mitoxantrone for the treatment of refractory myeloid and lymphoblastic leukemia. Semin Oncol 14: 73PubMedGoogle Scholar
  9. 9.
    Capizzi RL, Powell BL (1987) Sequential high-dose Ara-C and asparaginas versus high-dose Ara-C alone in the treatment of patients with relapsed and refractory acute leukemias. Semin Oncol 14: 40PubMedGoogle Scholar
  10. 10.
    Büchner T, Hiddemann W, Zühlsdorf M, Königsmann M, Boeckmann A, van de Loo J, Schulz G (1988) Human recombinant granulocyte-macrophage colony-stimulating factor ( GM-CSF) treatment of patients with acute leukemias in aplasia and at high risk of early death. Behring Inst Mitt 83: 308Google Scholar
  11. 11.
    Büchner T, Hiddemann W, Königsmann M, Zühlsdorf M, Wörmann B, Boeckmann A, van de Loo J, Maschmeyer G, Wendt F, Schulz G (1988) Human recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) for acute leukemias in aplasia and at high risk of early death. Blood 72 (Suppl 1): 354Google Scholar
  12. 12.
    Donahue RE, Wang EA, Stone DK, Kamen R, Wong GG, Sehgal PK, Nathan DG, Clark SC (1986) Stimulation of haematopoiesis in primates by continuous infusion of recombinant human GM-CSE Nature 321: 872Google Scholar
  13. 13.
    Mayer P, Lam C, Obenaus H, Liehe E, Besemer J (1987) Recombinant human GMCSF induces leukocytosis and activates peripheral blood polymorph nuclear neutrophils in non-human primates. Blood 206Google Scholar
  14. 14.
    Monroy RL, Skelly RR, Taylor P, Dubois A, Donahue RE, MacVittey TJ (1988) Recovery from severe hematopoietic suppression using recombinant human granulocyte-macrophage colony-stimulating factor. Exp Hematol 16: 344PubMedGoogle Scholar
  15. 15.
    Nienhues AW, Donahue RE, Karlson SC, Agricola B, Antinoff N, Pierce JE Turner P, Anderson WF, Nahtan DG (1987) Recombinant human granulocyte-macrophage colony-stimulating factor ( GM-CSF) shortens the period of neutropenia after autologous bone marrow transplantation on a primate model. J Clin Invest 80: 573CrossRefGoogle Scholar
  16. 16.
    Monroy RL, Skelly RR, Macvittie TJ, Davies TA, Sauber JJ, Clark SC, Donahue RE (1987) The effect of recombinant GM-CSF on recovery of monkeys transplanted with autologous bone marrow. Blood 70: 1696PubMedGoogle Scholar
  17. 17.
    Groopmann JE, Mitsuyasu RT, DeLeo MJ, Oette DH, Golde DW (1987) Effect of recombinant human granulocyte-macrophage colony-stimulating factor on myelopoiesis in the acquired immunodeficiency syndrome. N Engl J Med 318: 593CrossRefGoogle Scholar
  18. 18.
    Champlin RE, Nimer SD, Ireland P, Oette DH, Golde DW (1989) Treatment of refractory aplastic anemia with recombinant human granulocyte-macrophage colony-stimulating factor. Blood 73: 694PubMedGoogle Scholar
  19. 19.
    Vadhan-Raj SV, Büccher S, Broxmeyer HE, LeMaistre A, Lepe-Zuniga JL, Ventura G, Jeha S, Horowitz LJ, Trujillo JM, Gillis S, Hittelman WN, Gutterman JU (1988) Stimulation of myelopoiesis in patients with aplastic anemia by recombinant human granulocyte-macrophage colony-stimulating factor. N Engl J Med 319: 1628PubMedCrossRefGoogle Scholar
  20. 20.
    Antman K, Griffin J, Elias A, Socinski M, Whitley M, Ryan L, Cannistra S, Oette D, Frei E, Schnipper L (1987) Use of rGM-CSF to ameliorate chemotherapy-induced myelosuppression in sarcoma patients. Blood 70 (Suppl 1): 373Google Scholar
  21. 21.
    Brandt SJ, Peters WP, Atwater SK, Kurtz-berg J, Borowitz MJ, Jones RB, Shapaal EJ, Bast RC, Gilbert CJ, Oette DH (1988) Effect of recombinant human granulocyte-macrophage colony-stimulating factor on hematopoietic reconstitution after high-dose chemotherapy and autologous bone marrow transplantation. N Engl J Med 318: 869PubMedCrossRefGoogle Scholar
  22. 22.
    Vadhan-Raj S, Keating M, LeMaistre A, Hittelmann W, McCredie K, Trujillo JM, Broxmeyer HE, Henney C, Gutterman JV (1987) Effects of recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes. N Engl J Med 317: 1545–1552PubMedCrossRefGoogle Scholar
  23. 23.
    Hölzer D, Ganser A, Völkers B, Greher J, Walther F (1988) In vitro and in vivo action of recombinant human GM-CSF in patient with myelodysplastic syndromes. Blood Cells 14: 551Google Scholar
  24. 24.
    Ganser A, Völkers B, Grober J, Ottmann OG, Walther F, Becker R, Bergmann L, Schulz G, Hölzer D (1989) Recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes; a phase I/II trial. Blood 738 31Google Scholar
  25. 25.
    Herrmann FH, Lindemann A, Klein H, Lübbert M, Schulz G, Mertelsmann R (1989) Effect of recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndrome with excess blasts. Leukemia 3: 335PubMedGoogle Scholar
  26. 26.
    Griffin HD, Young D, Herrmann F, Wiper D, Wagner K, Sabbath KD (1986) Effects of recombinant human GM-CSF on proliferation of clonogenic cells in acute myeloblastic leukemia. Blood 67: 1448PubMedGoogle Scholar
  27. 27.
    Kelleher C, Miyauchi J, Wong G, Clark S, Minden MD, McCuloch EA (1987) Synergism between recombinant growth factors GM-CSF and G-CSF, acting on the blast cells of acute myeloblastic leukemia. Blood 69: 1489Google Scholar
  28. 28.
    Miyauchi J, Kelleher CA, Yang Y, Wong GC, Clark SC, Minden MD, Minken S, McCulloch EA (1987) The effect of three recombinant growth factors, IL-3, GM-CSF, and G-CSF, on the blast cells of acute myeloblasts leukemia maintained in short-term suspension culture. Blood 70: 657Google Scholar
  29. 29.
    Vellenga E, Ostapovicz D, O’Rurke B, Griffin B (1987) Effects of recombinant IL-3, GM-CSF, and G-CSF on proliferation of leukemic clonogenic cells in short-term and long-term cultures. Leukemia 1: 584Google Scholar
  30. 30.
    Vellenga E, Young DC, Wagner K, Wiper D, Ostapovicz D, Griffin JD (1987) The effect of GM-CSF and G-CSF in promoting growth of clonogenic cells in acute myeloblastic leukemia. Blood 69: 1771PubMedGoogle Scholar
  31. 31.
    Murohashi I, Nagata K, Suzuki T, Maruyama Y, Nara N (1988) Effects of recombinant G-CSF and GM-CSFon the growth in methyl cellulose and suspension of the blast cells inacute myeloblastic leukemia. Leuk Res 12: 433PubMedCrossRefGoogle Scholar
  32. 32.
    Young DC, Demetri DG, Ernst TJ, Cannistra SA, Griffin JD (1988) In vitro expression of colony-stimulating factor genes by humanacute myeloblastic leukemia cells. Exp Hematol 16: 378PubMedGoogle Scholar
  33. 33.
    Cantrell MA, Anderson D, Cerretti DP, Price V, McKereghan K, Tushinski RJ, Mochizuki DY, Larsen A, Grabstein K, Gillis S, Cosman D (1985) Cloning, sequence, and expression of a human granulocyte/macrophage colony-stimulating factor. Proc Natl Acad Sci USA 82: 6250PubMedCrossRefGoogle Scholar
  34. 34.
    Hiddemann W, Maschmeyer G, Pfreundschuh M, Ludwig WD, Büchner T (1987) High-dose cytosine arabinoside and mitoxantrone (HAM) for treatment of refractoryacute leukemias: results of a multicenterstudy and preliminary data on a sequential application suggesting increased antileukemic efficacy. Blood 70 (Suppl 1): 778Google Scholar
  35. 35.
    Oken MM, Creech RH (1982) Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 5: 649PubMedCrossRefGoogle Scholar
  36. 36.
    Bennett JM, Catovsky D, Daniel D, Flandrin G, Galton DAG, Gralnick HR, Sultan C (1976) Proposals for the classification of the acute leukemias. Br J Haematol 33: 451PubMedCrossRefGoogle Scholar
  37. 37.
    Büchner T, Hiddemann W, Wörmann B, Kleinmeyer B, Schumann J, Göhde W, Ritter J, Müller KM, von Bassewitz DB, Rössner A, Grundmann E (1985) Differential pattern of DNA aneuploidy in human malignancies. Pathol Res Pract 179: 310PubMedCrossRefGoogle Scholar
  38. 38.
    Hiddemann W, Wörmann B, Göhde W, Büchner T (1986) DNA aneuploidies in adultpatients with acute myeloid leukemia: incidence and relation to patient characteristics and morphologic subtypes. Cancer 57: 2146PubMedCrossRefGoogle Scholar
  39. 39.
    Hiddemann W, Schumann J, Andreeff M, Barlogie B, Herman CJ, Leif RC, Mayall BH, Sandberg AA (1984) Convention on nomenclature for DNA cytometry. Cancer Genet Cytogenet 13: 181PubMedCrossRefGoogle Scholar
  40. 40.
    Rowley SD, Zühlsdorf M, Brayne HG, Colvin OM, Davis J, Jones RJ, Saral R, Sensenbrenner LL, Yeager A, Santos GW (1987) CFU-GM content of bone marrow graft correlates with time to hematological reconstitution following autologous bone marrow transplantation with 4-hydroxyperoxyclyclo phosphamide-purged bone marrow. Blood 70: 271PubMedGoogle Scholar
  41. 41.
    Estey EH, Dixon D, Kantorjian HM, Keating MJ, McCredie K, Bodey GP, Kurzrock R, Talpaz M, Freireich EJ, Deisseroth AB, Gutterman JU (1998) Treatment of poor-prog nosis, newly diagnosed acute myeloid leukemia with Ara-C and recombinant human granulocyte-macrophage colony stimulating factor. Blood 75: 1766Google Scholar
  42. 42.
    Peters WP, Shogan J, Shpall EJ, Jones RB, Kim CS (1988) Recombinant human granulocyte-macrophage colony-stimulating factor produces fever. Lancet 1: 950PubMedCrossRefGoogle Scholar
  43. 43.
    Lieschke GJ, Cebon J, Morstyn G (1969) Characterization of the clinical effects afterthe first dose of bacterially synthesized recombinant human granulocyte-macrophage colony-stimulating factor. Blood 74: 2634Google Scholar
  44. 44.
    Zühlsdorf M, Hiddemann W, Königsmann M, Wörmann B, Büchter U, Büchner T (1990) Different responsiveness of AML blasts to rhGM-CSF pre and post chemotherapy. Proc Am Assoc Cancer Res 31: 1159Google Scholar
  45. 45.
    Bettelheim P, Valent P, Andreeff M, Tafuri A, Haimi J, Gorischek C, Muhm M, Sillaber C, Haas O, Vieder L, Maurer D, Schulz G, Speiser W, Geissler K, Kier P, Hinterberger W, Lechner K (1991) Recombinant human granulocyte-macrophage colony-stimulating factor in combination with standard induction chemotherapy in de novo acute myeloid leukemia. Blood 77, 4: 700PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1992

Authors and Affiliations

  • T. Büchner
    • 1
  • W. Hiddemann
    • 1
  • M. Koenigsmann
    • 1
  • M. Zühlsdorf
    • 1
  • B. Wörmann
    • 1
  • A. Boeckmann
    • 1
  • E. Aguion Freire
    • 1
  • G. Innig
    • 1
  • G. Maschmeyer
    • 2
  • W.-D. Ludwig
    • 3
  • M.-C. Sauerland
    • 4
  • A. Heinecke
    • 4
  • G. Schulz
    • 5
  1. 1.Departments of Hematology/OncologyUniversity of MünsterGermany
  2. 2.Evangelisches Krankenhaus Essen-WerdenGermany
  3. 3.Free University HospitalSteglitz, West BerlinGermany
  4. 4.Department of BiostatisticsUniversity of MünsterAG MarburgGermany
  5. 5.BehringwerkeAG MarburgGermany

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