Seminars in Hematology
Volume 44, Issue 3 , Pages 183-192 , July 2007

Current Status of Growth Factors in the Treatment of Acute Myeloid and Lymphoblastic Leukemia

  • Oliver G. Ottmann

      Affiliations

    • Department of Hematology and Oncology, Johann Wolfgang Goethe University, Frankfurt/Main, Germany.
    • Corresponding Author InformationAddress correspondence to Oliver G. Ottmann, MD, Medizinische Klinik II, Abteilung Hämatologie und Onkologie, Johann Wolfgang Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
  • ,
  • Gesine Bug

      Affiliations

    • Department of Hematology and Oncology, Johann Wolfgang Goethe University, Frankfurt/Main, Germany.
  • ,
  • Jürgen Krauter

      Affiliations

    • Department of Hematology, Hemostasis and Oncology of Hannover Medical School, Hannover, Germany.

References 

  1. Smith TJ, Khatcheressian J, Lyman GH, Ozer H, Armitage JO, Balducci L, et al. 2006 update of recommendations for the use of white blood cell growth factors: An evidence-based clinical practice guideline. J Clin Oncol. 2006;24:3187–3205
  2. Zittoun R, Suciu S, Mandelli F, de Witte T, Thaler J, Stryckmans P, et al. Granulocyte-macrophage colony-stimulating factor associated with induction treatment of acute myelogenous leukemia: a randomized trial by the European Organization for Research and Treatment of Cancer Leukemia Cooperative Group. J Clin Oncol. 1996;14:2150–2159
  3. Stone RM, Berg DT, George SL, Dodge RK, Paciucci PA, Schulman P, et al. Granulocyte-macrophage colony-stimulating factor after initial chemotherapy for elderly patients with primary acute myelogenous leukemia (Cancer and Leukemia Group B). N Engl J Med. 1995;332:1671–1677
  4. Rowe JM, Andersen JW, Mazza JJ, Bennett JM, Paietta E, Hayes FA, et al. A randomized placebo-controlled phase III study of granulocyte-macrophage colony-stimulating factor in adult patients (> 55 to 70 years of age) with acute myelogenous leukemia: A study of the Eastern Cooperative Oncology Group (E1490). Blood. 1995;86:457–462
  5. Lowenberg B, Boogaerts MA, Daenen SM, Verhoef GE, Hagenbeek A, Vellenga E, et al. Value of different modalities of granulocyte-macrophage colony-stimulating factor applied during or after induction therapy of acute myeloid leukemia. J Clin Oncol. 1997;15:3496–3506
  6. Amadori S, Suciu S, Jehn U, Stasi R, Thomas X, Marie JP, et al. Use of glycosylated recombinant human G-CSF (lenograstim) during and/or after induction chemotherapy in patients 61 years of age and older with acute myeloid leukemia: Final results of AML-13, a randomized phase-3 study. Blood. 2005;106:27–34
  7. Harousseau JL, Witz B, Lioure B, Hunault-Berger M, Desablens B, Delain M, et al. Granulocyte colony-stimulating factor after intensive consolidation chemotherapy in acute myeloid leukemia: Results of a randomized trial of the Groupe Ouest-Est Leucemies Aigues Myeloblastiques. J Clin Oncol. 2000;18:780–787
  8. Goldstone AH, Burnett AK, Wheatley K, Smith AG, Hutchinson RM, Clark RE. Attempts to improve treatment outcomes in acute myeloid leukemia (AML) in older patients: The results of the United Kingdom Medical Research Council AML11 trial. Blood. 2001;98:1302–1311
  9. Usuki K, Urabe A, Masaoka T, Ohno R, Mizoguchi H, Hamajima N, et al. Efficacy of granulocyte colony-stimulating factor in the treatment of acute myelogenous leukaemia: A multicentre randomized study. Br J Haematol. 2002;116:103–112
  10. Bradstock K, Matthews J, Young G, Lowenthal R, Baxter H, Arthur C, et al. Effects of glycosylated recombinant human granulocyte colony-stimulating factor after high-dose cytarabine-based induction chemotherapy for adult acute myeloid leukaemia. Leukemia. 2001;15:1331–1338
  11. Heil G, Hoelzer D, Sanz MA, Lechner K, Liu Yin JA, Papa G, et al. A randomized, double-blind, placebo-controlled, phase III study of filgrastim in remission induction and consolidation therapy for adults with de novo acute myeloid leukemia (The International Acute Myeloid Leukemia Study Group). Blood. 1997;90:4710–4718
  12. Godwin JE, Kopecky KJ, Head DR, Willman CL, Leith CP, Hynes HE, et al. A double-blind placebo-controlled trial of granulocyte colony-stimulating factor in elderly patients with previously untreated acute myeloid leukemia: A Southwest Oncology Group study (9031). Blood. 1998;91:3607–3615
  13. Dombret H, Chastang C, Fenaux P, Reiffers J, Bordessoule D, Bouabdallah R, et al. A controlled study of recombinant human granulocyte colony-stimulating factor in elderly patients after treatment for acute myelogenous leukemia (AML Cooperative Study Group). N Engl J Med. 1995;332:1678–1683
  14. Bradstock KF. The use of hematopoietic growth factors in the treatment of acute leukemia. Curr Pharm Des. 2002;8:343–355
  15. Bettelheim P, Valent P, Andreeff M, Tafuri A, Haimi J, Gorischek C, et al. Recombinant human granulocyte-macrophage colony-stimulating factor in combination with standard induction chemotherapy in de novo acute myeloid leukemia. Blood. 1991;77:700–711
  16. varado Ibarra ML, Borbolla E, Lopez-Hernandez MA, Gonzalez-Avante CM, Flores Chapa JD, Trueba CE, et al. Neutrophil recovery time and adverse side effects in acute leukemia patients treated with intensive chemotherapy and concomitant G or GM-CSF. Rev Invest Clin. 1999;51:77–80
  17. Martino R, Brunet S, Sureda A, Guardia R, Aventiin A, Soler J, et al. Hematopoietic growth factor (G-CSF or GM-CSF) after salvage chemotherapy in refractory or relapsed adult de novo acute leukemia. Leuk Lymphoma. 1996;20:321–326
  18. Schlenk RF, Döhner K, Groner S, Hartmann PC, Krauter J, Ganser A, et al. Impact of Pegfilgrastim on hematological reconstitution and incidence of neutropenic fever after consolidation therapy with high-dose cytarabine in acute myeloid leukemia: Comparative analysis between AMLSG 07-04 and the German intergroup trial. Blood. 2006;108:572a;(abstr 2020)
  19. Heil G, Hoelzer D, Sanz MA, Lechner K, Noens L, Szer J, et al. Long-term survival data from a phase 3 study of Filgrastim as an adjunct to chemotherapy in adults with de novo acute myeloid leukemia. Leukemia. 2006;20:404–409
  20. Heuser M, Ganser A. Colony-stimulating factors in the management of neutropenia and its complications. Ann Hematol. 2005;84:697–708
  21. Wandt H, Frank M, Ehninger G, Schneider C, Brack N, Daoud A, et al. Safety and cost effectiveness of a 10 × 10(9)/L trigger for prophylactic platelet transfusions compared with the traditional 20 × 10(9)/L trigger: a prospective comparative trial in 105 patients with acute myeloid leukemia. Blood. 1998;91:3601–3606
  22. Kaushansky K. Thrombopoietin. N Engl J Med. 1998;339:746–754
  23. Archimbaud E, Ottmann OG, Yin JA, Lechner K, Dombret H, Sanz MA, et al. A randomized, double-blind, placebo-controlled study with pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) as an adjunct to chemotherapy for adults with de novo acute myeloid leukemia. Blood. 1999;94:3694–3701
  24. Schiffer CA, Miller K, Larson RA, Amrein PC, Antin JH, Zani VJ, et al. A double-blind, placebo-controlled trial of pegylated recombinant human megakaryocyte growth and development factor as an adjunct to induction and consolidation therapy for patients with acute myeloid leukemia. Blood. 2000;95:2530–2535
  25. Geissler K, Yin JA, Ganser A, Sanz MA, Szer J, Raghavachar A, et al. Prior and concurrent administration of recombinant human megakaryocyte growth and development factor in patients receiving consolidation chemotherapy for de novo acute myeloid leukemia—A randomized, placebo-controlled, double-blind safety and efficacy study. Ann Hematol. 2003;82:677–683
  26. Wielenga JJ, Vellenga E, Groenewegen A, Sonneveld P, Lowenberg B. Recombinant human interleukin-3 (rH IL-3) in combination with remission induction chemotherapy in patients with relapsed acute myelogenous leukemia (AML): A phase I/II study. Leukemia. 1996;10:43–47
  27. Ellis M, Zwaan F, Hedstrom U, Poynton C, Kristensen J, Jumaa P, et al. Recombinant human interleukin 11 and bacterial infection in patients with [correction of] haematological malignant disease undergoing chemotherapy: a double-blind placebo-controlled randomised trial. Lancet. 2003;361:275–280
  28. Griffin JD, Lowenberg B. Clonogenic cells in acute myeloblastic leukemia. Blood. 1986;68:1185–1195
  29. McCulloch EA, Minden MD, Buick RN, Izaguirre CA. Clonal expansion and progression in acute myeloblastic leukemia. Bull Cancer. 1978;65:443–448
  30. Minden MD, Till JE, McCulloch EA. Proliferative state of blast cell progenitors in acute myeloblastic leukemia (AML). Blood. 1978;52:592–600
  31. Guan Y, Hogge DE. Proliferative status of primitive hematopoietic progenitors from patients with acute myelogenous leukemia (AML). Leukemia. 2000;14:2135–2141
  32. Vellenga E, Young DC, Wagner K, Wiper D, Ostapovicz D, Griffin JD. The effects of GM-CSF and G-CSF in promoting growth of clonogenic cells in acute myeloblastic leukemia. Blood. 1987;69:1771–1776
  33. Miyauchi J, Kelleher CA, Wang C, Minkin S, McCulloch EA. Growth factors influence the sensitivity of leukemic stem cells to cytosine arabinoside in culture. Blood. 1989;73:1272–1278
  34. Cannistra SA, Groshek P, Griffin JD. Granulocyte-macrophage colony-stimulating factor enhances the cytotoxic effects of cytosine arabinoside in acute myeloblastic leukemia and in the myeloid blast crisis phase of chronic myeloid leukemia. Leukemia. 1989;3:328–334
  35. Reuter C, Auf der Landwehr U, Schleyer E, Zuhlsdorf M, Ameling C, Rolf C, et al. Modulation of intracellular metabolism of cytosine arabinoside in acute myeloid leukemia by granulocyte-macrophage colony-stimulating factor. Leukemia. 1994;8:217–225
  36. Bhalla K, Holladay C, Arlin Z, Grant S, Ibrado AM, Jasiok M. Treatment with interleukin-3 plus granulocyte-macrophage colony-stimulating factors improves the selectivity of Ara-C in vitro against acute myeloid leukemia blasts. Blood. 1991;78:2674–2679
  37. Lowenberg B, Suciu S, Archimbaud E, Ossenkoppele G, Verhoef GE, Vellenga E, et al. Use of recombinant GM-CSF during and after remission induction chemotherapy in patients aged 61 years and older with acute myeloid leukemia: final report of AML-11, a phase III randomized study of the Leukemia Cooperative Group of European Organisation for the Research and Treatment of Cancer and the Dutch Belgian Hemato-Oncology Cooperative Group. Blood. 1997;90:2952–2961
  38. Heil G, Chadid L, Hoelzer D, Seipelt G, Mitrou P, Huber C, et al. GM-CSF in a double-blind randomized, placebo controlled trial in therapy of adult patients with de novo acute myeloid leukemia (AML). Leukemia. 1995;9:3–9
  39. Hast R, Hellstrom-Lindberg E, Ohm L, Bjorkholm M, Celsing F, Dahl IM, et al. No benefit from adding GM-CSF to induction chemotherapy in transforming myelodysplastic syndromes: Better outcome in patients with less proliferative disease. Leukemia. 2003;17:1827–1833
  40. Uyl-de Groot CA, Lowenberg B, Vellenga E, Suciu S, Willemze R, Rutten FF. Cost-effectiveness and quality-of-life assessment of GM-CSF as an adjunct to intensive remission induction chemotherapy in elderly patients with acute myeloid leukemia. Br J Haematol. 1998;100:629–636
  41. Rowe JM, Neuberg D, Friedenberg W, Bennett JM, Paietta E, Makary AZ, et al. A phase 3 study of three induction regimens and of priming with GM-CSF in older adults with acute myeloid leukemia: A trial by the Eastern Cooperative Oncology Group. Blood. 2004;103:479–485
  42. Thomas X, Fenaux P, Dombret H, Delair S, Dreyfus F, Tilly H, et al. Granulocyte-macrophage colony-stimulating factor (GM-CSF) to increase efficacy of intensive sequential chemotherapy with etoposide, mitoxantrone and cytarabine (EMA) in previously treated acute myeloid leukemia: A multicenter randomized placebo-controlled trial (EMA91 trial). Leukemia. 1999;13:1214–1220
  43. Lofgren C, Paul C, Astrom M, Hast R, Hedenius M, Lerner R, et al. Granulocyte-macrophage colony-stimulating factor to increase efficacy of mitoxantrone, etoposide and cytarabine in previously untreated elderly patients with acute myeloid leukaemia: A Swedish multicentre randomized trial. Br J Haematol. 2004;124:474–480
  44. Estey EH, Thall PF, Pierce S, Cortes J, Beran M, Kantarjian H, et al. Randomized phase II study of fludarabine + cytosine arabinoside + idarubicin +/− all-trans retinoic acid +/− granulocyte colony-stimulating factor in poor prognosis newly diagnosed acute myeloid leukemia and myelodysplastic syndrome. Blood. 1999;93:2478–2484
  45. Buchner T, Berdel WE, Hiddemann W. Priming with granulocyte colony-stimulating factor—Relation to high-dose cytarabine in acute myeloid leukemia. N Engl J Med. 2004;350:2215–2216
  46. Lowenberg B, van Putten W, Theobald M, Gmur J, Verdonck L, Sonneveld P, et al. Effect of priming with granulocyte colony-stimulating factor on the outcome of chemotherapy for acute myeloid leukemia. N Engl J Med. 2003;349:743–752
  47. Thomas X, Raffoux E, Botton S, Pautas C, Arnaud P, de Revel T, et al. Effect of priming with granulocyte-macrophage colony-stimulating factor in younger adults with newly diagnosed acute myeloid leukemia: A trial by the Acute Leukemia French Association (ALFA) Group. Leukemia. 2007;21:453–461
  48. Witz F, Sadoun A, Perrin MC, Berthou C, Briere J, Cahn JY, et al. A placebo-controlled study of recombinant human granulocyte-macrophage colony-stimulating factor administered during and after induction treatment for de novo acute myelogenous leukemia in elderly patients (Groupe Ouest Est Leucemies Aigues Myeloblastiques (GOELAM)). Blood. 1998;91:2722–2730
  49. Guzman ML, Upchurch D, Grimes B, Howard DS, Rizzieri DA, Luger SM, et al. Expression of tumor-suppressor genes interferon regulatory factor 1 and death-associated protein kinase in primitive acute myelogenous leukemia cells. Blood. 2001;97:2177–2179
  50. Ailles LE, Gerhard B, Hogge DE. Detection and characterization of primitive malignant and normal progenitors in patients with acute myelogenous leukemia using long-term coculture with supportive feeder layers and cytokines. Blood. 1997;90:2555–2564
  51. Guan Y, Gerhard B, Hogge DE. Detection, isolation, and stimulation of quiescent primitive leukemic progenitor cells from patients with acute myeloid leukemia (AML). Blood. 2003;101:3142–3149
  52. Demetri GD, Griffin JD. Granulocyte colony-stimulating factor and its receptor. Blood. 1991;78:2791–2808
  53. Ohno R, Tomonaga M, Ohshima T, Masaoka T, Asou N, Oh H, et al. A randomized controlled study of granulocyte colony stimulating factor after intensive induction and consolidation therapy in patients with acute lymphoblastic leukemia (Japan Adult Leukemia Study Group). Int J Hematol. 1993;58:73–81
  54. Larson RA, Dodge RK, Linker CA, Stone RM, Powell BL, Lee EJ, et al. A randomized controlled trial of filgrastim during remission induction and consolidation chemotherapy for adults with acute lymphoblastic leukemia: CALGB study 9111. Blood. 1998;92:1556–1564
  55. Ottmann OG, Ganser A, Freund M, Heil G, Hiddemann W, Heit W, et al. Simultaneous administration of granulocyte colony-stimulating factor (Filgrastim) and induction chemotherapy in acute lymphoblastic leukemia (A pilot study). Ann Hematol. 1993;67:161–167
  56. Scherrer R, Geissler K, Kyrle PA, Gisslinger H, Jager U, Bettelheim P, et al. Granulocyte colony-stimulating factor (G-CSF) as an adjunct to induction chemotherapy of adult acute lymphoblastic leukemia (ALL). Ann Hematol. 1993;66:283–289
  57. Ottmann OG, Hoelzer D, Gracien E, Ganser A, Kelly K, Reutzel R, et al. Concomitant granulocyte colony-stimulating factor and induction chemoradiotherapy in adult acute lymphoblastic leukemia: A randomized phase III trial. Blood. 1995;86:444–450
  58. Geissler K, Koller E, Hubmann E, Niederwieser D, Hinterberger W, Geissler D, et al. Granulocyte colony-stimulating factor as an adjunct to induction chemotherapy for adult acute lymphoblastic leukemia—A randomized phase-III study. Blood. 1997;90:590–596
  59. Holowiecki J, Giebel S, Krzemien S, Krawczyk-Kulis M, Jagoda K, Kopera M, et al. G-CSF administered in time-sequenced setting during remission induction and consolidation therapy of adult acute lymphoblastic leukemia has beneficial influence on early recovery and possibly improves long-term outcome: A randomized multicenter study. Leuk Lymphoma. 2002;43:315–325
  60. Hofmann WK, Seipelt G, Langenhan S, Reutzel R, Schott D, Schoeffski O, et al. Prospective randomized trial to evaluate two delayed granulocyte colony stimulating factor administration schedules after high-dose cytarabine therapy in adult patients with acute lymphoblastic leukemia. Ann Hematol. 2002;81:570–574
  61. Weiser MA, O’Brien S, Thomas DA, Pierce SA, Lam TP, Kantarjian HM. Comparison of two different schedules of granulocyte-colony-stimulating factor during treatment for acute lymphocytic leukemia with a hyper-CVAD (cyclophosphamide, doxorubicin, vincristine, and dexamethasone) regimen. Cancer. 2002;94:285–291
  62. Bassan R, Battista R, Viero P, Pogliani E, Rossi G, Lambertenghi-Deliliers G, et al. Granulocyte colony-stimulating factor (G-CSF, filgrastim) after or during an intensive remission induction therapy for adult acute lymphoblastic leukaemia: Effects, role of patient pretreatment characteristics, and costs. Leuk Lymphoma. 1997;26:153–161
  63. Kantarjian HM, Estey EH, O’Brien S, Anaissie E, Beran M, Rios MB, et al. Intensive chemotherapy with mitoxantrone and high-dose cytosine arabinoside followed by granulocyte-macrophage colony-stimulating factor in the treatment of patients with acute lymphocytic leukemia. Blood. 1992;79:876–881
  64. Ifrah N, Witz F, Jouet JP, Francois S, Lamy T, Linassier C, et al. Intensive short term therapy with granulocyte-macrophage-colony stimulating factor support, similar to therapy for acute myeloblastic leukemia, does not improve overall results for adults with acute lymphoblastic leukemia (GOELAMS Group). Cancer. 1999;86:1496–1505
  65. Papamichael D, Andrews T, Owen D, Carter M, Amess J, Lister TA, et al. Intensive chemotherapy for adult acute lymphoblastic leukaemia given with or without granulocyte-macrophage colony stimulating factor. Ann Hematol. 1996;73:259–263
  66. Thomas X, Boiron JM, Huguet F, Reman O, Sutton L, Turlure P, et al. Efficacy of granulocyte and granulocyte-macrophage colony-stimulating factors in the induction treatment of adult acute lymphoblastic leukemia: A multicenter randomized study. Hematol J. 2004;5:384–394
  67. Bussel JB, Kuter DJ, George JN, McMillan R, Aledort LM, Conklin GT, et al. AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP. N Engl J Med. 2006;355:1672–1681
  68. Kaushansky K. Lineage-specific hematopoietic growth factors. N Engl J Med. 2006;354:2034–2045
  69. Bennett CL, Stinson TJ, Laver JH, Bishop MR, Godwin JE, Tallman MS. Cost analyses of adjunct colony stimulating factors for acute leukemia: Can they improve clinical decision making. Leuk Lymphoma. 2000;37:65–70
  70. Tsimberidou AM, Giles FJ, Estey E, O’Brien S, Keating MJ, Kantarjian HM. The role of gemtuzumab ozogamicin in acute leukaemia therapy. Br J Haematol. 2006;132:398–409
  71. Rutella S, Bonanno G, Procoli A, Mariotti A, Lucia MB, Contemi AM, et al. Granulocyte colony-stimulating factor enhances the in vitro cytotoxicity of gemtuzumab ozogamicin against acute myeloid leukemia cell lines and primary blast cells. Exp Hematol. 2006;34:54–65

PII: S0037-1963(07)00070-4

doi: 10.1053/j.seminhematol.2007.04.007

Seminars in Hematology
Volume 44, Issue 3 , Pages 183-192 , July 2007