Summary
The introduction of hematopoietic growth factors into the management of leukemia can influence the outcome of treatment in several ways, depending on the sensitivity and the response of normal and leukemic cells. In this paper we report on the effects of the administration ofEscherichia coli-produced, human recombinant granulocyte-macrophage colony-stimulating factor (GMCSF) in 15 adult patients with acute nonlymphocytic leukemia (ANLL) resistant to first-line treatment or in relapse. GM-CSF was given at a dose of 5–10 μg/kg/day as a 6-h i.v. infusion, prior to chemotherapy (CHT) (for 7 days) and after CHT (until evidence of failure or of remission). In the pre-CHT period there was a clear trend towards an increase of circulating neutrophils (PMN) and/or blast cell count (median 0.3 vs. 1.0×109/l for PMN, and 0.5 vs. 2.3 for blast cells). After chemotherapy, in the patients who achieved complete remission (CR), the median time to a PMN count > 0.5×109/l and > 1×109/l was 16 days (range 13–27) and 19 days (range 13–42) respectively. The outcome of treatment was CR for 8/15 (53%), death during induction for 3/15 (20%), and failure for 4/15 (27%). All failures occurred in patients with an increase of blast cell count during pre-CHT GM-CSF administration. Toxicity and side effects were minor, apart from an acute respiratory syndrome that developed twice in the same patient, at doses of 10 and 3 μg/kg/day. These data suggest that investigation of GM-CSF in the treatment of ANLL is worth pursuing, with special attention to GM-CSF effects prior to chemotherapy.
Similar content being viewed by others
References
Antin JH, Smith BR, Holmes W, Rosenthal DS (1988) Phase I/II study of recombinant human granulocyte-macrophage colony-stimulating factor in aplastic anemia and myelodysplastic syndrome. Blood 72: 705–713
Appelbaum FR (1989) The clinical use of hematopoietic growth factors. Semin Hematol 26 [Suppl 3]: 7–14
Barlogie B, Jagannath S, Dixon DO, Cheson B, Smallwood L, Hendrickson A, Purvis JD, Bonnern E, Alexanian R (1990) Highdose melphalan and granulocyte-macrophage colony-stimulating factor for refractory multiple myeloma. Blood 76: 677–680
Bennet JM, Catovsky D, Daniel MT, Flandrin G, Galton DAG, Gralnick HR, Sultan C (1985) Proposed revised criteria for the classification of acute myeloid leukemia. Ann Intern Med 103: 626–633
Blazar BR, Kersey JH, McGlave PB, Vallera DA, Lasky LC, Haake RJ, Bostrom B, Weisdorf DR, Epstein C, Ramsay NKC (1989) In vivo administration of recombinant human granulocyte/macrophage colony-stimulating factor in acute lymphoblastic leukemia patients receiving purged autografts. Blood 73: 849–857
Brandt SJ, Peters WP, Atwater SK, Kurtzberg J, Borowitz MJ, Jones RB, Shipall EJ, Bast RC, Gilbert CJ, Oette DH (1988) Effect of recombinant human granulocyte-macrophage colonystimulating factor on hematopoietic reconstitution after highdose chemotherapy and autologous bone marrow transplantation. N Engl J Med 318: 869–876
Budel LM, Touw IP, Delwel R, Lowenberg B (1989) Granulocyte colony-stimulating factor receptors in human acute myelocytic leukemia. Blood 74: 2268–2273
Buechner T, Hiddemann W, Koenigsmann M, Zuehlsdorf M, Woermann B, Boeckmann A, Aguion-Freire E, Innig G, Maschmeyer G, Ludwig WD, Sauerland CM, Schulz G (1990) Recombinant human GM-CSF following chemotherapy (CT) versus chemotherapy alone in patients with high-risk AML. Blood 76 [Suppl 1]: 135 a (abstract)
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: 694–699
Delwel R, Salem M, Pellens C, Dorssers L, Wagemaker G, Clark S, Lowenberg B (1988) Growth regulation of human acute myeloid leukemia: effects of five recombinant hematopoietic factors in a serum-free culture system. Blood 72: 1944–1949
Dexter TM (1989) Regulation of hemopoietic cell growth and development: experimental and clinical studies. Leukemia 3: 469–474
Estey EH, Dixon D, Kantarjian HM, Keating MJ, McCredie K, Bodey GP, Kurzrock R, Talpaz M, Freireich EJ, Deisseroth AB, Gutterman JU (1990) Treatment of poor-prognosis, newly diagnosed acute myeloid leukemia with Ara-C and recombinant human granulocyte-macrophage colony-stimulating factor. Blood 75: 1766–1769
Estey E, McCredie K, Keating MJ, Kantarjian HM, Kurzrock R, Talpaz M, Gutterman JU, Deisseroth AB (1990) Treatment of acute myelogenous leukemia with chemotherapy and hematopoietic growth factors. Cancer Bull 42: 156–162
Estey E, Kantarjian H, Keating M, Deisseroth A, Gutterman J, Plunkett W (1990) Use of GM-CSF prior to chemotherapy of AML: effects on circulating blast count, thymidine incorporation and Ara-CTP formation. Blood 76 [Suppl 1]: 142a (abstract)
Ganser A, Voelkers B, Greher J, Ottmann OG, Walther F, Becher R, Bergmann L, Schulz G, Hoelzer D (1989) Recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes — a phase I/II trial. Blood 73: 31–37
Gianni AM, Siena S, Bregni M, Tarella C, Stern AC, Pileri A, Bonadonna G (1989) Granulocyte-macrophage colony-stimulating factor to harvest circulating haemopoietic stem cells for autotransplantation. Lancet I: 580–584
Goldstone A, Gribben J, McMillan A (1990) The role of growth factors in bone-marrow transplantation. Leuk Lymphoma 1: 87–93
Groopman JE, Molina JM, Scadden DT (1989) Hematopoietic growth factors. N Engl J Med 321: 1449–1459
Ho AD, Del Valle F, Engelhard M, Hiddemann W, Rueckle H, Schlimok G, Haas R, Thiel E, Andreesen R, Fiedler W, Frisch J, Schulz G, Hunstein W (1990) Mitoxantrone/high-dose-Ara-C and recombinant human GM-CSF in the treatment of refractory non-Hodgkin's lymphoma. Cancer 66: 423–430
Lacombe F, Dumain P, Puntous M, Marit G, Cony-Makhoul P, Belloc F, Laurent G, Bernard Ph, Boisseau MR, Reiffers J (1990) Clinical and biological results in AML patients treated with GM-CSF and intensive chemotherapy. Blood 76 [Suppl 1]: 292a (abstract)
Laver J, Moore MAS (1989) Clinical use of recombinant human hematopoietic growth factors. JNCI 81: 1370–1382
Lieschke GJ, Maher D, Cebon J, O'Connor M, Green M, Sheridan W, Boyd A, Ralling M, Bonnern E, Metcalf D, Burgess AW, McGrath K, Fox RM, Morstyn G (1989) Effects of bacterially synthesized recombinant human granulocyte-macrophage colony-stimulating factor in patients with advanced malignancy. Ann Intern Med 110: 357–364
McCulloch EA, Minden MD, Miyauchi J, Kelleher CA, Wang C (1988) Stem cell renewal and differentiation in acute myeloblastic leukemia. J Cell Sci [Suppl] 10: 267–281
Motoji T, Takanashi M, Fuchinoue M, Masuda M, Oshimi K, Mizoguchi H (1989) Effect of recombinant GM-CSF and recombinant G-CSF on colony formation of blast progenitors in acute myeloblastic leukemia. Exp Hematol 17: 56–60
Negrin RS, Haeuber DH, Nagler A, Olds LC, Donlon T, Souza LM, Greenberg PL (1989) Treatment of myelodysplastic syndromes with recombinant human granulocyte colony-stimulating factor. Ann Intern Med 110: 976–984
Ohno R, Tomonaga M, Kobayashi T, Kanamaru A, Shirakawa S, Masaoka T, Omine M, Oh H, Nomura T, Sakai Y, Hirano M, Yokomaku S, Nakayama S, Yoshida Y, Miura AB, Morishima Y, Dohy H, Niho Y, Hamajima N, Takaku F (1990) Intensive induction therapy in relapsed or refractory acute leukemia. N Engl J Med 323: 871–877
Platzer E (1989) Human hemopoietic growth factors. Eur J Haematol 42: 1–15
Tafuri A, Estev E, Valent P, Bettelheim P, Godfrey L, Chen R, Redner A, Deisseroth A, Andreeff M (1990) Cell kinetic effects in vivo of rhGM-CSF as pre-induction treatment in acute myeloblastic leukemia. Blood 76 [Suppl 1]: 168a (abstract)
Teshima H, Ishikawa J, Kitayama H, Yamagami T, Hiraoka A, Nakamura H, Shibata H, Masaoka T, Takaku F (1989) Clinical effects of recombinant human granulocyte colony-stimulating factor in leukemia patients: a phase I/II study. Exp Hematol 17: 853–858
Visani G, Tosi P, Gamberi B, Cenacchi A, Mazzanti P, Stabilini C, Bandini G, Mazza P, Gherlinzoni F, Cavo M, Tura S (1990) Accelerated hemopoietic recovery after chemotherapy and autologous bone marrow transplantation in hematological malignancies using recombinant GM-CSF: preliminary results obtained in 14 cases. Haematologica 75: 551–554
Author information
Authors and Affiliations
Additional information
Work supported by MURST (grant 40%–60%) and by CNR
Rights and permissions
About this article
Cite this article
Visani, G., Damiani, D., Cenacchi, A. et al. Granulocyte-macrophage colony-stimulating factor in acute non-lymphocytic leukemia before and after chemotherapy. Ann Hematol 63, 276–281 (1991). https://doi.org/10.1007/BF01698378
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01698378