Summary
The present study was designed to determine whether Filgrastim, a neutrophil-specific hematopoietic growth factor, could be administered simultaneously with intensive induction chemotherapy for adult acute lymphoblastic leukemia (ALL). The effect of Filgrastim on the severity of chemotherapy-induced neutropenia, fever, and infections was assessed in 15 patients treated according to the protocol of the German multicenter ALL (GMALL) trial 04/89. Filgrastim (5μg/kg/day) was given concurrently with successive cycles of cyclophosphamide, cytosine-arabinoside (ara-C), 6-mercaptopurine (6MP), prednisone (PRD), intrathecal methotrexate, and prophylactic cranial irradiation. During the study period the median total duration of severe neutropenia (<0.5×109/l) in 13 evaluable patients was 8 days, individual periods of neutropenia typically were short. Infections occurred in six patients; seven patients remained fever-free during treatment with Filgrastim. We conclude that simultaneous treatment with Filgrastim and chemotherapy in this specific setting is feasible and well tolerated. The efficacy of this treatment approach in terms of overall treatment results requires further testing in a randomized trial.
Similar content being viewed by others
References
Bettelheim P, Valent M, 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 77:700–711
Bodey GP, Buckley M, Sathe YS, Freireich EJ (1966) Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia. Ann Intern Med 84:328–340
Büchner T, Hiddemann W, Koenigsmann M, Zühlsdorf M, Wörmann B, Boeckmann A, Freire EA, Innig G, Maschmeyer G, Ludwig WD, Sauerland M-C, 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
Büchner T, Hiddemann W, Wörmann B, Rottmann R, Zühlsdorf M, Maschmeyer G, Heit W, Ludwig W-D, Thiel E, Sauerland M-C (1992) Multiple course chemotherapy and GM-CSF from day minus one until neutrophil recovery versus chemotherapy alone in newly diagnosed AML. Ann Hematol G4:A78 (abstr)
Cannistra SA, DiCarlo J, Groshek P, Kanakura Y, Berg D, Mayer RJ, Griffin JD (1991) Simultaneous administration of granulocyte-macrophage colony-stimulating factor and cytosine arabinoside for the treatment of relapsed acute myeloid leukemia. Leukemia 5:230–238
Clarkson B, Ellis S, Little C, Gee T, Arlin Z, Mertelsmann R, Andreeff M, Kempin S, Koziner B, Chaganti R, Jhanwar S, McKenzie S, Cirrincione C, Gaynor J (1985) Acute lymphoblastic leukemia in adults. Semin Oncol 12:160–179
Davis I, Morstyn G (1991) The role of granulocyte colony-stimulating factor in cancer chemotherapy. Semin Hematol 28:25–33
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
Glaspy JA, Golde DW (1990) Clinical trials of myeloid growth factors. Exp Hematol 18:1137–1141
Hiddemann W, Niederle N, von Pawel J, Gatzemeier U, Macha N, Nowrousian M, Graf M, Gracien E (1992) Treatment of NSCLC with Escalated doses of carboplatin/vindesine followed by rG-CSF versus standard-dose therapy: interim results of a prospective randomized comparison. J Cancer Res Clin Oncol 118:[SuppI] 3–4 (abstract)
Hoelzer D, Gale RP (1987) Acute lymphoblastic leukemia in adults: recent progress, future directions, Semin Hematol 24:27–39
Hoelzer D, Thiel E, Bodenstein H, Plaumann L, Büchner T, Urbanitz D, Koch P, Heimpel H, Engelhardt R, Müller U, Wendt F-C, Sodomann H, Rühl H, Herrmann F, Kaboth H, Dietzfelbinger H, Pralle H, Lunscken C, Hellriegel K-P, Spors S, Nowrousian RM, Fischer J, Fülle H, Mitrou PS, Pfreundschuh M, Görg C, Emmerich B, Queisser W, Meyer P, Labedzki L, Essers U, König H, Mainzer K, Herrmann R, Messerer D, Zwingers T (1984) Intensified therapy in acute lymphoblastic and acute undifferentiated leukemia in adults. Blood 64:36–47
Hoelzer D, Thiel E, Loeffler H, Büchner T, Ganser A, Heil G, Kurrle E, Heimpel H, Koch P, Lipp T, Kaboth W, Kuse R, Küchler R, Sodomann H, Maschmeyer G, Freund M, Diedrich H, von Paleske A, Weh J, Kolb H, Müller U, Bross K, Fuhr G, Gassmann W, Gerecke D, Kress M, Busch FW, Nowrousian RM, Schneider W, Aul C, Rühl H, Bartels H, Harms F, Weiss A, Löffler B, Glöckner W, Fülle H, Pralle H, Ho AD, Bonfert B, Emmerich B, Braumann D, Brenner-Serke M, Planker M, Straif K, Meyer P, Greil R, Petsch S, Görg C, Grüneisen A, Vaupel HA, Bodenstein H, Overkamp F, Schlimock G, Augener W, Ohl S, Nowicki L, Raeth U, Zurborn KH, Neiss A, Messerer D (1987) Teniposide (VM-26) and cytosine arabinoside as consolidation therapy in adult high-risk patients with acute lymphoblastic leukemia. Semin Oncol 14:92–97 [Suppl 1]
Hoelzer D, Thiel E, Loeffler H, Büchner T, Ganser A, Heil G, Koch P, Freund M, Diedrich H, Rühl H, Maschmeyer G, Lipp T, Nowrousian MR, Burkert M, Gerecke D, Pralle H, Müller U, Lunscken C, Fülle H, Ho AD, Küchler R, Busch FW, Schneider W, Görg C, Emmerich B, Braumann D, Vaupel HA, von Paleske A, Bartels H, Neiss A, Messerer D (1988) Prognostic factors in a multicenter study for treatment of acute lymphoblastic leukemia in adults. Blood 71:123–131
Kleine H-D, Wagner U, Poliwoda H, Freund M (1992) Effects of tumor necrosis factor alpha on bone marrow aspirates of patients with acute myelogenous leukemia determined by flow-cytometric cell-cycle analysis. J Cancer Res Clin Oncol 118:56–60
Linker CA, Levitt LJ, O'Donnel M, Ries CA, Link MP, Forman SJ, Farbstein MJ (1987) Improved results of treatment of adult acute lymphoblastic leukemia. Blood 69:1242–1248
Meropol NJ, Miller LL, Korn EL, Braitman LE, MacDermott ML, Schuchter LM (1991) The coadministration of granulocyte colony-stimulating factor and cytotoxic chemotherapy results in severe paradoxical myelosuppression. Blood 78:3a [Suppl 1]
Ohno R, Tomonaga M, Kobayashi T, Kanamaru A, Shirakawa S, Masaoka T, Omine M, Oh H, Nomuro T, Sakai Y, Hirano M, Yokomaku S, Nakayama S, Yoshida Y, Miura AB, Morishima Y, Dohy H, Niho Y, Hamajima N, Takaku F (1990) Effect of granulocyte colony-stimulating factor after intensive induction therapy in relapsed or refractory acute leukemia. N Engl J Med 123:871–877
Scherrer R, Geissler K, Kyrle PA, Gisslinger H, Jäger U, Bettelheim P, Laczika K, Locker G, Scholten C, Sillaber C, Schwarzinger I, Thalhammer F, Lechner K (1993) Granulocyte colony-stimulating factor (G-CSF) as an adjunct to induction chemotherapy of adult lymphoblastic leukemia (ALL). Ann Hematol 66:283–289
Teshima H, Ishikawa J, Kitajama H, Yamagami T, Hiraoka A, Nakamura H, Shibata H, Masaoka T, Takaku F (1969) Clinical effects of recombinant human granulocyte colony-stimulating factor in leukemia patients; a phase I/II study. Exp Hematol 17:853–858
Tsuchiya H, Adachi N, Asou N, Takatsuki K, Matsuda I, Kawana F, Murakami T, Mizutani S, Watanabe M (1991) Responses to granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage CSF in PH1-positive acute lymphoblastic leukemia with myeloid surface markers. Blood 77:411–413
Tsukimoto I, Ohara A, Tanaka M, Tsuchida M, Hanawa Y (1992) Effect of rG-CSF on relapsed acute lymphoblastic leukemia in children. Ann Hematol 64:A81 (abstr)
Weite K, Bonilla MA, Gillio AP, Boone TC, Potter GK, Gabrilove JL, Moore MAS, O'Reilly RJ, Souza LM (1987) Recombinant human granulocyte colony-stimulating factor. Effects on hematopoiesis in normal and cyclophosphamidetreated primates. J Exp Med 165:941–948
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ottmann, O.G., Ganser, A., Freund, M. et al. Simultaneous administration of granulocyte colony-stimulating factor (Filgrastim) and induction chemotherapy in acute lymphoblastic leukemia. Ann Hematol 67, 161–167 (1993). https://doi.org/10.1007/BF01695862
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01695862