Abstract
Granulocyte colony-stimulating factor (CSF) and granulocyte–macrophage CSF are potent drugs used to increase neutrophil counts after myelosuppressive chemotherapy. However, in various indications, the use of CSFs has no clinical benefit with regard to morbidity or mortality from infectious complications, frequency of antibiotic use, or rate of hospitalization. Thus, the application of CSFs should be limited to indications with proven clinical benefits or evidence of cost-effectiveness. This review will provide an overview of the state-of-the-art use of CSFs in chemotherapy-associated neutropenia, transplantation, and bone marrow failure syndromes. In addition, recently developed drugs for accelerated hematopoietic recovery will be presented.
Similar content being viewed by others
References
Rahman Z, Esparza-Guerra L, Yap HY, Fraschini G, Bodey G, Hortobagyi G (1997) Chemotherapy-induced neutropenia and fever in patients with metastatic breast carcinoma receiving salvage chemotherapy. Cancer 79:1150–1157
Demetri GD, Griffin JD (1991) Granulocyte colony-stimulating factor and its receptor. Blood 78:2791–2808
Duhrsen U, Villeval JL, Boyd J, Kannourakis G, Morstyn G, Metcalf D (1988) Effects of recombinant human granulocyte colony-stimulating factor on hematopoietic progenitor cells in cancer patients. Blood 72:2074–2081
Kitagawa S, Yuo A, Souza LM, Saito M, Miura Y, Takaku F (1987) Recombinant human granulocyte colony-stimulating factor enhances superoxide release in human granulocytes stimulated by the chemotactic peptide. Biochem Biophys Res Commun 144:1143–1146
Lieschke GJ, Grail D, Hodgson G et al (1994) Mice lacking granulocyte colony-stimulating factor have chronic neutropenia, granulocyte and macrophage progenitor cell deficiency, and impaired neutrophil mobilization. Blood 84:1737–1746
Hoglund M (1998) Glycosylated and non-glycosylated recombinant human granulocyte colony-stimulating factor (rhG-CSF)—what is the difference? Med Oncol 15:229–233
Dranoff G, Crawford AD, Sadelain M et al (1994) Involvement of granulocyte–macrophage colony-stimulating factor in pulmonary homeostasis. Science 264:713–716
Milkovich G, Moleski RJ, Reitan JF et al (2000) Comparative safety of filgrastim versus sargramostim in patients receiving myelosuppressive chemotherapy. Pharmacotherapy 20:1432–1440
Hovgaard D, Schifter S, Rabol A, Mortensen BT, Nissen NI (1992) In vivo kinetics of 111indium-labelled autologous granulocytes following i.v. administration of granulocyte–macrophage colony-stimulating factor (GM-CSF). Eur J Haematol 48:202–207
Dorr RT (1993) Clinical properties of yeast-derived versus Escherichia coli-derived granulocyte–macrophage colony-stimulating factor. Clin Ther 15:19–29
Ozer H, Armitage JO, Bennett CL et al (2000) 2000 Update of recommendations for the use of hematopoietic colony-stimulating factors: evidence-based, clinical practice guidelines. American society of clinical oncology growth factors expert panel. J Clin Oncol 18:3558–3585
Dale DC, Bonilla MA, Davis MW et al (1993) A randomized controlled phase III trial of recombinant human granulocyte colony-stimulating factor (filgrastim) for treatment of severe chronic neutropenia. Blood 81:2496–2502
Falzetti F, Aversa F, Minelli O, Tabilio A (1999) Spontaneous rupture of spleen during peripheral blood stem-cell mobilisation in a healthy donor. Lancet 353:555
Balaguer H, Galmes A, Ventayol G, Bargay J, Besalduch J (2004) Splenic rupture after granulocyte-colony-stimulating factor mobilization in a peripheral blood progenitor cell donor. Transfusion 44:1260–1261
Jain KK (1996) Sweet’s syndrome associated with granulocyte colony-stimulating factor. Cutis 57:107–110
McMullin MF, Finch MB (1995) Felty’s syndrome treated with rhG-CSF associated with flare of arthritis and skin rash. Clin Rheumatol 14:204–208
Snowden JA, Biggs JC, Milliken ST et al (1998) A randomised, blinded, placebo-controlled, dose escalation study of the tolerability and efficacy of filgrastim for haemopoietic stem cell mobilisation in patients with severe active rheumatoid arthritis. Bone Marrow Transplant 22:1035–1041
Abboud M, Laver J, Blau CA (1998) Granulocytosis causing sickle-cell crisis. Lancet 351:959
Adler BK, Salzman DE, Carabasi MH, Vaughan WP, Reddy VV, Prchal JT (2001) Fatal sickle cell crisis after granulocyte colony-stimulating factor administration. Blood 97:3313–3314
Rini B, Wadhwa M, Bird C, Small E, Gaines-Das R, Thorpe R (2005) Kinetics of development and characteristics of antibodies induced in cancer patients against yeast expressed rDNA derived granulocyte macrophage colony stimulating factor (GM-CSF). Cytokine 29:56–66
Gribben JG, Devereux S, Thomas NS et al (1990) Development of antibodies to unprotected glycosylation sites on recombinant human GM-CSF. Lancet 335:434–437
Kojima S, Ohara A, Tsuchida M et al (2002) Risk factors for evolution of acquired aplastic anemia into myelodysplastic syndrome and acute myeloid leukemia after immunosuppressive therapy in children. Blood 100:786–790
Ohara A, Kojima S, Hamajima N et al (1997) Myelodysplastic syndrome and acute myelogenous leukemia as a late clonal complication in children with acquired aplastic anemia. Blood 90:1009–1013
Kaito K, Kobayashi M, Katayama T et al (1998) Long-term administration of G-CSF for aplastic anaemia is closely related to the early evolution of monosomy 7 MDS in adults. Br J Haematol 103:297–303
Lyman, GH, Kuderer, NM, Djulbegovic, B (2002) Prophylactic granulocyte colony-stimulating factor in patients receiving dose-intensive cancer chemotherapy: a meta-analysis. Am J Med 112: 406–411
Bohlius J, Reiser M, Schwarzer G, Engert A (2003) Impact of granulocyte colony-stimulating factor (CSF) and granulocyte–macrophage CSF in patients with malignant lymphoma: a systematic review. Br J Haematol 122:413–423
Bohlius J, Reiser M, Schwarzer G, Engert A (2004) Granulopoiesis-stimulating factors to prevent adverse effects in the treatment of malignant lymphoma. Cochrane Database Syst Rev (3):CD003189
Lyman GH, Lyman CG, Sanderson RA, Balducci L (1993) Decision analysis of hematopoietic growth factor use in patients receiving cancer chemotherapy. J Natl Cancer Inst 85:488–493
Lyman GH, Kuderer N, Greene J, Balducci L (1998) The economics of febrile neutropenia: implications for the use of colony-stimulating factors. Eur J Cancer 34:1857–1864
Cosler LE, Calhoun EA, Agboola O, Lyman GH (2004) Effects of indirect and additional direct costs on the risk threshold for prophylaxis with colony-stimulating factors in patients at risk for severe neutropenia from cancer chemotherapy. Pharmacotherapy 24:488–494
Morrison VA, Picozzi V, Scott S et al (2001) The impact of age on delivered dose intensity and hospitalizations for febrile neutropenia in patients with intermediate-grade non-Hodgkin’s lymphoma receiving initial CHOP chemotherapy: a risk factor analysis. Clin Lymphoma 2:47–56
Chrischilles E, Delgado DJ, Stolshek BS, Lawless G, Fridman M, Carter WB (2002) Impact of age and colony-stimulating factor use on hospital length of stay for febrile neutropenia in CHOP-treated non-Hodgkin’s lymphoma. Cancer Control 9:203–211
Repetto L, Biganzoli L, Koehne CH et al (2003) EORTC cancer in the elderly task force guidelines for the use of colony-stimulating factors in elderly patients with cancer. Eur J Cancer 39:2264–2272
Ardizzoni A, Favaretto A, Boni L et al (2005) Platinum–etoposide chemotherapy in elderly patients with small-cell lung cancer: results of a randomized multicenter phase II study assessing attenuated-dose or full-dose with lenograstim prophylaxis—a Forza Operativa Nazionale Italiana Carcinoma Polmonare and Gruppo Studio Tumori Polmonari Veneto (FONICAP–GSTPV) study. J Clin Oncol 23:569–575
Phillips KA, Tannock IF (1998) Design and interpretation of clinical trials that evaluate agents that may offer protection from the toxic effects of cancer chemotherapy. J Clin Oncol 16:3179–3190
Fossa SD, Kaye SB, Mead GM et al (1998) Filgrastim during combination chemotherapy of patients with poor-prognosis metastatic germ cell malignancy. European Organization for Research and Treatment of Cancer, Genito-Urinary Group, and the Medical Research Council Testicular Cancer Working Party, Cambridge, United Kingdom. J Clin Oncol 16:716–724
Savarese DM, Hsieh C, Stewart FM (1997) Clinical impact of chemotherapy dose escalation in patients with hematologic malignancies and solid tumors. J Clin Oncol 15:2981–2995
Rodenhuis S, Richel DJ, van der Wall E et al (1998) Randomised trial of high-dose chemotherapy and haemopoietic progenitor-cell support in operable breast cancer with extensive axillary lymph-node involvement. Lancet 352:515–521
Stadtmauer EA, O’Neill A, Goldstein LJ et al (2000) Conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer. Philadelphia bone marrow transplant group. N Engl J Med 342:1069–1076
Chrystal K, Cheong K, Harper P (2004) Chemotherapy of small cell lung cancer: state of the art. Curr Opin Oncol 16:136–140
Pfreundschuh M, Trumper L, Kloess M et al (2004) Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of elderly patients with aggressive lymphomas: results of the NHL-B2 trial of the DSHNHL. Blood 104:634–641
Pfreundschuh M, Trumper L, Kloess M et al (2004) Two-weekly or 3-weekly CHOP chemotherapy with or without etoposide for the treatment of young patients with good-prognosis (normal LDH) aggressive lymphomas: results of the NHL-B1 trial of the DSHNHL. Blood 104:626–633
Kinoshita T, Hotta T, Tobinai K et al (2004) A randomized controlled trial investigating the survival benefit of dose-intensified multidrug combination chemotherapy (LSG9) for intermediate- or high-grade non-Hodgkin’s lymphoma: Japan clinical oncology group study 9002. Int J Hematol 80:341–350
Citron ML, Berry DA, Cirrincione C et al (2003) Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol 21:1431–1439
Berghmans T, Paesmans M, Lafitte JJ et al (2002) Therapeutic use of granulocyte and granulocyte–macrophage colony-stimulating factors in febrile neutropenic cancer patients. A systematic review of the literature with meta-analysis. Support Care Cancer 10:181–188
Klastersky J, Paesmans M, Rubenstein EB et al (2000) The Multinational Association for Supportive Care in Cancer risk index: a multinational scoring system for identifying low-risk febrile neutropenic cancer patients. J Clin Oncol 18:3038–3051
Talcott JA, Siegel RD, Finberg R, Goldman L (1992) Risk assessment in cancer patients with fever and neutropenia: a prospective, two-center validation of a prediction rule. J Clin Oncol 10:316–322
Hartmann LC, Tschetter LK, Habermann TM et al (1997) Granulocyte colony-stimulating factor in severe chemotherapy-induced afebrile neutropenia. N Engl J Med 336:1776–1780
Holmes FA, O’Shaughnessy JA, Vukelja S et al (2002) Blinded, randomized, multicenter study to evaluate single administration pegfilgrastim once per cycle versus daily filgrastim as an adjunct to chemotherapy in patients with high-risk stage II or stage III/IV breast cancer. J Clin Oncol 20:727–731
Green MD, Koelbl H, Baselga J et al (2003) A randomized double-blind multicenter phase III study of fixed-dose single-administration pegfilgrastim versus daily filgrastim in patients receiving myelosuppressive chemotherapy. Ann Oncol 14:29–35
Vogel CL, Wojtukiewicz MZ, Carroll RR et al (2005) First and subsequent cycle use of pegfilgrastim prevents febrile neutropenia in patients with breast cancer: a multicenter, double-blind, placebo-controlled phase III study. J Clin Oncol 23:1178–1184
Dombret H, Chastang C, Fenaux P et al (1995) 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 332:1678–1683
Rowe JM, Andersen JW, Mazza JJ et al (1995) 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 86:457–462
Stone RM, Berg DT, George SL et al (1995) 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 332:1671–1677
Zittoun R, Suciu S, Mandelli F et al (1996) 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 14:2150–2159
Heil G, Hoelzer D, Sanz MA et al (1997) 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 90:4710–4718
Lowenberg B, Boogaerts MA, Daenen SM et al (1997) Value of different modalities of granulocyte–macrophage colony-stimulating factor applied during or after induction therapy of acute myeloid leukemia. J Clin Oncol 15:3496–3506
Lowenberg B, Suciu S, Archimbaud E et al (1997) 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 90:2952–2961
Godwin JE, Kopecky KJ, Head DR et al (1998) 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 91:3607–3615
Witz F, Sadoun A, Perrin MC et al (1998) 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 91:2722–2730
Usuki K, Urabe A, Masaoka T et al (2002) Efficacy of granulocyte colony-stimulating factor in the treatment of acute myelogenous leukaemia: a multicentre randomized study. Br J Haematol 116:103–112
Schiffer CA (1996) Hematopoietic growth factors as adjuncts to the treatment of acute myeloid leukemia. Blood 88:3675–3685
Harousseau JL, Witz B, Lioure B et al (2000) 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 18:780–787
Pagliuca A, Carrington PA, Pettengell R, Tule S, Keidan J (2003) Guidelines on the use of colony-stimulating factors in haematological malignancies. Br J Haematol 123:22–33
Miyauchi J, Kelleher CA, Wang C, Minkin S, McCulloch EA (1989) Growth factors influence the sensitivity of leukemic stem cells to cytosine arabinoside in culture. Blood 73:1272–1278
Cannistra SA, Groshek P, Griffin JD (1989) 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 3:328–334
Ohno R, Naoe T, Kanamaru A et al (1994) A double-blind controlled study of granulocyte colony-stimulating factor started two days before induction chemotherapy in refractory acute myeloid leukemia. Kohseisho Leukemia Study Group. Blood 83:2086–2092
Hansen PB, Johnsen HE, Jensen L, Gaarsdal E, Simonsen K, Ralfkiaer E (1995) Priming and treatment with molgramostim (rhGM-CSF) in adult high-risk acute myeloid leukemia during induction chemotherapy: a prospective, randomized pilot study. Eur J Haematol 54:296–303
Uyl-de Groot CA, Lowenberg B, Vellenga E, Suciu S, Willemze R, Rutten FF (1998) 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 100:629–636
Thomas X, Fenaux P, Dombret H et al (1999) 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 13:1214–1220
Heil G, Chadid L, Hoelzer D et al (1995) GM-CSF in a double-blind randomized, placebo controlled trial in therapy of adult patients with de novo acute myeloid leukemia (AML). Leukemia 9:3–9
Lowenberg B, van Putten W, Theobald M et al (2003) Effect of priming with granulocyte colony-stimulating factor on the outcome of chemotherapy for acute myeloid leukemia. N Engl J Med 349:743–752
Willemze R, van der Lely N, Zwierzina H et al (1992) A randomized phase-I/II multicenter study of recombinant human granulocyte–macrophage colony-stimulating factor (GM-CSF) therapy for patients with myelodysplastic syndromes and a relatively low risk of acute leukemia. EORTC leukemia cooperative group. Ann Hematol 64:173–180
Vadhan-Raj S, Keating M, LeMaistre A et al (1987) Effects of recombinant human granulocyte–macrophage colony-stimulating factor in patients with myelodysplastic syndromes. N Engl J Med 317:1545–1552
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
Negrin RS, Haeuber DH, Nagler A et al (1989) Treatment of myelodysplastic syndromes with recombinant human granulocyte colony-stimulating factor. A phase I–II trial. Ann Intern Med 110:976–984
Negrin RS, Haeuber DH, Nagler A et al (1990) Maintenance treatment of patients with myelodysplastic syndromes using recombinant human granulocyte colony-stimulating factor. Blood 76:36–43
Ganser A, Volkers 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
Ossenkoppele GJ, van der Holt B, Verhoef GE et al (1999) A randomized study of granulocyte colony-stimulating factor applied during and after chemotherapy in patients with poor risk myelodysplastic syndromes: a report from the HOVON Cooperative Group. Dutch–Belgian Hemato-Oncology Cooperative Group. Leukemia 13:1207–1213
Bernasconi C, Alessandrino EP, Bernasconi P et al (1998) Randomized clinical study comparing aggressive chemotherapy with or without G-CSF support for high-risk myelodysplastic syndromes or secondary acute myeloid leukaemia evolving from MDS. Br J Haematol 102:678–683
Greenberg P, Taylor K, Larson R et al (1993) Phase III randomized multicenter trial of G-CSF vs. observation for myelodysplastic syndromes (MDS). Proc Am Soc Hematol 82:196a (abstr 768)
Negrin RS, Stein R, Vardiman J et al (1993) Treatment of the anemia of myelodysplastic syndromes using recombinant human granulocyte colony-stimulating factor in combination with erythropoietin. Blood 82:737–743
Negrin, RS, Stein, R, Doherty, K et al (1996) Maintenance treatment of the anemia of myelodysplastic syndromes with recombinant human granulocyte colony-stimulating factor and erythropoietin: evidence for in vivo synergy. Blood 87:4076–4081
Hellstrom-Lindberg E, Ahlgren T, Beguin Y et al (1998) Treatment of anemia in myelodysplastic syndromes with granulocyte colony-stimulating factor plus erythropoietin: results from a randomized phase II study and long-term follow-up of 71 patients. Blood 92:68–75
Ottmann OG, Hoelzer D, Gracien E et al (1995) Concomitant granulocyte colony-stimulating factor and induction chemoradiotherapy in adult acute lymphoblastic leukemia: a randomized phase III trial. Blood 86:444–450
Welte K, Reiter A, Mempel K et al (1996) A randomized phase-III study of the efficacy of granulocyte colony-stimulating factor in children with high-risk acute lymphoblastic leukemia. Berlin–Frankfurt–Munster Study Group. Blood 87:3143–3150
Geissler K, Koller E, Hubmann E et al (1997) Granulocyte colony-stimulating factor as an adjunct to induction chemotherapy for adult acute lymphoblastic leukemia—a randomized phase-III study. Blood 90:590–596
Pui CH, Boyett JM, Hughes WT et al (1997) Human granulocyte colony-stimulating factor after induction chemotherapy in children with acute lymphoblastic leukemia. N Engl J Med 336:1781–1787
Larson RA, Dodge RK, Linker CA et al (1998) A randomized controlled trial of filgrastim during remission induction and consolidation chemotherapy for adults with acute lymphoblastic leukemia: CALGB study 9111. Blood 92:1556–1564
Clarke V, Dunstan FD, Webb DK (1999) Granulocyte colony-stimulating factor ameliorates toxicity of intensification chemotherapy for acute lymphoblastic leukemia. Med Pediatr Oncol 32:331–335
Heath JA, Steinherz PG, Altman A et al (2003) Human granulocyte colony-stimulating factor in children with high-risk acute lymphoblastic leukemia: a children’s cancer group study. J Clin Oncol 21:1612–1617
Relling MV, Boyett JM, Blanco JG et al (2003) Granulocyte colony-stimulating factor and the risk of secondary myeloid malignancy after etoposide treatment. Blood 101:3862–3867
Saven A, Burian C, Koziol JA, Piro LD (1998) Long-term follow-up of patients with hairy cell leukemia after cladribine treatment. Blood 92:1918–1926
Chao NJ, Schriber JR, Grimes K et al (1993) Granulocyte colony-stimulating factor “mobilized” peripheral blood progenitor cells accelerate granulocyte and platelet recovery after high-dose chemotherapy. Blood 81:2031–2035
Bishop MR, Anderson JR, Jackson JD et al (1994) High-dose therapy and peripheral blood progenitor cell transplantation: effects of recombinant human granulocyte–macrophage colony-stimulating factor on the autograft. Blood 83:610–616
Lamy T, Drenou B, Grulois I et al (1994) Improvement of hematologic recovery after high-dose intensification using peripheral blood progenitor cells (PBPC) mobilized by chemotherapy and GM-CSF. Ann Hematol 69:297–302
Nademanee A, Sniecinski I, Schmidt GM et al (1994) High-dose therapy followed by autologous peripheral-blood stem-cell transplantation for patients with Hodgkin’s disease and non-Hodgkin’s lymphoma using unprimed and granulocyte colony-stimulating factor-mobilized peripheral-blood stem cells. J Clin Oncol 12:2176–2186
Schmitz N, Linch DC, Dreger P et al (1996) Randomised trial of filgrastim-mobilised peripheral blood progenitor cell transplantation versus autologous bone-marrow transplantation in lymphoma patients. Lancet 347:353–357
Blaise D, Kuentz M, Fortanier C et al (2000) Randomized trial of bone marrow versus lenograstim-primed blood cell allogeneic transplantation in patients with early-stage leukemia: a report from the Societe Francaise de Greffe de Moelle. J Clin Oncol 18:537–546
Bensinger WI, Martin PJ, Storer B et al (2001) Transplantation of bone marrow as compared with peripheral-blood cells from HLA-identical relatives in patients with hematologic cancers. N Engl J Med 344:175–181
Schmitz N, Bacigalupo A, Hasenclever D et al (1998) Allogeneic bone marrow transplantation vs filgrastim-mobilised peripheral blood progenitor cell transplantation in patients with early leukaemia: first results of a randomised multicentre trial of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant 21:995–1003
Hohaus S, Martin H, Wassmann B et al (1998) Recombinant human granulocyte and granulocyte–macrophage colony-stimulating factor (G-CSF and GM-CSF) administered following cytotoxic chemotherapy have a similar ability to mobilize peripheral blood stem cells. Bone Marrow Transplant 22:625–630
Arora M, Burns LJ, Barker JN et al (2004) Randomized comparison of granulocyte colony-stimulating factor versus granulocyte–macrophage colony-stimulating factor plus intensive chemotherapy for peripheral blood stem cell mobilization and autologous transplantation in multiple myeloma. Biol Blood Marrow Transplant 10:395–404
Schmitz N, Dreger P, Zander AR et al (1995) Results of a randomised, controlled, multicentre study of recombinant human granulocyte colony-stimulating factor (filgrastim) in patients with Hodgkin’s disease and non-Hodgkin’s lymphoma undergoing autologous bone marrow transplantation. Bone Marrow Transplant 15:261–266
Klumpp TR, Mangan KF, Goldberg SL, Pearlman ES, Macdonald JS (1995) Granulocyte colony-stimulating factor accelerates neutrophil engraftment following peripheral-blood stem-cell transplantation: a prospective, randomized trial. J Clin Oncol 13:1323–1327
Nemunaitis J, Rosenfeld CS, Ash R et al (1995) Phase III randomized, double-blind placebo-controlled trial of rhGM-CSF following allogeneic bone marrow transplantation. Bone Marrow Transplant 15:949–954
Lee SJ, Weller E, Alyea EP, Ritz J, Soiffer RJ (1998) Efficacy and costs of granulocyte colony-stimulating factor in allogeneic T-cell depleted bone marrow transplantation. Blood 92:2725–2729
Bolwell BJ, Pohlman B, Andresen S et al (1998) Delayed G-CSF after autologous progenitor cell transplantation: a prospective randomized trial. Bone Marrow Transplant 21:369–373
Ciernik IF, Schanz U, Gmur J (1999) Delaying treatment with granulocyte colony-stimulating factor after allogeneic bone marrow transplantation for hematological malignancies: a prospective randomized trial. Bone Marrow Transplant 24:147–151
Bence-Bruckler I, Bredeson C, Atkins H et al (1998) A randomized trial of granulocyte colony-stimulating factor (Neupogen) starting day 1 vs day 7 post-autologous stem cell transplantation. Bone Marrow Transplant 22:965–969
Schleuning M, Thoedtmann R, Josten K, Baurmann H, Schwerdtfeger R (2005) The impact of post transplant use of G-CSF on event free survival in AML patients undergoing allogeneic stem cell transplantation from unrelated donors and in vivo T-cell depletion with ATG. J Clin Oncol 2004 ASCO Annu Meet Proc 22:Abstr 6637
Kumar M, Alter BP (1998) Hematopoietic growth factors for the treatment of aplastic anemia. Curr Opin Hematol 5:226–234
Gluckman E, Rokicka-Milewska R, Hann I et al (2002) Results and follow-up of a phase III randomized study of recombinant human-granulocyte stimulating factor as support for immunosuppressive therapy in patients with severe aplastic anaemia. Br J Haematol 119:1075–1082
Bessho M, Hirashima K, Asano S et al (1997) Treatment of the anemia of aplastic anemia patients with recombinant human erythropoietin in combination with granulocyte colony-stimulating factor: a multicenter randomized controlled study. Multicenter Study Group. Eur J Haematol 58:265–272
Rackoff WR, Orazi A, Robinson CA et al (1996) Prolonged administration of granulocyte colony-stimulating factor (filgrastim) to patients with Fanconi anemia: a pilot study. Blood 88:1588–1593
Scagni P, Saracco P, Timeus F et al (1998) Use of recombinant granulocyte colony-stimulating factor in Fanconi’s anemia. Haematologica 83:432–437
Bonilla MA, Gillio AP, Ruggeiro M et al (1989) Effects of recombinant human granulocyte colony-stimulating factor on neutropenia in patients with congenital agranulocytosis. N Engl J Med 320:1574–1580
Welte K, Zeidler C, Reiter A et al (1990) Differential effects of granulocyte–macrophage colony-stimulating factor and granulocyte colony-stimulating factor in children with severe congenital neutropenia. Blood 75:1056–1063
Boxer LA, Hutchinson R, Emerson S (1992) Recombinant human granulocyte-colony-stimulating factor in the treatment of patients with neutropenia. Clin Immunol Immunopathol 62:S39–S46
Ganser A, Ottmann OG, Erdmann H, Schulz G, Hoelzer D (1989) The effect of recombinant human granulocyte–macrophage colony-stimulating factor on neutropenia and related morbidity in chronic severe neutropenia. Ann Intern Med 111:887–892
Dale DC, Cottle TE, Fier CJ et al (2003) Severe chronic neutropenia: treatment and follow-up of patients in the Severe Chronic Neutropenia International Registry. Am J Hematol 72:82–93
Leary AG, Yang YC, Clark SC, Gasson JC, Golde DW, Ogawa M (1987) Recombinant gibbon interleukin 3 supports formation of human multilineage colonies and blast cell colonies in culture: comparison with recombinant human granulocyte–macrophage colony-stimulating factor. Blood 70:1343–1348
Ganser A, Seipelt G, Lindemann A et al (1990) Effects of recombinant human interleukin-3 in patients with myelodysplastic syndromes. Blood 76:455–462
Ganser A, Lindemann A, Seipelt G et al (1990) Effects of recombinant human interleukin-3 in patients with normal hematopoiesis and in patients with bone marrow failure. Blood 76:666–676
Nemunaitis J, Appelbaum FR, Singer JW et al (1993) Phase I trial with recombinant human interleukin-3 in patients with lymphoma undergoing autologous bone marrow transplantation. Blood 82:3273–3278
Lindemann A, Ganser A, Herrmann F et al (1991) Biologic effects of recombinant human interleukin-3 in vivo. J Clin Oncol 9:2120–2127
Hofstra LS, Kristensen GB, Willemse PH et al (1998) Randomized trial of recombinant human interleukin-3 versus placebo in prevention of bone marrow depression during first-line chemotherapy for ovarian carcinoma. J Clin Oncol 16:3335–3344
Ganser A, Lindemann A, Ottmann OG et al (1992) Sequential in vivo treatment with two recombinant human hematopoietic growth factors (interleukin-3 and granulocyte–macrophage colony-stimulating factor) as a new therapeutic modality to stimulate hematopoiesis: results of a phase I study. Blood 79:2583–2591
Nabholtz JM, Cantin J, Chang J et al (2002) Phase III trial comparing granulocyte colony-stimulating factor to leridistim in the prevention of neutropenic complications in breast cancer patients treated with docetaxel/doxorubicin/cyclophosphamide: results of the BCIRG 004 trial. Clin Breast Cancer 3:268–275
Farese AM, Smith WG, Giri JG, Siegel N, McKearn JP, MacVittie TJ (2001) Promegapoietin-1a, an engineered chimeric IL-3 and Mpl-L receptor agonist, stimulates hematopoietic recovery in conventional and abbreviated schedules following radiation-induced myelosuppression in nonhuman primates. Stem Cells 19:329–338
Broxmeyer HE, Lu L, Cooper S, Ruggieri L, Li ZH, Lyman SD (1995) Flt3 ligand stimulates/costimulates the growth of myeloid stem/progenitor cells. Exp Hematol 23:1121–1129
Zhang S, Fukuda S, Lee Y et al (2000) Essential role of signal transducer and activator of transcription (Stat)5a but not Stat5b for Flt3-dependent signaling. J Exp Med 192:719–728
Molineux G, McCrea C, Yan XQ, Kerzic P, McNiece I (1997) Flt-3 ligand synergizes with granulocyte colony-stimulating factor to increase neutrophil numbers and to mobilize peripheral blood stem cells with long-term repopulating potential. Blood 89:3998–4004
Fleming WH, Mulcahy JM, McKearn JP, Streeter PR (2001) Progenipoietin-1: a multifunctional agonist of the granulocyte colony-stimulating factor receptor and fetal liver tyrosine kinase-3 is a potent mobilizer of hematopoietic stem cells. Exp Hematol 29:943–951
Freedman RS, Vadhan-Raj S, Butts C et al (2003) Pilot study of Flt3 ligand comparing intraperitoneal with subcutaneous routes on hematologic and immunologic responses in patients with peritoneal carcinomatosis and mesotheliomas. Clin Cancer Res 9:5228–5237
Nabholtz JM, Falkson C, Campos D et al (2003) Docetaxel and doxorubicin compared with doxorubicin and cyclophosphamide as first-line chemotherapy for metastatic breast cancer: results of a randomized, multicenter, phase III trial. J Clin Oncol 21:968–975
Biganzoli L, Cufer T, Bruning P et al (2002) Doxorubicin and paclitaxel versus doxorubicin and cyclophosphamide as first-line chemotherapy in metastatic breast cancer: the European organization for research and treatment of cancer 10961 multicenter phase III trial. J Clin Oncol 20:3114–3121
Meluch AA, Greco FA, Gray JR et al (2003) Preoperative therapy with concurrent paclitaxel/carboplatin/infusional 5-FU and radiation therapy in locoregional esophageal cancer: final results of a minnie pearl cancer research network phase II trial. Cancer J 9:251–260
Sternberg CN, De Mulder PH, Schornagel JH et al (2001) Randomized phase III trial of high-dose-intensity methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) chemotherapy and recombinant human granulocyte colony-stimulating factor versus classic MVAC in advanced urothelial tract tumors: European organization for research and treatment of cancer protocol no. 30924. J Clin Oncol 19:2638–2646
Vaughn DJ, Malkowicz SB, Zoltick B et al (1998) Paclitaxel plus carboplatin in advanced carcinoma of the urothelium: an active and tolerable outpatient regimen. J Clin Oncol 16:255–260
Rose PG, Blessing JA, Gershenson DM, McGehee R (1999) Paclitaxel and cisplatin as first-line therapy in recurrent or advanced squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol 17:2676–2680
Shin DM, Glisson BS, Khuri FR et al (1998) Phase II trial of paclitaxel, ifosfamide, and cisplatin in patients with recurrent head and neck squamous cell carcinoma. J Clin Oncol 16:1325–1330
von Pawel J, Schiller JH, Shepherd FA et al (1999) Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol 17:658–667
Velasquez WS, Cabanillas F, Salvador P et al (1988) Effective salvage therapy for lymphoma with cisplatin in combination with high-dose Ara-C and dexamethasone (DHAP). Blood 71:117–122
Velasquez WS, McLaughlin P, Tucker S et al (1994) ESHAP—an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study. J Clin Oncol 12:1169–1176
Kewalramani T, Zelenetz AD, Nimer SD et al (2004) Rituximab and ICE as second-line therapy before autologous stem cell transplantation for relapsed or primary refractory diffuse large B-cell lymphoma. Blood 103:3684–3688
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Heuser, M., Ganser, A. Colony-stimulating factors in the management of neutropenia and its complications. Ann Hematol 84, 697–708 (2005). https://doi.org/10.1007/s00277-005-1087-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00277-005-1087-4