Myeloid growth factors have been used for more than 20 years to ameliorate myelotoxicity after cancer chemotherapy and to prevent infections in patients with chronic neutropenia. Almost all data on long-term outcomes come from studies of granulocyte colony-stimulating factor (G-CSF). This article focuses on the long-term benefits and risks associated with G-CSF therapy, including data for other myeloid factors, as available.
Dr. Lyman has disclosed that he receives research support from Amgen, Inc. Dr. Dale has disclosed that he receives research support from and is a consultant for Amgen, Inc. Several of the large meta-analyses discussed in this manuscript were conducted by the ANC Study Group, which is supported in part by research grant support to Duke University from Amgen, Inc.
Kuderer NM, Dale DC, Crawford J et al.. Impact of primary prophylaxis with granulocyte colony-stimulating factor on febrile neutropenia and mortality in adult cancer patients receiving chemotherapy: a systematic review. J Clin Oncol 2007;25:3158–3167.
Wittman B, Horan J, Lyman GH. Prophylactic colony-stimulating factors in children receiving myelosuppressive chemotherapy: a meta-analysis of randomized controlled trials. Cancer Treat Rev 2006;32:289–303.
Aapro MS, Bohlius J, Cameron DA et al.. 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer 2011;47:8–32.
- Search Google Scholar
- Export Citation
. Aapro MS Bohlius J Cameron DA 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer 2011; 47: 8– 32.
Crawford J, Armitage J, Balducci L et al.. NCCN Clinical Practice Guidelines in Oncology for Myeloid Growth Factors. J Natl Compr Canc Netw 2009;7:64–83.
Smith TJ, Khatcheressian J, Lyman GH 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.
Preisler HD, Lyman GH. Acute myelogenous leukemia subsequent to therapy for a different neoplasm: clinical features and response to therapy. Am J Hematol 1977;3:209–218.
Crump M, Tu D, Shepherd L et al.. Risk of acute leukemia following epirubicin-based adjuvant chemotherapy: a report from the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol 2003;21:3066–3071.
Kalaycio M, Rybicki L, Pohlman B et al.. Risk factors before autologous stem-cell transplantation for lymphoma predict for secondary myelodysplasia and acute myelogenous leukemia. J Clin Oncol 2006;24:3604–3610.
Le Deley MC, Suzan F, Cutuli B et al.. Anthracyclines, mitoxantrone, radiotherapy, and granulocyte colony-stimulating factor: risk factors for leukemia and myelodysplastic syndrome after breast cancer. J Clin Oncol 2007;25:292–300.
Leone G, Pagano L, Ben-Yehuda D et al.. Therapy-related leukemia and myelodysplasia: susceptibility and incidence. Haematologica 2007;92:1389–1398.
Patt DA, Duan Z, Fang S et al.. Acute myeloid leukemia after adjuvant breast cancer therapy in older women: understanding risk. J Clin Oncol 2007;25:3871–3876.
Praga C, Bergh J, Bliss J et al.. Risk of acute myeloid leukemia and myelodysplastic syndrome in trials of adjuvant epirubicin for early breast cancer: correlation with doses of epirubicin and cyclophosphamide. J Clin Oncol 2005; 23:4179–4191.
Hershman D, Neugut AI, Jacobson JS et al.. Acute myeloid leukemia or myelodysplastic syndrome following use of granulocyte colony-stimulating factors during breast cancer adjuvant chemotherapy. J Natl Cancer Inst 2007;99:196–205.
Relling MV, Boyett JM, Blanco JG et al.. Granulocyte colony-stimulating factor and the risk of secondary myeloid malignancy after etoposide treatment. Blood 2003;101:3862–3867.
Lyman GH, Dale DC, Wolff DA et al.. Acute myeloid leukemia or myelodysplastic syndrome in randomized controlled clinical trials of cancer chemotherapy with granulocyte colony-stimulating factor: a systematic review. J Clin Oncol 2010;28:2914–2924.
Clark OA, Lyman GH, Castro AA et al.. Colony-stimulating factors for chemotherapy-induced febrile neutropenia: a meta-analysis of randomized controlled trials. J Clin Oncol 2005;23:4198–4214.
Horwitz M, Benson KF, Person RE et al.. Mutations in ELA2, encoding neutrophil elastase, define a 21-day biological clock in cyclic haematopoiesis. Nat Genetics 1999;23:433–436.
Dale DC, Person RE, Bolyard AA et al.. Mutations in the gene encoding neutrophil elastase in congenital and cyclic neutropenia. Blood 2000;96:2317–2322.
Klein C, Grudzien M, Appaswamy G et al.. HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease). Nat Genet 2007;39:86–92.
Papadaki HA, Pontikoglou C. Pathophysiologic mechanisms, clinical features and treatment of idiopathic neutropenia. Expert Rev Hematol 2008;12:217–229.
Jakubowski AA, Souza L, Kelly F et al.. Effects of human granulocyte colony-stimulating factor in a patient with idiopathic neutropenia. N Engl J Med 1989;320:38–42.
Hammond WP, Price TH, Souza LM, Dale DC. Treatment of cyclic neutropenia with granulocyte colony stimulating factor. N Engl J Med 1989;320:1306–1311.
Bonilla MA, Gillio AP, Ruggeiro M et al.. Effects of recombinant human granulocyte colony-stimulating factor on neutropenia in patients with congenital agranulocytosis. N Engl J Med 1989;320:1574–1580.
Welte K, Zeidler C, Reiter A et al.. Differential effects of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor in children with severe congenital neutropenia. Blood 1990;75:1056–1063.
Imashuku S, Tsuchida M, Sasaki M et al.. Recombinant human granulocyte-colony-stimulating factor in the treatment of patients with chronic benign granulocytopenia and congenital agranulocytosis (Kostmann's syndrome). Acta Paediatr 1992;81:133–136.
Dale DC, Bonilla MA, Davis MW et al.. A randomized controlled phase III trial of recombinant human granulocyte colony-stimulating factor (filgrastim) for treatment of severe chronic neutropenia. Blood 1993;81:2496–2502.
Dale DC, Cottle TE, Fier CJ et al.. Severe chronic neutropenia: treatment and follow-up of patients in the Severe Chronic Neutropenia International Registry. Am J Hematol 2003;72:82–93.
Dale DC, Bolyard AA, Schwinzer BG et al.. The Severe Chronic Neutropenia International Registry: 10-year follow-up report. Support Cancer Ther 2006;3:220–231.
Wright DG, Kenney RF, Oette DH et al.. Contrasting effects of recombinant human granulocyte-macrophage colony-stimulating factor (CSF) and granulocyte CSF treatment on the cycling of blood elements in childhood-onset cyclic neutropenia. Blood 1994;84:1257–1267.
Mori PG, Pasino M, Dufour C et al.. Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and rhG-CSF in the treatment of a child with severe chronic neutropenia. Blood 1994;84:3244–3245.
Jones E, Bolyard AA, Dale DC. Quality of life in patients receiving granulocyte colony stimulating factor for treatment of severe chronic neutropenia. JAMA 1993;270:1132–1133.
Rosenberg PS, Alter BP, Bolyard AA et al.. Severe Chronic Neutropenia International Registry. The incidence of leukemia and mortality from sepsis in patients with severe congenital neutropenia receiving long-term G-CSF therapy. Blood 2006;107:4628–4635.
Rosenberg PS, Zeidler C, Bolyard AA et al.. Stable long-term risk of leukaemia in patients with severe congenital neutropenia maintained on G-CSF therapy. Br J Haematol 2010;150:196–199.
Rosenberg PS, Alter BP, Link DC et al.. Neutrophil elastase mutations and risk of leukaemia in severe congenital neutropenia. Br J Haematol 2008;140:210–213.
DiMeglio LA, Bolyard AA, Marrero TM et al.. The risk of low bone mineral density with long-term G-CSF therapy for severe chronic neutropenia [abstract]. Blood 2010;16:Abstract 634.
Boxer LA, Bolyard AA, Marrero TM et al.. Outcomes of pregnancies for women with severe chronic neutropenia with or without G-CSF treatment [abstract]. Blood 2010;16:635–636.
Choi SW, Boxer LA, Pulsipher MA et al.. Stem cell transplantation in patients with severe congenital neutropenia with evidence of leukemic transformation. Bone Marrow Transplant 2005;35:473–477.
Carlsson G, Winiarski J, Ljungman P et al.. Hematopoietic stem cell transplantation in severe congenital neutropenia. Pediatr Blood Cancer 2011;56:444–451.