Abstract
Neutropenia is a condition characterized by a diminution in the number of circulating neutrophils and increases susceptibility to local and systemic infections. Neutropenia can be a transient and benign condition, in which there is no need of specific therapy, except for intercurrent situations, such as antibiotic therapy in infections. Alternatively, it can be part of a more complex and severe situation, associated with other organ dysfunctions or malformations. Severe chronic neutropenia is a group of diagnoses characterized by hyporegenerative neutropenia, generally present from birth; these newborns and children often need the administration of recombinant granulocyte colony-stimulating factor (rG-CSF). The advent of rG-CSF dramatically improved the lives of these patients, elevating their circulating neutrophil concentrations, markedly reducing infectious illnesses, and extending life expectancy. When a transient variety of neonatal neutropenia is diagnosed, distinct from severe chronic neutropenia (SCN), the benefit of rG-CSF treatment is unproven and of dubious value.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Águeda S, Rocha G, Ferreira F et al (2012) Neonatal alloimmune neutropenia: still a diagnostic and therapeutical challenge. J Pediatr Hematol Oncol 34:497–499
Ahmad A, Laborada G, Bussel J, Nesin M (2002) Comparison of recombinant G-CSF, recombinant human GM-CSF and placebo for treatment of septic preterm infants. Pediatr Infect Dis J 21:1061–1065
Angelis D, Kubicky RA, Zubrow AB (2015) Methimazole associated neutropenia in a preterm neonate treated for hyperthyroidism. Case Rep Endocrinol 2015:680191
Aprikyan AA, Carlsson G, Stein S et al (2004) Neutrophil elastase mutations in severe congenital neutropenia patients of the original Kostmann family. Blood 103:389
Bedford-Russell AR, Emmerson AJB, Wilkinson N et al (2001) A trial of recombinant human granulocyte colony stimulating factor for the treatment of very low birthweight infants with presumed sepsis and neutropenia. Arch Dis Child Fetal Neonatal Ed 84:F172–F176
Bellanne-Chantelot C, Clauin S, Leblanc T et al (2004) Mutations in the ELA2 gene correlate with more severe expression of neutropenia: a study of 81 patients from the French Neutropenia Register. Blood 103:4119–4125
Bernstein HM, Pollock BH, Calhoun DA, Christensen RD (2001) Administration of recombinant G-CSF to neonates with septicemia: a meta-analysis. Pediatrics 138:917–920
Bilgin K, Yaramis A, Haspolat K et al (2001) A randomized trial of granulocyte-macrophage colony-stimulating factor in neonates with sepsis and neutropenia. Pediatrics 107:36–41
Borjianyazdi L, Froomandi M, Noori Shadkam M et al (2013) The effect of granulocyte colony stimulating factor administration on preterm infant with neutropenia and clinical sepsis: a randomized clinical trial. Iran J Pediatr Hematol Oncol 3:64–68
Bracho F, Goldman S, Cairo MS (1998) Potential use of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor in neonates. Curr Opin Hematol 5:215–220
Bux J, Behrens G, Jaeger G, Welte K (1998) Diagnosis and clinical course of autoimmune neutropenia in infancy; analysis of 240 cases. Blood 91:181–186
Cairo MS, Christensen RD, Sender LS et al (1995) Results of a phase I/II trial of recombinant human granulocyte-macrophage colony-stimulating factor in very low birthweight neonates: significant induction of circulatory neutrophils, monocytes, platelets, and bone marrow neutrophils. Blood 86:2509–2515
Cairo MS, Agosti J, Ellis R et al (1999) A randomised double-blind placebo-controlled trial of prophylactic recombinant human GM-CSF to reduce nosocomial infection in very low birthweight neonates. J Pediatr 134:64–70
Calhoun DA, Christensen RD (1997) The occurrence of Kostmann syndrome in preterm neonates. Pediatrics 99:259–261
Carlsson G, Fasth A (2001) Infantile genetic agranulocytosis, morbus Kostmann: presentation of six cases from the original “Kostmann family” and a review. Acta Paediatr 90:757–764
Carr R (2000) Neutrophil production and function in newborn infants. Br J Haematol 110:18–28
Carr R, Huizinga TWJ (2000) Low sFcRIII demonstrates reduced neutrophil reserves in preterm neonates. Arch Dis Child Fetal Neonatal Ed 83:F160
Carr R, Modi N (1997) Haemopoietic colony stimulating factors for preterm neonates. Arch Dis Child 76:F128–F133
Carr R, Modi N (2004) Haemopoietic growth factors for neonates: assessing risks and benefits. Acta Paediatr Suppl 93:15–19
Carr R, Modi N, Doré CJ et al (1999) A randomised controlled trial of prophylactic GM-CSF in human newborns less than 32 weeks gestation. Pediatrics 103:796–802
Carr R, Modi N, Dore C (2003) G-CSF and GM-CSF for treating or preventing neonatal infections. Cochrane Database Syst Rev CD003066
Carr R, Brocklehurst P, Doré CJ, Modi N (2009) Granulocyte-macrophage colony stimulating factor administered as prophylaxis for reduction of sepsis in extremely preterm, small for gestational age neonates (the PROGRAMS trial): a single-blind, multicentre, randomised controlled trial. Lancet 373:226–233
Chaudhuri J, Mitra S, Mukhopadhyay D et al (2012) Granulocyte colony-stimulating factor for preterms with sepsis and neutropenia: a randomized controlled trial. J Clin Neonatol 1:202–206
Chow JY (2001) The molecular basis of type I glycogen storage diseases. Curr Mol Med 1:25–44
Christensen RD, Calhoun DA (2004) Congenital neutropenia. Clin Perinatol 31:29–38
Christensen RD, Henry E, Wiedmeier SE et al (2006) Neutropenia among extremely low birth-weight neonates: data from a multihospital healthcare system. J Perinatol 26:682–687
Christensen RD, Yoder BA, Baer VL et al (2015) Early-onset neutropenia in small for gestational age infants. Pediatrics 136:e1259–1267
Clarke SL, Bowron A, Gonzalez IL et al (2013) Barth syndrome. Orphanet J Rare Dis 12(8):23
Conway LT, Clay ME, Kline WE et al (1987) Natural history of primary autoimmune neutropenia in infancy. Pediatrics 79:728–733
Crahes M, Saugier-Veber P, Patrier S et al (2013) Foetal presentation of cartilage hair hypoplasia with extensive granulomatous inflammation. Eur J Med Genet 56:365–370
Curtis BR, Reon C, Aster RH (2005) Neonatal alloimmune neutropenia attributed to maternal immunoglobulin G antibodies against the neutrophil alloantigen HNA1c(SH): a report of five cases. Transfusion 45:1308–1313
Dale DC, Welte K (2011) Cyclic and chronic neutropenia. Cancer Treat Res 157:97–108
Davoren A, Saving K, McFarland JG et al (2004) Neonatal neutropenia and bacterial sepsis associated with placental transfer of maternal neutrophil-specific autoantibodies. Transfusion 44:1041–1046
Drossou-Agakidou V, Kanakoudi-Tsakalidou F, Taparkou A et al (1998) Administration of recombinant human granulocyte-colony stimulating factor to septic neonates induces neutrophilia and enhances the neutrophil respiratory burst and beta2 integrin expression. Results of a randomized controlled trial. Eur J Pediatr 157:583–588
Fujiu T, Maruyama K, Koizumi T (2002) Early-onset group B streptococcal sepsis in a preterm infant with Kostmann syndrome. Acta Paediatr 91:1397–1399
Gathwala G, Walia M, Bala H, Singh S (2012) Recombinant human granulocyte colony-stimulating factor in preterm neonates with sepsis and relative neutropenia: a randomized, single-blind, non-placebo-controlled trial. J Trop Pediatr 58:12–18
Gillan ER, Christensen RD, Suen Y et al (1994) A randomized, placebo-controlled trial of recombinant human granulocyte colony-stimulating factor administration in newborn infants with presumed sepsis: significant induction of peripheral and bone marrow neutrophilia. Blood 84:1427–1433
Guiddir T, Frémond ML, Triki TB et al (2014) Anti-TNF-α therapy may cause neonatal neutropenia. Pediatrics 134:e1189–e1193
Henry E, Christensen RD (2015) Reference intervals in neonatal hematology. Clin Perinatol. doi:10.1016/j.cip.2015/04/005
Horwitz MS, Corey SJ, Grimes HL, Tidwell T (2013) ELANE mutations in cyclic and severe congenital neutropenia: genetics and pathophysiology. Hematol Oncol Clin North Am 27:19–41
Hutter JJ Jr, Hathaway WE, Wayne ER (1976) Hematologic abnormalities in severe neonatal necrotizing enterocolitis. J Pediatr 88:1026–1031
Juul SE, Christensen RD (2003) Effect of recombinant granulocyte colony-stimulating factor on blood neutrophil concentrations among patients with “idiopathic neonatal neutropenia”: a randomized, placebo-controlled trial. J Perinatol 23:493–497
Juul SE, Calhoun DA, Christensen RD (1998) “Idiopathic neutropenia” in very low birthweight infants. Acta Paediatr 87:963–968
Khan TH, Shahidullah M, Mannan MA, Nahar N (2012) Effect of recombinant human granulocyte colony stimulating factor (rhG-CSF) for the treatment of neonates in presumed sepsis with neutropenia. Mymensingh Med J 21:469–474
Kimberlin DW, Jester PM, Sánchez PJ et al (2015) Valganciclovir for symptomatic congenital cytomegalovirus disease. N Engl J Med 372:933–943
Kling PJ, Hutter JJ (2003) Hematologic abnormalities in severe neonatal necrotizing enterocolitis: 25 years later. J Perinatol 23:523–530
Koenig JM, Christensen RD (1989a) Incidence, neutrophil kinetics, and natural history of neonatal neutropenia associated with maternal hypertension. N Engl J Med 321:557–562
Koenig JM, Christensen RD (1989b) Neutropenia and thrombocytopenia in infants with Rh hemolytic disease. J Pediatr 114:625–631
Koenig JM, Christensen RD (1991) The mechanism responsible for diminished neutrophil production in neonates delivered of women with pregnancy-induced hypertension. Am J Obstet Gynecol 165:467–473
Koenig JM, Hunter DD, Christensen RD (1991) Neutropenia in donor (anemic) twins involved in the twin-twin transfusion syndrome. J Perinatol 11:355–358
Kostmann R (1956) Infantile genetic agranulocytosis; agranulocytosis infantilis hereditaria. Acta Paediatr 45(Suppl 105):1–78
Kuhn P, Messer J, Paupe A et al (2009) A multicenter, randomized, placebo-controlled trial of prophylactic recombinant granulocyte-colony stimulating factor in preterm neonates with neutropenia. J Pediatr 155:324–330.e1
Lekjowski M, Maheshwari A, Calhoun DA et al (2003) Persistent perianal abcess in early infancy as a presentation of autoimmune neutropenia. J Perinatol 23:428–430
Maheshwari A (2014) Neutropenia in the newborn. Curr Opin Hematol 21:43–49
Makaryan V, Zeidler C, Bolyard AA et al (2015) The diversity of mutations and clinical outcomes for ELANE-associated neutropenia. Curr Opin Hematol 22:3–11
Manroe BL, Weinberg AG, Rosenfeld CR, Browne R (1979) The neonatal blood count in health and disease. I. Reference values for neutrophilic cells. J Pediatr 95:89–98
Marlow N, Morris T, Brocklehurst P et al (2013) A randomised trial of granulocyte-macrophage colony-stimulating factor for neonatal sepsis: outcomes at 2 years. Arch Dis Child Fetal Neonatal Ed 98:F46–F53
Marlow N, Morris T, Brocklehurst P (2015) A randomised trial of granulocyte-macrophage colony-stimulating factor for neonatal sepsis: childhood outcomes at 5 years. Arch Dis Child Fetal Neonatal Ed 100:F320–F326
Melis D, Della Casa R, Parini R et al (2009) Vitamin E supplementation improves neutropenia and reduces the frequency of infections in patients with glycogen storage disease type 1b. Eur J Pediatr 168:1069–1074
Mhaskar R, Clark OA, Lyman G et al (2014) Colony-stimulating factors for chemotherapy-induced febrile neutropenia. Cochrane Database Syst Rev 10:CD003039
Miura E, Procianoy RS, Bittar C et al (2001) A randomized double-masked, placebo controlled trial of recombinant granulocyte colony-stimulating factor administration to preterm infants with the clinical diagnosis of early-onset sepsis. Pediatrics 107:30–35
Modi N, Carr R (2000) Promising stratagems for reducing the burden of neonatal sepsis. Arch Dis Child Fetal Neonatal Ed 83:F150–F153
Mouzinho A, Rosenfeld CR, Sanchez PJ, Risser R (1992) Effect of maternal hypertension on neonatal neutropenia and risk of nosocomial infection. Pediatrics 90:430–435
Myers KC, Davies SM, Shimamura A (2013) Clinical and molecular pathophysiology of Shwachman-Diamond syndrome: an update. Hematol Oncol Clin North Am 27:117–128
Parravicini E, van de Ven C, Anderson L, Cairo MS (2002) Myeloid hematopoietic growth factors and their role in prevention and/or treatment of neonatal sepsis. Transfus Med Rev 16:11–24
Procianoy RS, Silveira RC, Mussi-Pinhata MM et al (2010) Sepsis and neutropenia in very low birth weight infants delivered of mothers with preeclampsia. J Pediatr 157:434–438, 438.e1
Rogler LE, Kosmyna B, Moskowitz D et al (2014) Small RNAs derived from lncRNA RNase MRP have gene-silencing activity relevant to human cartilage-hair hypoplasia. Hum Mol Genet 23:368–382
Rosenthal J, Healey T, Ellis R et al (1996) A two year follow-up of neonates with presumed sepsis treated with recombinant human G-CSF during the first week of life. J Pediatr 128:135–137
Saito-Benz M, Miller HE, Berry MJ (2015) Shwachman-Diamond syndrome in a preterm neonate. J Paediatr Child Health. doi:10.1111/jpc.12941
Schibler KR, Osborne KA, Leung LY et al (1998) A randomized placebo-controlled trial of granulocyte colony-stimulating factor administration to newborn infants with neutropenia and clinical signs of early-onset sepsis. Pediatrics 102:6–13
Schmutz N, Henry E, Jopling J, Christensen RD (2008) Expected ranges for blood neutrophil concentrations of neonates: the Manroe and Mouzinho charts revisited. J Perinatol 28:275–281
Sharma G, Nesin M, Feuerstein M, Bussel JB (2009) Maternal and neonatal characteristics associated with neonatal neutropenia in hypertensive pregnancies. Am J Perinatol 26:683–689
Shaw BE, Confer DL, Hwang W, Pulsipher MA (2015) A review of the genetic and long-term effects of G-CSF injections in healthy donors: a reassuring lack of evidence for the development of haematological malignancies. Bone Marrow Transplant 50(3):334–340
Shu Z, Li XH, Bai XM et al (2015) Clinical characteristics of severe congenital neutropenia caused by novel ELANE gene mutations. Pediatr Infect Dis J 34:203–207
Song R, Subbarao GC, Maheshwari A (2012) Haematological abnormalities in neonatal necrotizing enterocolitis. J Matern Fetal Neonatal Med 25(Suppl 4):22–25
Tirali RE, Yalçınkaya Erdemci Z, Çehreli SB (2013) Oral findings and clinical implications of patients with congenital neutropenia: a literature review. Turk J Pediatr 55:241–245
Tsao PN, Teng RJ, Tang JR, Yau KI (1999) Granulocyte colony-stimulating factor in the cord blood of premature neonates born to mothers with pregnancy-induced hypertension. J Pediatr 135:56–59
van den Tooren-de Groot R, Ottink M, Huiskes E, van Rossum A et al (2014) Management and outcome of 35 cases with foetal/neonatal alloimmune neutropenia. Acta Paediatr. doi:10.1111/apa.12741
Visser G, de Jager W, Verhagen LP et al (2012) Survival, but not maturation, is affected in neutrophil progenitors from GSD-1b patients. J Inherit Metab Dis 35:287–300
Wiedl C, Walter AW (2010) Granulocyte colony stimulating factor in neonatal alloimmune neutropenia: a possible association with induced thrombocytopenia. Pediatr Blood Cancer 54:1014–1016
Zeidler C, Germeshausen M, Klein C, Welte K (2009) Clinical implications of ELA2-, HAX1-, and G-CSF-receptor (CSD3R) mutations in severe congenital neutropenia. Br J Haematol 144:459–466
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG, part of Springer Nature
About this entry
Cite this entry
Christensen, R.D. (2018). Recombinant G-CSF Treatment of Severe Chronic Neutropenia in Neonates and Infants. In: Buonocore, G., Bracci, R., Weindling, M. (eds) Neonatology. Springer, Cham. https://doi.org/10.1007/978-3-319-29489-6_245
Download citation
DOI: https://doi.org/10.1007/978-3-319-29489-6_245
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-29487-2
Online ISBN: 978-3-319-29489-6
eBook Packages: MedicineReference Module Medicine