Advertisement

Neonatology pp 1561-1573 | Cite as

Recombinant G-CSF Treatment of Severe Chronic Neutropenia in Neonates and Infants

  • Robert D. Christensen
Reference work entry

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.

References

  1. Águeda S, Rocha G, Ferreira F et al (2012) Neonatal alloimmune neutropenia: still a diagnostic and therapeutical challenge. J Pediatr Hematol Oncol 34:497–499CrossRefGoogle Scholar
  2. 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 21:1061–1065CrossRefGoogle Scholar
  3. Angelis D, Kubicky RA, Zubrow AB (2015) Methimazole associated neutropenia in a preterm neonate treated for hyperthyroidism. Case Rep Endocrinol 2015:680191Google Scholar
  4. Aprikyan AA, Carlsson G, Stein S et al (2004) Neutrophil elastase mutations in severe congenital neutropenia patients of the original Kostmann family. Blood 103:389CrossRefGoogle Scholar
  5. 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–F176CrossRefGoogle Scholar
  6. 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 103:4119–4125CrossRefGoogle Scholar
  7. Bernstein HM, Pollock BH, Calhoun DA, Christensen RD (2001) Administration of recombinant G-CSF to neonates with septicemia: a meta-analysis. Pediatrics 138:917–920CrossRefGoogle Scholar
  8. 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 107:36–41CrossRefGoogle Scholar
  9. 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 3:64–68Google Scholar
  10. 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 5:215–220CrossRefGoogle Scholar
  11. Bux J, Behrens G, Jaeger G, Welte K (1998) Diagnosis and clinical course of autoimmune neutropenia in infancy; analysis of 240 cases. Blood 91:181–186PubMedGoogle Scholar
  12. 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 86:2509–2515PubMedGoogle Scholar
  13. 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 134:64–70CrossRefGoogle Scholar
  14. Calhoun DA, Christensen RD (1997) The occurrence of Kostmann syndrome in preterm neonates. Pediatrics 99:259–261CrossRefGoogle Scholar
  15. Carlsson G, Fasth A (2001) Infantile genetic agranulocytosis, morbus Kostmann: presentation of six cases from the original “Kostmann family” and a review. Acta Paediatr 90:757–764CrossRefGoogle Scholar
  16. Carr R (2000) Neutrophil production and function in newborn infants. Br J Haematol 110:18–28CrossRefGoogle Scholar
  17. Carr R, Huizinga TWJ (2000) Low sFcRIII demonstrates reduced neutrophil reserves in preterm neonates. Arch Dis Child Fetal Neonatal Ed 83:F160CrossRefGoogle Scholar
  18. Carr R, Modi N (1997) Haemopoietic colony stimulating factors for preterm neonates. Arch Dis Child 76:F128–F133CrossRefGoogle Scholar
  19. Carr R, Modi N (2004) Haemopoietic growth factors for neonates: assessing risks and benefits. Acta Paediatr Suppl 93:15–19CrossRefGoogle Scholar
  20. 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 103:796–802CrossRefGoogle Scholar
  21. Carr R, Modi N, Dore C (2003) G-CSF and GM-CSF for treating or preventing neonatal infections. Cochrane Database Syst Rev CD003066Google Scholar
  22. 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 373:226–233CrossRefGoogle Scholar
  23. 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 1:202–206CrossRefGoogle Scholar
  24. Chow JY (2001) The molecular basis of type I glycogen storage diseases. Curr Mol Med 1:25–44CrossRefGoogle Scholar
  25. Christensen RD, Calhoun DA (2004) Congenital neutropenia. Clin Perinatol 31:29–38CrossRefGoogle Scholar
  26. Christensen RD, Henry E, Wiedmeier SE et al (2006) Neutropenia among extremely low birth-weight neonates: data from a multihospital healthcare system. J Perinatol 26:682–687CrossRefGoogle Scholar
  27. Christensen RD, Yoder BA, Baer VL et al (2015) Early-onset neutropenia in small for gestational age infants. Pediatrics 136:e1259–1267CrossRefGoogle Scholar
  28. Clarke SL, Bowron A, Gonzalez IL et al (2013) Barth syndrome. Orphanet J Rare Dis 12(8):23CrossRefGoogle Scholar
  29. Conway LT, Clay ME, Kline WE et al (1987) Natural history of primary autoimmune neutropenia in infancy. Pediatrics 79:728–733PubMedGoogle Scholar
  30. Crahes M, Saugier-Veber P, Patrier S et al (2013) Foetal presentation of cartilage hair hypoplasia with extensive granulomatous inflammation. Eur J Med Genet 56:365–370CrossRefGoogle Scholar
  31. 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 45:1308–1313CrossRefGoogle Scholar
  32. Dale DC, Welte K (2011) Cyclic and chronic neutropenia. Cancer Treat Res 157:97–108CrossRefGoogle Scholar
  33. Davoren A, Saving K, McFarland JG et al (2004) Neonatal neutropenia and bacterial sepsis associated with placental transfer of maternal neutrophil-specific autoantibodies. Transfusion 44:1041–1046CrossRefGoogle Scholar
  34. 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 157:583–588CrossRefGoogle Scholar
  35. Fujiu T, Maruyama K, Koizumi T (2002) Early-onset group B streptococcal sepsis in a preterm infant with Kostmann syndrome. Acta Paediatr 91:1397–1399CrossRefGoogle Scholar
  36. 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 58:12–18CrossRefGoogle Scholar
  37. 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 84:1427–1433PubMedGoogle Scholar
  38. Guiddir T, Frémond ML, Triki TB et al (2014) Anti-TNF-α therapy may cause neonatal neutropenia. Pediatrics 134:e1189–e1193CrossRefGoogle Scholar
  39. Henry E, Christensen RD (2015) Reference intervals in neonatal hematology. Clin Perinatol. doi:10.1016/j.cip.2015/04/005CrossRefPubMedGoogle Scholar
  40. 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 27:19–41CrossRefGoogle Scholar
  41. Hutter JJ Jr, Hathaway WE, Wayne ER (1976) Hematologic abnormalities in severe neonatal necrotizing enterocolitis. J Pediatr 88:1026–1031CrossRefGoogle Scholar
  42. 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 23:493–497CrossRefGoogle Scholar
  43. Juul SE, Calhoun DA, Christensen RD (1998) “Idiopathic neutropenia” in very low birthweight infants. Acta Paediatr 87:963–968CrossRefGoogle Scholar
  44. 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 21:469–474PubMedGoogle Scholar
  45. Kimberlin DW, Jester PM, Sánchez PJ et al (2015) Valganciclovir for symptomatic congenital cytomegalovirus disease. N Engl J Med 372:933–943CrossRefGoogle Scholar
  46. Kling PJ, Hutter JJ (2003) Hematologic abnormalities in severe neonatal necrotizing enterocolitis: 25 years later. J Perinatol 23:523–530CrossRefGoogle Scholar
  47. Koenig JM, Christensen RD (1989a) Incidence, neutrophil kinetics, and natural history of neonatal neutropenia associated with maternal hypertension. N Engl J Med 321:557–562CrossRefGoogle Scholar
  48. Koenig JM, Christensen RD (1989b) Neutropenia and thrombocytopenia in infants with Rh hemolytic disease. J Pediatr 114:625–631CrossRefGoogle Scholar
  49. 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 165:467–473CrossRefGoogle Scholar
  50. Koenig JM, Hunter DD, Christensen RD (1991) Neutropenia in donor (anemic) twins involved in the twin-twin transfusion syndrome. J Perinatol 11:355–358PubMedGoogle Scholar
  51. Kostmann R (1956) Infantile genetic agranulocytosis; agranulocytosis infantilis hereditaria. Acta Paediatr 45(Suppl 105):1–78Google Scholar
  52. 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.e1CrossRefGoogle Scholar
  53. Lekjowski M, Maheshwari A, Calhoun DA et al (2003) Persistent perianal abcess in early infancy as a presentation of autoimmune neutropenia. J Perinatol 23:428–430CrossRefGoogle Scholar
  54. Maheshwari A (2014) Neutropenia in the newborn. Curr Opin Hematol 21:43–49CrossRefGoogle Scholar
  55. Makaryan V, Zeidler C, Bolyard AA et al (2015) The diversity of mutations and clinical outcomes for ELANE-associated neutropenia. Curr Opin Hematol 22:3–11CrossRefGoogle Scholar
  56. 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 95:89–98CrossRefGoogle Scholar
  57. 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–F53CrossRefGoogle Scholar
  58. 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–F326CrossRefGoogle Scholar
  59. 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 168:1069–1074CrossRefGoogle Scholar
  60. Mhaskar R, Clark OA, Lyman G et al (2014) Colony-stimulating factors for chemotherapy-induced febrile neutropenia. Cochrane Database Syst Rev 10:CD003039Google Scholar
  61. 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 107:30–35CrossRefGoogle Scholar
  62. Modi N, Carr R (2000) Promising stratagems for reducing the burden of neonatal sepsis. Arch Dis Child Fetal Neonatal Ed 83:F150–F153CrossRefGoogle Scholar
  63. Mouzinho A, Rosenfeld CR, Sanchez PJ, Risser R (1992) Effect of maternal hypertension on neonatal neutropenia and risk of nosocomial infection. Pediatrics 90:430–435PubMedGoogle Scholar
  64. Myers KC, Davies SM, Shimamura A (2013) Clinical and molecular pathophysiology of Shwachman-Diamond syndrome: an update. Hematol Oncol Clin North Am 27:117–128CrossRefGoogle Scholar
  65. 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 16:11–24CrossRefGoogle Scholar
  66. 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.e1CrossRefGoogle Scholar
  67. 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 23:368–382CrossRefGoogle Scholar
  68. 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 128:135–137CrossRefGoogle Scholar
  69. Saito-Benz M, Miller HE, Berry MJ (2015) Shwachman-Diamond syndrome in a preterm neonate. J Paediatr Child Health. doi:10.1111/jpc.12941CrossRefPubMedGoogle Scholar
  70. 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 102:6–13CrossRefGoogle Scholar
  71. 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 28:275–281CrossRefGoogle Scholar
  72. Sharma G, Nesin M, Feuerstein M, Bussel JB (2009) Maternal and neonatal characteristics associated with neonatal neutropenia in hypertensive pregnancies. Am J Perinatol 26:683–689CrossRefGoogle Scholar
  73. 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):334–340CrossRefGoogle Scholar
  74. 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 34:203–207CrossRefGoogle Scholar
  75. Song R, Subbarao GC, Maheshwari A (2012) Haematological abnormalities in neonatal necrotizing enterocolitis. J Matern Fetal Neonatal Med 25(Suppl 4):22–25PubMedPubMedCentralGoogle Scholar
  76. Tirali RE, Yalçınkaya Erdemci Z, Çehreli SB (2013) Oral findings and clinical implications of patients with congenital neutropenia: a literature review. Turk J Pediatr 55:241–245PubMedGoogle Scholar
  77. 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 135:56–59CrossRefGoogle Scholar
  78. 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.12741CrossRefPubMedGoogle Scholar
  79. 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 35:287–300CrossRefGoogle Scholar
  80. Wiedl C, Walter AW (2010) Granulocyte colony stimulating factor in neonatal alloimmune neutropenia: a possible association with induced thrombocytopenia. Pediatr Blood Cancer 54:1014–1016PubMedGoogle Scholar
  81. 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 144:459–466CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Divisions of Neonatology and Hematology, Department of PediatricsUniversity of Utah School of Medicine, Intermountain HealthcareSalt Lake CityUSA

Personalised recommendations