National Consensus Guideline on Diagnosis and Management of Congenital Neutropenias
-
Saba Fekrvand
,
Reza Yazdani
,
Samaneh Abdolahzade
,
Parisa Ashournia
,
Aida Askarisarvestani
,
Sima Bahrami
,
Maryam Behfar
,
Zahra Daneshmandi
,
Taher Cheraghi
,
Sepideh Darougar
,
Sarehsadat Ebrahimi
,
Shabnam Eskandarzadeh
,
Narges Eslami
,
Golnaz Eslamian
,
Shahrzad Fallah
,
Ali Haghbin
,
Mehrnaz Mesdaghi
,
Majid Marjani
,
Mohammadreza Modaresi
,
Mahshid Movahedi
,
Mohammamd Nabavi
,
Anahita Razaghian
,
Mahnaz Sadeghi-Shabestari
,
Sahar Seraj
,
Seyedehshabnam Seyedsalehi
,
Alireza Shafiei
,
Reza Shiari
,
Sima Shokri
,
Saman Tavakoli
,
Ahmad Vosughimotlagh
,
Vahid Ziaee
,
Nima Rezaei
Abstract
At present, a national consensus or guideline for diagnosing and managing patients suspected of having severe congenital neutropenia (SCN) is lacking. This consensus is written based on a combination of scientific literature and comments from the expert panel of Iranian immunologists. A group of clinical immunologists reviewed the current consensus, presented their comments at a meeting titled “First Meeting on the Diagnosis of Inborn Errors of Immunity (IEI) by IEI Experts” and agreed on this consensus. This consensus guideline provides recommendations on the diagnosis, antimicrobial prophylaxis, management of clinical manifestations, administration of granulocyte colony-stimulating factor (G-CSF) and hematopoietic stem cell transplantation (HSCT) for patients with SCN.
1. Tangye SG, Al-Herz W, Bousfiha A, Cunningham-Rundles C, Franco JL, Holland SM, et al. Human inborn errors of immunity: 2022 update on the classification from the international union of immunological societies expert committee. Journal of clinical immunology. 2022;42(7):1473-507.
2. Bousfiha A, Moundir A, Tangye SG, Picard C, Jeddane L, Al-Herz W, et al. The 2022 update of IUIS phenotypical classification for human inborn errors of immunity. Journal of clinical immunology. 2022;42(7):1508-20.
3. Donadieu J, Beaupain B, Fenneteau O, Bellanné-Chantelot C. Congenital neutropenia in the era of genomics: classification, diagnosis, and natural history. British Journal of Haematology. 2017;179(4):557-74.
4. Donadieu J, Beaupain B, Mahlaoui N, Bellanné-Chantelot C. Epidemiology of congenital neutropenia. Hematology/Oncology Clinics. 2013;27(1):1-17.
5. Spoor J, Farajifard H, Rezaei N. Congenital neutropenia and primary immunodeficiency diseases. Critical Reviews in Oncology/Hematology. 2019;133:149-62.
6. Klein C. Congenital neutropenia. Stiehm's Immune Deficiencies. 2020:797-812.
7. Lebel A, Yacobovich J, Krasnov T, Koren A, Levin C, Kaplinsky C, et al. Genetic analysis and clinical picture of severe congenital neutropenia in Israel. Pediatric Blood & Cancer. 2015;62(1):103-8.
8. Bartocci A, Laino D, Di Cara G, Verrotti A. Epilepsy in Kostmann syndrome: report of a case and review of the literature. Acta Neurologica Belgica. 2016;116:359-62.
9. Boztug K, Klein C. Genetic etiologies of severe congenital neutropenia. Current opinion in pediatrics. 2011;23(1):21-6.
10. Germeshausen M, Deerberg S, Peter Y, Reimer C, Kratz CP, Ballmaier M. The spectrum of ELANE mutations and their implications in severe congenital and cyclic neutropenia. Human mutation. 2013;34(6):905-14.
11. Donadieu J, Fenneteau O, Beaupain B, Mahlaoui N, Chantelot CB. Congenital neutropenia: diagnosis, molecular bases and patient management. Orphanet journal of rare diseases. 2011;6:1-28.
12. Salehi T, Fazlollahi MR, Maddah M, Nayebpour M, Yazdi MT, Alizadeh Z, et al. Prevention and control of infections in patients with severe congenital neutropenia; a follow up study. Iranian Journal of Allergy, Asthma and Immunology. 2012:51-6.
13. Donadieu J, Boutard P, Bernatowska E, Tchernia G, Couillaud G, Philippe N, et al. A European phase II study of recombinant human granulocyte colony-stimulating factor (lenograstim) in the treatment of severe chronic neutropenia in children. European journal of pediatrics. 1997;156:693-700.
14. Donadieu J, Leblanc T, Meunier BB, Barkaoui M, Fenneteau O, Bertrand Y, et al. Analysis of risk factors for myelodysplasias, leukemias and death from infection among patients with congenital neutropenia. Experience of the French Severe Chronic Neutropenia Study Group. haematologica. 2005;90(1):45-53.
15. Rosenberg PS, Alter BP, Link DC, Stein S, Rodger E, Bolyard AA, et al. Neutrophil elastase mutations and risk of leukaemia in severe congenital neutropenia. British journal of haematology. 2008;140(2):210-3.
16. Yetgin S, Olcay L, Koc A, Germeshausen M. Transformation of severe congenital neutropenia to early acute lymphoblastic leukemia in a patient with HAX1 mutation and without G-CSF administration or receptor mutation. Leukemia. 2008;22(9):1797-.
17. Dror Y. Shwachman‐Diamond syndrome. Pediatric blood & cancer. 2005;45(7):892-901.
18. Schroeder T, Hildebrandt B, Mayatepek E, Germing U, Haas R. A patient with glycogen storage disease type Ib presenting with acute myeloid leukemia (AML) bearing monosomy 7 and translocation t (3; 8)(q26; q24) after 14 years of treatment with granulocyte colony-stimulating factor (G-CSF): a case report. Journal of Medical Case Reports. 2008;2:1-5.
19. Pinsk M, Burzynski J, Yhap M, Fraser RB, Cummings B, Ste-Marie M. Acute myelogenous leukemia and glycogen storage disease 1b. Journal of pediatric hematology/oncology. 2002;24(9):756-8.
20. Beel K, Vandenberghe P. G-CSF receptor (CSF3R) mutations in X-linked neutropenia evolving to acute myeloid leukemia or myelodysplasia. haematologica. 2009;94(10):1449.
21. Ferry C, Ouachee M, Leblanc T, Michel G, Notz-Carrere A, Tabrizi R, et al. Hematopoietic stem cell transplantation in severe congenital neutropenia: experience of the French SCN register. Bone marrow transplantation. 2005;35(1):45-50.
22. Rosenberg PS, Alter BP, Bolyard AA, Bonilla MA, Boxer LA, Cham B, et al. The incidence of leukemia and mortality from sepsis in patients with severe congenital neutropenia receiving long-term G-CSF therapy. Blood. 2006;107(12):4628-35.
23. Zeidler C, Welte K, editors. Hematopoietic growth factors for the treatment of inherited cytopenias. Seminars in hematology; 2007: Elsevier.
24. Welte K, Gabrilove J, Bronchud MH, Platzer E, Morstyn G. Filgrastim (r-metHuG-CSF): the first 10 years. 1996.
25. Fioredda F, Calvillo M, Lanciotti M, Lanza T, Giunti L, Castagnola E, et al. Pegfilgrastim in children with severe congenital neutropenia. Pediatric Blood & Cancer. 2010;54(3):465-7.
26. James R, Kinsey S. The investigation and management of chronic neutropenia in children. Archives of disease in childhood. 2006;91(10):852-8.
27. Cottle TE, Fier CJ, Donadieu J, Kinsey SE, editors. Risk and benefit of treatment of severe chronic neutropenia with granulocyte colony-stimulating factor. Seminars in hematology; 2002: Elsevier.
28. Oshima K, Hanada R, Kobayashi R, Kato K, Nagatoshi Y, Tabuchi K, et al. Hematopoietic stem cell transplantation in patients with severe congenital neutropenia: an analysis of 18 Japanese cases. Pediatric transplantation. 2010;14(5):657-63.
29. Zeidler C, Welte K, Barak Y, Barriga F, Bolyard A, Boxer L, et al. Stem cell transplantation in patients with severe congenital neutropenia without evidence of leukemic transformation. Blood, The Journal of the American Society of Hematology. 2000;95(4):1195-8.
30. Connelly JA, Choi SW, Levine JE. Hematopoietic stem cell transplantation for severe congenital neutropenia. Current opinion in hematology. 2012;19(1):44-51.
31. Choi SW, Levine JE. Indications for hematopoietic cell transplantation for children with severe congenital neutropenia. 2010.
2. Bousfiha A, Moundir A, Tangye SG, Picard C, Jeddane L, Al-Herz W, et al. The 2022 update of IUIS phenotypical classification for human inborn errors of immunity. Journal of clinical immunology. 2022;42(7):1508-20.
3. Donadieu J, Beaupain B, Fenneteau O, Bellanné-Chantelot C. Congenital neutropenia in the era of genomics: classification, diagnosis, and natural history. British Journal of Haematology. 2017;179(4):557-74.
4. Donadieu J, Beaupain B, Mahlaoui N, Bellanné-Chantelot C. Epidemiology of congenital neutropenia. Hematology/Oncology Clinics. 2013;27(1):1-17.
5. Spoor J, Farajifard H, Rezaei N. Congenital neutropenia and primary immunodeficiency diseases. Critical Reviews in Oncology/Hematology. 2019;133:149-62.
6. Klein C. Congenital neutropenia. Stiehm's Immune Deficiencies. 2020:797-812.
7. Lebel A, Yacobovich J, Krasnov T, Koren A, Levin C, Kaplinsky C, et al. Genetic analysis and clinical picture of severe congenital neutropenia in Israel. Pediatric Blood & Cancer. 2015;62(1):103-8.
8. Bartocci A, Laino D, Di Cara G, Verrotti A. Epilepsy in Kostmann syndrome: report of a case and review of the literature. Acta Neurologica Belgica. 2016;116:359-62.
9. Boztug K, Klein C. Genetic etiologies of severe congenital neutropenia. Current opinion in pediatrics. 2011;23(1):21-6.
10. Germeshausen M, Deerberg S, Peter Y, Reimer C, Kratz CP, Ballmaier M. The spectrum of ELANE mutations and their implications in severe congenital and cyclic neutropenia. Human mutation. 2013;34(6):905-14.
11. Donadieu J, Fenneteau O, Beaupain B, Mahlaoui N, Chantelot CB. Congenital neutropenia: diagnosis, molecular bases and patient management. Orphanet journal of rare diseases. 2011;6:1-28.
12. Salehi T, Fazlollahi MR, Maddah M, Nayebpour M, Yazdi MT, Alizadeh Z, et al. Prevention and control of infections in patients with severe congenital neutropenia; a follow up study. Iranian Journal of Allergy, Asthma and Immunology. 2012:51-6.
13. Donadieu J, Boutard P, Bernatowska E, Tchernia G, Couillaud G, Philippe N, et al. A European phase II study of recombinant human granulocyte colony-stimulating factor (lenograstim) in the treatment of severe chronic neutropenia in children. European journal of pediatrics. 1997;156:693-700.
14. Donadieu J, Leblanc T, Meunier BB, Barkaoui M, Fenneteau O, Bertrand Y, et al. Analysis of risk factors for myelodysplasias, leukemias and death from infection among patients with congenital neutropenia. Experience of the French Severe Chronic Neutropenia Study Group. haematologica. 2005;90(1):45-53.
15. Rosenberg PS, Alter BP, Link DC, Stein S, Rodger E, Bolyard AA, et al. Neutrophil elastase mutations and risk of leukaemia in severe congenital neutropenia. British journal of haematology. 2008;140(2):210-3.
16. Yetgin S, Olcay L, Koc A, Germeshausen M. Transformation of severe congenital neutropenia to early acute lymphoblastic leukemia in a patient with HAX1 mutation and without G-CSF administration or receptor mutation. Leukemia. 2008;22(9):1797-.
17. Dror Y. Shwachman‐Diamond syndrome. Pediatric blood & cancer. 2005;45(7):892-901.
18. Schroeder T, Hildebrandt B, Mayatepek E, Germing U, Haas R. A patient with glycogen storage disease type Ib presenting with acute myeloid leukemia (AML) bearing monosomy 7 and translocation t (3; 8)(q26; q24) after 14 years of treatment with granulocyte colony-stimulating factor (G-CSF): a case report. Journal of Medical Case Reports. 2008;2:1-5.
19. Pinsk M, Burzynski J, Yhap M, Fraser RB, Cummings B, Ste-Marie M. Acute myelogenous leukemia and glycogen storage disease 1b. Journal of pediatric hematology/oncology. 2002;24(9):756-8.
20. Beel K, Vandenberghe P. G-CSF receptor (CSF3R) mutations in X-linked neutropenia evolving to acute myeloid leukemia or myelodysplasia. haematologica. 2009;94(10):1449.
21. Ferry C, Ouachee M, Leblanc T, Michel G, Notz-Carrere A, Tabrizi R, et al. Hematopoietic stem cell transplantation in severe congenital neutropenia: experience of the French SCN register. Bone marrow transplantation. 2005;35(1):45-50.
22. Rosenberg PS, Alter BP, Bolyard AA, Bonilla MA, Boxer LA, Cham B, et al. The incidence of leukemia and mortality from sepsis in patients with severe congenital neutropenia receiving long-term G-CSF therapy. Blood. 2006;107(12):4628-35.
23. Zeidler C, Welte K, editors. Hematopoietic growth factors for the treatment of inherited cytopenias. Seminars in hematology; 2007: Elsevier.
24. Welte K, Gabrilove J, Bronchud MH, Platzer E, Morstyn G. Filgrastim (r-metHuG-CSF): the first 10 years. 1996.
25. Fioredda F, Calvillo M, Lanciotti M, Lanza T, Giunti L, Castagnola E, et al. Pegfilgrastim in children with severe congenital neutropenia. Pediatric Blood & Cancer. 2010;54(3):465-7.
26. James R, Kinsey S. The investigation and management of chronic neutropenia in children. Archives of disease in childhood. 2006;91(10):852-8.
27. Cottle TE, Fier CJ, Donadieu J, Kinsey SE, editors. Risk and benefit of treatment of severe chronic neutropenia with granulocyte colony-stimulating factor. Seminars in hematology; 2002: Elsevier.
28. Oshima K, Hanada R, Kobayashi R, Kato K, Nagatoshi Y, Tabuchi K, et al. Hematopoietic stem cell transplantation in patients with severe congenital neutropenia: an analysis of 18 Japanese cases. Pediatric transplantation. 2010;14(5):657-63.
29. Zeidler C, Welte K, Barak Y, Barriga F, Bolyard A, Boxer L, et al. Stem cell transplantation in patients with severe congenital neutropenia without evidence of leukemic transformation. Blood, The Journal of the American Society of Hematology. 2000;95(4):1195-8.
30. Connelly JA, Choi SW, Levine JE. Hematopoietic stem cell transplantation for severe congenital neutropenia. Current opinion in hematology. 2012;19(1):44-51.
31. Choi SW, Levine JE. Indications for hematopoietic cell transplantation for children with severe congenital neutropenia. 2010.
| Issue | Vol 8, No 3 (2025) | |
| Section | Review Article | |
| Keywords | ||
| National Consensus Inborn Errors of Immunity Severe Congenital Neutropenia Management G-CSF HSCT | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Fekrvand S, Yazdani R, Abdolahzade S, Ashournia P, Askarisarvestani A, Bahrami S, Behfar M, Daneshmandi Z, Cheraghi T, Darougar S, Ebrahimi S, Eskandarzadeh S, Eslami N, Eslamian G, Fallah S, Haghbin A, Mesdaghi M, Marjani M, Modaresi M, Movahedi M, Nabavi M, Razaghian A, Sadeghi-Shabestari M, Seraj S, Seyedsalehi S, Shafiei A, Shiari R, Shokri S, Tavakoli S, Vosughimotlagh A, Ziaee V, Rezaei N. National Consensus Guideline on Diagnosis and Management of Congenital Neutropenias. Immunol Genet J. 2025;8(3).
