Seminars in Hematology
Volume 43, Issue 3 , Pages 189-195 , July 2006

Severe Congenital Neutropenia

  • Karl Welte

      Affiliations

    • Department of Pediatric Hematology/Oncology, Medical School Hannover, Hannover, Germany.
    • Corresponding Author InformationAddress correspondence to Karl Welte, MD, PhD, Department for Pediatric Hematology/Oncology, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
  • ,
  • Cornelia Zeidler

      Affiliations

    • Department of Pediatric Hematology/Oncology, Medical School Hannover, Hannover, Germany.
  • ,
  • David C. Dale

      Affiliations

    • Department of Medicine, University of Washington, Seattle, WA.

References 

  1. Kostmann R . Infantile genetic agranulocytosis . Acta Pediatr Scand . 1956;45:1–78
  2. Kostmann R . Infantile genetic agranulocytosis (A review with presentation of ten new cases) . Acta Pediatr Scand . 1975;64:362–368
  3. Rappeport J , Parkman R , Newburger P , Camitta BM , Chusid MJ . Correction of infantile granulocytosis (Kostmann syndrome) by allogeneic bone marrow transplantation . Am J Med . 1980;68:605–609
  4. Souza L , Boone T , Gabrilove J , Lai PH , Zsebo KM , Murdock DC , et al.  Recombinant human granulocyte colony-stimulating factor (Effects on normal and leukemic myeloid cells) . Science . 1986;232:61–65
  5. Bonilla M , Gillio A , Ruggeiro M , Kernan NA , Brochstein JA , Abboud 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
  6. Bonilla M , Dale D , Zeidler C , Last L , Reiter A , Ruggeiro M , et al.  Long-term safety of treatment with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) in patients with severe congenital neutropenias . Br J Hematol . 1994;88:723–730
  7. Freedman MH . Safety of long-term administration of granulocyte colony-stimulating factor for severe chronic neutropenia . Curr Opin Hematol . 1997;4:217–224
  8. Welte K , Dale D . Pathophysiology and treatment of severe chronic neutropenia . Ann Hematol . 1996;72:158–165
  9. Welte K , Boxer L . Severe chronic neutropenia (Pathophysiology and therapy) . Semin Hematol . 1997;34:267–278
  10. Zeidler C , Boxer L , Dale DC , Freedman MH , Kinsey S , Welte K . Management of Kostmann syndrome in the G-CSF era . Br J Haematol . 2000;109:490–495
  11. Zeidler C , Welte K , Barak Y , Barriga F , Bolyard AA , Boxer L , et al.  Stem cell transplantation in patients with severe congenital neutropenia without evidence of leukemic transformation . Blood . 2000;95:1195–1198
  12. Mempel K , Pietsch T , Menzel  , Zeidler C , Welte K . Increased serum levels of granulocyte colony-stimulating factor in patients with severe congenital neutropenia . Blood . 1991;77:1919–1922
  13. Kyas U , Pietsch T , Welte K . Expression of receptors for granulocyte-colony stimulating factor on neutrtophilsfrom patients with severe congenital neutropenia and cyclic neutropenia . Blood . 1992;79:1144–1147
  14. Horwitz M , Benson KF , Person RE , Aprikyan AG , Dale DC . Mutations in ELA2, encoding neutrophil elastase, define a 21-day biological clock in cyclic haematopoesis . Nat Genet . 1999;23:433–436
  15. Ancliff PJ, Gale RE, Watts MJ, Liesner R, Hann IM, Strobel S, et al. Paternal mosaicism proves the pathogenic nature of mutations in neutrophil elastase in severe congenital neutropenia . Blood . 2002;100:707–709
  16. Dale DC , Liles WC , Grawicz D , Aprikyan AG . Clinical implications of mutations of neutrophil elastase in congenital and cyclic neutropenia . J Pediatr Hematol Oncol . 2001;23:208–210
  17. Donadieu J , Leblanc T , Meunier B , Barkaoui M , Fenneteau O , Bertrand Y , et al.  Analysis of risk factors for myelodysplasia/leukemia and infectious death among patients with congenital neutropenia (Experience of the French Severe Chronic Neutropenia Study Group) . Haematologica . 2005;90:45–53
  18. Dale DC , Person RE , Bolyard AA , Aprikyan AG , Bos C , Bonilla MA , et al.  Mutations in the gene encoding neutrophil elastase in congenital and cyclic neutropenia . Blood . 2000;96:2317–2322
  19. Massullo P , Druhan LJ , Bunnell BA , Hunter MG , Robinson JM , Marsh CB , et al.  Aberrant subcellular targeting of the G185R neutrophil elastase mutant associated with severe congenital neutropenia induces premature apoptosis of differentiating promyelocytes . Blood . 2005;105:3397–3404
  20. Germeshausen M , Schulze H , Ballmaier M , Zeidler C , Welte K . Mutations in the gene encoding neutrophil elastase (ELA2) are not sufficient to cause the phenotype of congenital neutropenia . Br J Haematol . 2001;115:1–4
  21. Koellner I , Sodeik B , Schreek S , Heyn H , von Neuhoff N , Germeshausen M , et al.   Mutations in neutrophil elastase causino congenital neutropenia lead to cytoplasmic protein accumulation and induction of the unfolded protein response . Blood . 2006; March 21, (Epub ahead of print)
  22. Skokowa J , Cario G , Bucan V , Dan L , Wang Z , Scherr M , et al.   LEF-1 transcription factor regulates proliferation and differentiation of myeloid progenitors in healthy individuals and in patients with severe congenital neutropenia (CN) . Blood . 2005;106:390a; (abstr)
  23. Bernard T , Gale R , Evans J , Linch DC . Mutations of the granulocyte-colony stimulating factor receptor in patients with severe congenital neutropenia are not required for transformation to acute myeloid leukaemia and may be a bystander phenomenon . Br J Haematol . 1998;101:141–149
  24. Cassinat B , Bellanné-Chantelot C , Notz-Carrère A , Menot ML , Vaury C , Micheau M , et al.  Screening for G-CSF receptor mutations in patients with secondary myeloid or lymphoid transformation of severe congenital neutropenia. A report from the French Neutropenia Register . Leukemia . 2004;18:1553–1555
  25. Dong F , Russel KB , Tidow N , Freedman M , Fasth A , Neijens HJ , et al.  Mutations in the gene for the granulocyte-colony stimulating factor receptor in patients with acute myeloid leukemia preceded by severe congenital neutropenia . N Engl J Med . 1995;333:487–493
  26. Germeshausen M , Schulze H , Kratz C , Wilkens L , Repp R , Shannon K , et al.  An acquired G-CSF receptor mutation results in increased proliferation of CMML cells from a patient with severe congenital neutropenia . Leukemia . 2005;19:611–617
  27. Papadaki HA , Kosteas T , Gemetzi C , Damianaki A , Anagnou NP , Eliopoulos GD . Acute myeloid/NK precursor cell leukemia with trisomy 4 and a novel point mutation in the extracellular domain of the G-CSF receptor in a patient with chronic idiopathic neutropenia . Ann Hematol . 2004;83:345–348
  28. Tidow N , Pilz C , Teichmann B , Muller-Brechlin A , Germeshausen M , Kasper B , et al.  Clinical relevance of point mutations in the cytoplasmatic domain of the granulocyte-colony stimulating factor gene in patients with severe congenital neutropenia . Blood . 1997;88:2369–2375
  29. Tschan CA , Pilz C , Zeidler C , Welte K , Germeshausen M . Time course of increasing numbers of mutations in the granulocyte colony-stimulating factor receptor gene in a patient with congenital neutropenia who developed leukemia . Blood . 2001;97:1882–1884
  30. Jeha S , Chan KW , Aprikyan AG , Hoots WK , Culbert S , Zietz H , et al.  Spontaneous remission of granulocyte colony-stimulating factor–associated leukemia in a child with severe congenital neutropenia . Blood . 2000;96:3647–3649
  31. Bux J , Behrens G , Jaeger G , Welte K . Diagnosis and clinical course of autoimmune neutropenia in infancy (Analysis of 240 cases) . Blood . 1998;91:181–186
  32. Dale D , Bonilla M , Davis M , Nakanishi AM , Hammond WP , Kurtzberg J , 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
  33. Welte K, Zeidler C, Reiter A, Muller W, Odenwald E, Souza L, 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
  34. Zeidler C , Vogel R , Wyres M , et al.   Beneficial effects of stem cell factor (SCF) in children with severe congenital neutropenias refractory to G-CSF . Blood . 1998;92:380a; (abstr)
  35. Gilman P , Jackson D , Guild H . Congenital agranulocytosis (Prolonged survival and terminal acute leukemia) . Blood . 1971;36:576–585
  36. Rosen R , Kang S . Congenital agranulocytosis terminating in acute myelomonocytic leukemia . J Pediatr . 1979;94:406–408
  37. 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; February 23, (Epub ahead of print)
  38. Yakisan E , Schirg E , Zeidler C , Bischop NJ , Reiter A , et al.  High incidence of significant bone loss in patients with severe congenital neutropenia (Kostmann’s syndrome) . J Pediatr . 1997;131:592–597

PII: S0037-1963(06)00078-3

doi: 10.1053/j.seminhematol.2006.04.004

Seminars in Hematology
Volume 43, Issue 3 , Pages 189-195 , July 2006