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Cyclic neutropenia

INTRODUCTION

This topic review discusses cyclic neutropenia (also called cyclic hematopoiesis), which, in contrast to other rare congenital neutropenias, tends to be mild and benign, but can occasionally be severe.

Other causes of neutropenia are discussed separately. (See "Overview of neutropenia in children and adolescents" and "Congenital neutropenia" and "Approach to the adult with unexplained neutropenia".)

DISEASE OVERVIEW

Cyclic neutropenia is a rare, autosomal dominantly inherited disorder with variable expression and an estimated incidence of one to two per million [1,2]. It is characterized by neutropenia that recurs every 14 to 35 days, although over 90 percent of patients exhibit a cycle period of 21 days [3]. While the disease tends to be benign, several affected patients have died of infection [4]. Most of the patients present in the first year of life.

There is an acquired adult onset form of cyclic neutropenia; however, it is autoimmune rather than genetic in nature and has been found in association with T cell large granular lymphocyte leukemia. (See "Clinical manifestations, pathologic features, and diagnosis of T cell large granular lymphocyte leukemia", section on 'Clinical features'.)

PATHOGENESIS

Cyclic neutropenia can be cured by hematopoietic cell transplantation in an animal model [4] and has been transferred from an affected human donor to a recipient following hematopoietic cell transplantation [5], demonstrating that this disorder is an intrinsic disorder of bone marrow stem cells.

        

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Literature review current through: Oct 2014. | This topic last updated: Mar 4, 2014.
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References
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  1. Bellanné-Chantelot C, Clauin S, Leblanc T, et al. Mutations in the ELA2 gene correlate with more severe expression of neutropenia: a study of 81 patients from the French Neutropenia Register. Blood 2004; 103:4119.
  2. Dale DC. ELANE-related neutropenia. In: GeneReviews, Pagon RA, Dolan CR, Stephens K (Eds), University of Washington, Seattle 2009.
  3. Dale DC, Bolyard AA, Aprikyan A. Cyclic neutropenia. Semin Hematol 2002; 39:89.
  4. Lange RD, Jones JB. Cyclic neutropenia. Review of clinical manifestations and management. Am J Pediatr Hematol Oncol 1981; 3:363.
  5. Krance RA, Spruce WE, Forman SJ, et al. Human cyclic neutropenia transferred by allogeneic bone marrow grafting. Blood 1982; 60:1263.
  6. Leale M. Recurrent furunculosis in an infant showing unusual blood picture. JAMA 1910; 54:1854.
  7. Rutledge B, Hansen-Pruss O, Thayer W. Recurrent agranulocytosis. Bull Johns Hopkins Hosp 1930; 46:369.
  8. Aprikyan AA, Liles WC, Rodger E, et al. Impaired survival of bone marrow hematopoietic progenitor cells in cyclic neutropenia. Blood 2001; 97:147.
  9. Haurie C, Dale DC, Mackey MC. Cyclical neutropenia and other periodic hematological disorders: a review of mechanisms and mathematical models. Blood 1998; 92:2629.
  10. Aprikyan AA, Dale DC. Mutations in the neutrophil elastase gene in cyclic and congenital neutropenia. Curr Opin Immunol 2001; 13:535.
  11. Horwitz M, Benson KF, Duan Z, et al. Role of neutrophil elastase in bone marrow failure syndromes: molecular genetic revival of the chalone hypothesis. Curr Opin Hematol 2003; 10:49.
  12. Dale DC, Person RE, Bolyard AA, et al. Mutations in the gene encoding neutrophil elastase in congenital and cyclic neutropenia. Blood 2000; 96:2317.
  13. Horwitz M, Benson KF, Person RE, et al. Mutations in ELA2, encoding neutrophil elastase, define a 21-day biological clock in cyclic haematopoiesis. Nat Genet 1999; 23:433.
  14. Rosenberg PS, Alter BP, Bolyard AA, et al. The incidence of leukemia and mortality from sepsis in patients with severe congenital neutropenia receiving long-term G-CSF therapy. Blood 2006; 107:4628.
  15. Armistead PM, Wieder E, Akande O, et al. Cyclic neutropenia associated with T cell immunity to granulocyte proteases and a double de novo mutation in GFI1, a transcriptional regulator of ELANE. Br J Haematol 2010; 150:716.
  16. Palmer SE, Stephens K, Dale DC. Genetics, phenotype, and natural history of autosomal dominant cyclic hematopoiesis. Am J Med Genet 1996; 66:413.
  17. Sievers EL, Dale DC. Non-malignant neutropenia. Blood Rev 1996; 10:95.
  18. Bar-Joseph G, Halberthal M, Sweed Y, et al. Clostridium septicum infection in children with cyclic neutropenia. J Pediatr 1997; 131:317.
  19. Marshall GS, Edwards KM, Butler J, Lawton AR. Syndrome of periodic fever, pharyngitis, and aphthous stomatitis. J Pediatr 1987; 110:43.
  20. Horwitz MS, Duan Z, Korkmaz B, et al. Neutrophil elastase in cyclic and severe congenital neutropenia. Blood 2007; 109:1817.
  21. Welte K, Boxer LA. Severe chronic neutropenia: pathophysiology and therapy. Semin Hematol 1997; 34:267.
  22. Hammond WP 4th, Price TH, Souza LM, Dale DC. Treatment of cyclic neutropenia with granulocyte colony-stimulating factor. N Engl J Med 1989; 320:1306.
  23. Matarasso S, Daniele V, Iorio Siciliano V, et al. The effect of recombinant granulocyte colony-stimulating factor on oral and periodontal manifestations in a patient with cyclic neutropenia: a case report. Int J Dent 2009; 2009:654239.
  24. Bonilla MA, Dale D, Zeidler C, 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 Haematol 1994; 88:723.
  25. Heussner P, Haase D, Kanz L, et al. G-CSF in the long-term treatment of cyclic neutropenia and chronic idiopathic neutropenia in adult patients. Int J Hematol 1995; 62:225.
  26. Dale DC, Bolyard AA, Hammond WP. Cyclic neutropenia: natural history and effects of long-term treatment with recombinant human granulocyte colony-stimulating factor. Cancer Invest 1993; 11:219.
  27. 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.
  28. Jayabose S, Tugal O, Sandoval C, Li K. Recombinant human granulocyte colony stimulating factor in cyclic neutropenia: use of a new 3-day-a-week regimen. Am J Pediatr Hematol Oncol 1994; 16:338.
  29. Dale DC, Welte K. Cyclic and chronic neutropenia. Cancer Treat Res 2011; 157:97.