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* There is no established system for the [[classification]] of cyclic neutropenia. | * There is no established system for the [[classification]] of cyclic neutropenia. | ||
==Pathophysiology== | ==Pathophysiology== | ||
* Cyclic neutropenia is caused by | * Normal neutrophilic counts is typically between 1500 to 8500 cells/μl after the age of one year.<ref name="ManroeWeinberg1979">{{cite journal|last1=Manroe|first1=Barbara L.|last2=Weinberg|first2=Arthur G.|last3=Rosenfeld|first3=Charles R.|last4=Browne|first4=Richard|title=The neonatal blood count in health and disease.I. Reference values for neutrophilic cells|journal=The Journal of Pediatrics|volume=95|issue=1|year=1979|pages=89–98|issn=00223476|doi=10.1016/S0022-3476(79)80096-7}}</ref> | ||
* Cyclic neutropenia is caused by heterozygous mutation in the ELA2 (ELANE) gene.<ref name="DaleBolyard2002">{{cite journal|last1=Dale|first1=David C.|last2=Bolyard|first2=Audrey Anna|last3=Aprikyan|first3=Andrew|title=Cyclic neutropenia|journal=Seminars in Hematology|volume=39|issue=2|year=2002|pages=89–94|issn=00371963|doi=10.1053/shem.2002.31917}}</ref><ref name="HorwitzCorey2013">{{cite journal|last1=Horwitz|first1=Marshall S.|last2=Corey|first2=Seth J.|last3=Grimes|first3=H. Leighton|last4=Tidwell|first4=Timothy|title=ELANE Mutations in Cyclic and Severe Congenital Neutropenia|journal=Hematology/Oncology Clinics of North America|volume=27|issue=1|year=2013|pages=19–41|issn=08898588|doi=10.1016/j.hoc.2012.10.004}}</ref> | |||
* The disease occurs in autosomal dominant mode of inheritance. | * The disease occurs in autosomal dominant mode of inheritance. | ||
* The culprit gene is responsible for encoding the neutrophil granule serine protease, neutrophil elastase. | |||
* Mutation results in abnormal gene product that damages cells while they mature, leading to te failure of cell production. | |||
* Theoretically, this [[disorder]] can be cured by bone marrow transplantation. This demonstrates its pathogenesis as the stem cell abnormality.<ref name="pmid7036779">{{cite journal |vauthors=Lange RD, Jones JB |title=Cyclic neutropenia. Review of clinical manifestations and management |journal=Am J Pediatr Hematol Oncol |volume=3 |issue=4 |pages=363–7 |date=1981 |pmid=7036779 |doi= |url=}}</ref> | * Theoretically, this [[disorder]] can be cured by bone marrow transplantation. This demonstrates its pathogenesis as the stem cell abnormality.<ref name="pmid7036779">{{cite journal |vauthors=Lange RD, Jones JB |title=Cyclic neutropenia. Review of clinical manifestations and management |journal=Am J Pediatr Hematol Oncol |volume=3 |issue=4 |pages=363–7 |date=1981 |pmid=7036779 |doi= |url=}}</ref> | ||
* This stem cell abnormality leads to the myelocyte maturation arrest during neutropenia episodes. | * This stem cell abnormality leads to the myelocyte maturation arrest during neutropenia episodes. | ||
==Causes== | ==Causes== | ||
* Cyclic neutropenia is caused by | * Cyclic neutropenia is caused by heterozygous mutation in the ELA2 (ELANE) gene.<ref name="HorwitzCorey2013">{{cite journal|last1=Horwitz|first1=Marshall S.|last2=Corey|first2=Seth J.|last3=Grimes|first3=H. Leighton|last4=Tidwell|first4=Timothy|title=ELANE Mutations in Cyclic and Severe Congenital Neutropenia|journal=Hematology/Oncology Clinics of North America|volume=27|issue=1|year=2013|pages=19–41|issn=08898588|doi=10.1016/j.hoc.2012.10.004}}</ref> | ||
==Differentiating Cyclic neutropenia from Other Diseases== | ==Differentiating Cyclic neutropenia from Other Diseases== | ||
* Cyclic neutropenia should be differentiated from other disorders manifesting with recurrent [[fever]], [[aphthous stomatitis]], and [[pharyngitis]]. These include [[PFAPA syndrome]], monogenic [[autoinflammatory disorders]] such as [[FMF]], [[CAPS]], and [[TRAPS]], as well as primary immunodeficincies.<ref name="AliSartori-Valinotti2016">{{cite journal|last1=Ali|first1=Nora S.|last2=Sartori-Valinotti|first2=Julio C.|last3=Bruce|first3=Alison J.|title=Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome|journal=Clinics in Dermatology|volume=34|issue=4|year=2016|pages=482–486|issn=0738081X|doi=10.1016/j.clindermatol.2016.02.021}}</ref> | * Cyclic neutropenia should be differentiated from other disorders manifesting with recurrent [[fever]], [[aphthous stomatitis]], and [[pharyngitis]]. These include [[PFAPA syndrome]], monogenic [[autoinflammatory disorders]] such as [[FMF]], [[CAPS]], and [[TRAPS]], as well as primary immunodeficincies.<ref name="AliSartori-Valinotti2016">{{cite journal|last1=Ali|first1=Nora S.|last2=Sartori-Valinotti|first2=Julio C.|last3=Bruce|first3=Alison J.|title=Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome|journal=Clinics in Dermatology|volume=34|issue=4|year=2016|pages=482–486|issn=0738081X|doi=10.1016/j.clindermatol.2016.02.021}}</ref> | ||
* Shwachman-Diamond syndrome may also present with [[neutropenia]]. However, its [[diagnosis]] requires some [[dysmorphic]] features which are not present in patients with cyclic neutropenia.<ref name="pmid10393609">{{cite journal |vauthors=Ginzberg H, Shin J, Ellis L, Morrison J, Ip W, Dror Y, Freedman M, Heitlinger LA, Belt MA, Corey M, Rommens JM, Durie PR |title=Shwachman syndrome: phenotypic manifestations of sibling sets and isolated cases in a large patient cohort are similar |journal=J. Pediatr. |volume=135 |issue=1 |pages=81–8 |date=July 1999 |pmid=10393609 |doi=10.1016/s0022-3476(99)70332-x |url=}}</ref> | * Shwachman-Diamond syndrome may also present with [[neutropenia]]. However, its [[diagnosis]] requires some [[dysmorphic]] features which are not present in patients with cyclic neutropenia.<ref name="pmid10393609">{{cite journal |vauthors=Ginzberg H, Shin J, Ellis L, Morrison J, Ip W, Dror Y, Freedman M, Heitlinger LA, Belt MA, Corey M, Rommens JM, Durie PR |title=Shwachman syndrome: phenotypic manifestations of sibling sets and isolated cases in a large patient cohort are similar |journal=J. Pediatr. |volume=135 |issue=1 |pages=81–8 |date=July 1999 |pmid=10393609 |doi=10.1016/s0022-3476(99)70332-x |url=}}</ref> | ||
* For more information on cyclic neutropenia [[differential diagnosis]] please [[Neutropenia differential diagnosis|click here]]. | * For more information on cyclic neutropenia [[differential diagnosis]] please [[Neutropenia differential diagnosis|click here]]. | ||
==Epidemiology and Demographics== | ==Epidemiology and Demographics== | ||
* The incidence of cyclic neutropenia is 0.010-0.02 per 100,000 individuals worldwide.<ref name="pmid14962902">{{cite journal |vauthors=Bellanné-Chantelot C, Clauin S, Leblanc T, Cassinat B, Rodrigues-Lima F, Beaufils S, Vaury C, Barkaoui M, Fenneteau O, Maier-Redelsperger M, Chomienne C, Donadieu J |title=Mutations in the ELA2 gene correlate with more severe expression of neutropenia: a study of 81 patients from the French Neutropenia Register |journal=Blood |volume=103 |issue=11 |pages=4119–25 |date=June 2004 |pmid=14962902 |doi=10.1182/blood-2003-10-3518 |url=}}</ref> | * The incidence of cyclic neutropenia is 0.010-0.02 per 100,000 individuals worldwide.<ref name="pmid14962902">{{cite journal |vauthors=Bellanné-Chantelot C, Clauin S, Leblanc T, Cassinat B, Rodrigues-Lima F, Beaufils S, Vaury C, Barkaoui M, Fenneteau O, Maier-Redelsperger M, Chomienne C, Donadieu J |title=Mutations in the ELA2 gene correlate with more severe expression of neutropenia: a study of 81 patients from the French Neutropenia Register |journal=Blood |volume=103 |issue=11 |pages=4119–25 |date=June 2004 |pmid=14962902 |doi=10.1182/blood-2003-10-3518 |url=}}</ref> | ||
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* Disease manifests in early years of life with episodes of [[fever]] occurring every 21 days (range from 14 to 35 days).<ref name="pmid11957190">{{cite journal |vauthors=Dale DC, Bolyard AA, Aprikyan A |title=Cyclic neutropenia |journal=Semin. Hematol. |volume=39 |issue=2 |pages=89–94 |date=April 2002 |pmid=11957190 |doi= |url=}}</ref> | * Disease manifests in early years of life with episodes of [[fever]] occurring every 21 days (range from 14 to 35 days).<ref name="pmid11957190">{{cite journal |vauthors=Dale DC, Bolyard AA, Aprikyan A |title=Cyclic neutropenia |journal=Semin. Hematol. |volume=39 |issue=2 |pages=89–94 |date=April 2002 |pmid=11957190 |doi= |url=}}</ref> | ||
* The hallmark of this [[disorder]] is the predictability of the fever episodes. | * The hallmark of this [[disorder]] is the predictability of the fever episodes. | ||
* Patients may | * Patients may be asymptomatic or develop life-threatening infections depending on the severity of neutropenia. | ||
* During episodes, [[patients]] are neutropenic and it increases their risk for [[dental]] and [[gingival]] [[complications]].<ref name="PalmerStephens1996">{{cite journal|last1=Palmer|first1=Susan E.|last2=Stephens|first2=Karen|last3=Dale|first3=David C.|title=Genetics, phenotype, and natural history of autosomal dominant cyclic hematopoiesis|journal=American Journal of Medical Genetics|volume=66|issue=4|year=1996|pages=413–422|issn=01487299|doi=10.1002/(SICI)1096-8628(19961230)66:4<413::AID-AJMG5>3.0.CO;2-L}}</ref> | * During episodes, [[patients]] are neutropenic and it increases their risk for [[dental]] and [[gingival]] [[complications]].<ref name="PalmerStephens1996">{{cite journal|last1=Palmer|first1=Susan E.|last2=Stephens|first2=Karen|last3=Dale|first3=David C.|title=Genetics, phenotype, and natural history of autosomal dominant cyclic hematopoiesis|journal=American Journal of Medical Genetics|volume=66|issue=4|year=1996|pages=413–422|issn=01487299|doi=10.1002/(SICI)1096-8628(19961230)66:4<413::AID-AJMG5>3.0.CO;2-L}}</ref> | ||
* Although [[patients]] with cyclic neutropenia are not as immunodeficient as the post-chemotherapy [[patients]], they still should not be assumed normal. | * Although [[patients]] with cyclic neutropenia are not as immunodeficient as the post-chemotherapy [[patients]], they still should not be assumed normal. | ||
* Serious [[complications]] of this disorder include [[pneumonia]], [[mastoiditis]], and [[bacterial]] [[cutaneous]] and [[subcutaneous infections]].<ref name="GlavanRoganović2015">{{cite journal|last1=Glavan|first1=Nedeljka|last2=Roganović|first2=Jelena|last3=Glavan-Gacanin|first3=Lana|last4=Jonjic|first4=Nives|title=Appendectomy in a child with cyclic neutropenia in profound neutropenic episode|journal=Therapeutics and Clinical Risk Management|year=2015|pages=1217|issn=1178-203X|doi=10.2147/TCRM.S89488}}</ref> | * Serious [[complications]] of this disorder include [[pneumonia]], [[mastoiditis]], and [[bacterial]] [[cutaneous]] and [[subcutaneous infections]].<ref name="GlavanRoganović2015">{{cite journal|last1=Glavan|first1=Nedeljka|last2=Roganović|first2=Jelena|last3=Glavan-Gacanin|first3=Lana|last4=Jonjic|first4=Nives|title=Appendectomy in a child with cyclic neutropenia in profound neutropenic episode|journal=Therapeutics and Clinical Risk Management|year=2015|pages=1217|issn=1178-203X|doi=10.2147/TCRM.S89488}}</ref> | ||
* Death induced by [[infections]] are a possible [[complication]] of this [[disorder]]. | * Death induced by [[infections]] are a possible [[complication]] of this [[disorder]] and has been reported in 10% of the [[patients]].<ref name="DaleCottle2003">{{cite journal|last1=Dale|first1=David C.|last2=Cottle|first2=Tammy E.|last3=Fier|first3=Carol J.|last4=Bolyard|first4=Audrey Anna|last5=Bonilla|first5=Mary Ann|last6=Boxer|first6=Laurence A.|last7=Cham|first7=Bonnie|last8=Freedman|first8=Melvin H.|last9=Kannourakis|first9=George|last10=Kinsey|first10=Sally E.|last11=Davis|first11=Robert|last12=Scarlata|first12=Debra|last13=Schwinzer|first13=Beate|last14=Zeidler|first14=Cornelia|last15=Welte|first15=Karl|title=Severe chronic neutropenia: Treatment and follow-up of patients in the Severe Chronic Neutropenia International Registry|journal=American Journal of Hematology|volume=72|issue=2|year=2003|pages=82–93|issn=0361-8609|doi=10.1002/ajh.10255}}</ref> | ||
==Diagnosis== | ==Diagnosis== | ||
===Diagnostic Criteria=== | ===Diagnostic Criteria=== | ||
| Line 43: | Line 44: | ||
===Physical Examination=== | ===Physical Examination=== | ||
* [[Physical examination]] of [[patients]] with cyclic neutropenia include:<ref name="pmid8989458">{{cite journal |vauthors=Palmer SE, Stephens K, Dale DC |title=Genetics, phenotype, and natural history of autosomal dominant cyclic hematopoiesis |journal=Am. J. Med. Genet. |volume=66 |issue=4 |pages=413–22 |date=December 1996 |pmid=8989458 |doi=10.1002/(SICI)1096-8628(19961230)66:4<413::AID-AJMG5>3.0.CO;2-L |url=}}</ref> | * [[Physical examination]] of [[patients]] with cyclic neutropenia include:<ref name="pmid8989458">{{cite journal |vauthors=Palmer SE, Stephens K, Dale DC |title=Genetics, phenotype, and natural history of autosomal dominant cyclic hematopoiesis |journal=Am. J. Med. Genet. |volume=66 |issue=4 |pages=413–22 |date=December 1996 |pmid=8989458 |doi=10.1002/(SICI)1096-8628(19961230)66:4<413::AID-AJMG5>3.0.CO;2-L |url=}}</ref> | ||
** Fever | ** [[Fever]] | ||
** Pharyngitis | ** [[Pharyngitis]] | ||
** Gingival inflammation and edema | ** [[Gingival]] [[inflammation]] and [[edema]] | ||
===Laboratory Findings=== | ===Laboratory Findings=== | ||
* Laboratory findings associated with the [[diagnosis]] of cyclic neutropenia include: | * Laboratory findings associated with the [[diagnosis]] of cyclic neutropenia include:<ref name="GlavanRoganović2015">{{cite journal|last1=Glavan|first1=Nedeljka|last2=Roganović|first2=Jelena|last3=Glavan-Gacanin|first3=Lana|last4=Jonjic|first4=Nives|title=Appendectomy in a child with cyclic neutropenia in profound neutropenic episode|journal=Therapeutics and Clinical Risk Management|year=2015|pages=1217|issn=1178-203X|doi=10.2147/TCRM.S89488}}</ref> | ||
** Low absolute neutrophilic count | ** Low absolute neutrophilic count | ||
** Neutropenia may be mild or severe with a nadir of 100/μL for 3–6 days in each cycle. However, th duration of neutropenia varies between the [[patients]]. | |||
===Electrocardiogram=== | ===Electrocardiogram=== | ||
* There are no [[ECG]] findings associated with cyclic neutropenia. | * There are no [[ECG]] findings associated with cyclic neutropenia. | ||
Revision as of 16:12, 25 September 2019
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sahar Memar Montazerin, M.D.[2]
Synonyms and keywords: Cyclic hematopoiesis
Overview
Cyclic neutropenia is a condition in which the neutrophil count periodically and regularly rises and falls. It is rarely observed in humans, but has been observed in the Grey Collie dog.
Historical Perspective
- Cyclic neutropenia first described in the year 1910 in an infant with recurrent fever.[1]
Classification
- There is no established system for the classification of cyclic neutropenia.
Pathophysiology
- Normal neutrophilic counts is typically between 1500 to 8500 cells/μl after the age of one year.[2]
- Cyclic neutropenia is caused by heterozygous mutation in the ELA2 (ELANE) gene.[1][3]
- The disease occurs in autosomal dominant mode of inheritance.
- The culprit gene is responsible for encoding the neutrophil granule serine protease, neutrophil elastase.
- Mutation results in abnormal gene product that damages cells while they mature, leading to te failure of cell production.
- Theoretically, this disorder can be cured by bone marrow transplantation. This demonstrates its pathogenesis as the stem cell abnormality.[4]
- This stem cell abnormality leads to the myelocyte maturation arrest during neutropenia episodes.
Causes
- Cyclic neutropenia is caused by heterozygous mutation in the ELA2 (ELANE) gene.[3]
Differentiating Cyclic neutropenia from Other Diseases
- Cyclic neutropenia should be differentiated from other disorders manifesting with recurrent fever, aphthous stomatitis, and pharyngitis. These include PFAPA syndrome, monogenic autoinflammatory disorders such as FMF, CAPS, and TRAPS, as well as primary immunodeficincies.[5]
- Shwachman-Diamond syndrome may also present with neutropenia. However, its diagnosis requires some dysmorphic features which are not present in patients with cyclic neutropenia.[6]
- For more information on cyclic neutropenia differential diagnosis please click here.
Epidemiology and Demographics
- The incidence of cyclic neutropenia is 0.010-0.02 per 100,000 individuals worldwide.[7]
- There is no racial predilection to cyclic neutropenia.
- Cyclic neutropenia affects men and women equally.
Risk Factors
- There are no established risk factors for cyclic neutropenia.
Screening
- There is insufficient evidence to recommend routine screening for cyclic neutropenia.
Natural History, Complications, and Prognosis
- Disease manifests in early years of life with episodes of fever occurring every 21 days (range from 14 to 35 days).[8]
- The hallmark of this disorder is the predictability of the fever episodes.
- Patients may be asymptomatic or develop life-threatening infections depending on the severity of neutropenia.
- During episodes, patients are neutropenic and it increases their risk for dental and gingival complications.[9]
- Although patients with cyclic neutropenia are not as immunodeficient as the post-chemotherapy patients, they still should not be assumed normal.
- Serious complications of this disorder include pneumonia, mastoiditis, and bacterial cutaneous and subcutaneous infections.[10]
- Death induced by infections are a possible complication of this disorder and has been reported in 10% of the patients.[11]
Diagnosis
Diagnostic Criteria
History and Symptoms
- Symptoms of cyclic neutropenia include fever, malaise, oral ulcers, gingival inflammation, edema, and sore throat.[12][4]
Physical Examination
- Physical examination of patients with cyclic neutropenia include:[12]
Laboratory Findings
- Laboratory findings associated with the diagnosis of cyclic neutropenia include:[10]
- Low absolute neutrophilic count
- Neutropenia may be mild or severe with a nadir of 100/μL for 3–6 days in each cycle. However, th duration of neutropenia varies between the patients.
Electrocardiogram
- There are no ECG findings associated with cyclic neutropenia.
X-ray
- There are no x-ray findings associated with cyclic neutropenia.
Echocardiography or Ultrasound
- There are no echocardiography/ultrasound findings associated with cyclic neutropenia.
CT Scan
- There are no CT scan findings associated with cyclic neutropenia.
MRI
- There are no MRI findings associated with cyclic neutropenia.
Other Imaging Findings
- There are no other imaging findings associated with cyclic neutropenia.
Other Diagnostic Studies
- There are no other diagnostic studies associated with cyclic neutropenia.
Treatment
Medical Therapy
- The mainstay of treatment for cyclic neutropenia is medical therapy.[13][14]
- Granulocyte colony-stimulating factor (G-CSF) may be used to treat cyclic neutropenia.
Surgery
- Surgical intervention is not recommended for the management of cyclic neutropenia.
Primary Prevention
- There are no established measures for the primary prevention of cyclic neutropenia.
Secondary Prevention
- There are no established measures for the secondary prevention of cyclic neutropenia.
References
- ↑ 1.0 1.1 Dale, David C.; Bolyard, Audrey Anna; Aprikyan, Andrew (2002). "Cyclic neutropenia". Seminars in Hematology. 39 (2): 89–94. doi:10.1053/shem.2002.31917. ISSN 0037-1963.
- ↑ Manroe, Barbara L.; Weinberg, Arthur G.; Rosenfeld, Charles R.; Browne, Richard (1979). "The neonatal blood count in health and disease.I. Reference values for neutrophilic cells". The Journal of Pediatrics. 95 (1): 89–98. doi:10.1016/S0022-3476(79)80096-7. ISSN 0022-3476.
- ↑ 3.0 3.1 Horwitz, Marshall S.; Corey, Seth J.; Grimes, H. Leighton; Tidwell, Timothy (2013). "ELANE Mutations in Cyclic and Severe Congenital Neutropenia". Hematology/Oncology Clinics of North America. 27 (1): 19–41. doi:10.1016/j.hoc.2012.10.004. ISSN 0889-8588.
- ↑ 4.0 4.1 Lange RD, Jones JB (1981). "Cyclic neutropenia. Review of clinical manifestations and management". Am J Pediatr Hematol Oncol. 3 (4): 363–7. PMID 7036779.
- ↑ Ali, Nora S.; Sartori-Valinotti, Julio C.; Bruce, Alison J. (2016). "Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome". Clinics in Dermatology. 34 (4): 482–486. doi:10.1016/j.clindermatol.2016.02.021. ISSN 0738-081X.
- ↑ Ginzberg H, Shin J, Ellis L, Morrison J, Ip W, Dror Y, Freedman M, Heitlinger LA, Belt MA, Corey M, Rommens JM, Durie PR (July 1999). "Shwachman syndrome: phenotypic manifestations of sibling sets and isolated cases in a large patient cohort are similar". J. Pediatr. 135 (1): 81–8. doi:10.1016/s0022-3476(99)70332-x. PMID 10393609.
- ↑ Bellanné-Chantelot C, Clauin S, Leblanc T, Cassinat B, Rodrigues-Lima F, Beaufils S, Vaury C, Barkaoui M, Fenneteau O, Maier-Redelsperger M, Chomienne C, Donadieu J (June 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 (11): 4119–25. doi:10.1182/blood-2003-10-3518. PMID 14962902.
- ↑ Dale DC, Bolyard AA, Aprikyan A (April 2002). "Cyclic neutropenia". Semin. Hematol. 39 (2): 89–94. PMID 11957190.
- ↑ Palmer, Susan E.; Stephens, Karen; Dale, David C. (1996). "Genetics, phenotype, and natural history of autosomal dominant cyclic hematopoiesis". American Journal of Medical Genetics. 66 (4): 413–422. doi:10.1002/(SICI)1096-8628(19961230)66:4<413::AID-AJMG5>3.0.CO;2-L. ISSN 0148-7299.
- ↑ 10.0 10.1 Glavan, Nedeljka; Roganović, Jelena; Glavan-Gacanin, Lana; Jonjic, Nives (2015). "Appendectomy in a child with cyclic neutropenia in profound neutropenic episode". Therapeutics and Clinical Risk Management: 1217. doi:10.2147/TCRM.S89488. ISSN 1178-203X.
- ↑ Dale, David C.; Cottle, Tammy E.; Fier, Carol J.; Bolyard, Audrey Anna; Bonilla, Mary Ann; Boxer, Laurence A.; Cham, Bonnie; Freedman, Melvin H.; Kannourakis, George; Kinsey, Sally E.; Davis, Robert; Scarlata, Debra; Schwinzer, Beate; Zeidler, Cornelia; Welte, Karl (2003). "Severe chronic neutropenia: Treatment and follow-up of patients in the Severe Chronic Neutropenia International Registry". American Journal of Hematology. 72 (2): 82–93. doi:10.1002/ajh.10255. ISSN 0361-8609.
- ↑ 12.0 12.1 Palmer SE, Stephens K, Dale DC (December 1996). "Genetics, phenotype, and natural history of autosomal dominant cyclic hematopoiesis". Am. J. Med. Genet. 66 (4): 413–22. doi:10.1002/(SICI)1096-8628(19961230)66:4<413::AID-AJMG5>3.0.CO;2-L. PMID 8989458.
- ↑ Hammond WP, Price TH, Souza LM, Dale DC (May 1989). "Treatment of cyclic neutropenia with granulocyte colony-stimulating factor". N. Engl. J. Med. 320 (20): 1306–11. doi:10.1056/NEJM198905183202003. PMID 2469956.
- ↑ Bonilla MA, Dale D, Zeidler C, Last L, Reiter A, Ruggeiro M, Davis M, Koci B, Hammond W, Gillio A (December 1994). "Long-term safety of treatment with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) in patients with severe congenital neutropenias". Br. J. Haematol. 88 (4): 723–30. doi:10.1111/j.1365-2141.1994.tb05110.x. PMID 7529539.