Chronic neutrophilic leukemia: Difference between revisions

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==[[Chronic neutrophilic leukemia screening|Screening]]==
==[[Chronic neutrophilic leukemia screening|Screening]]==


==Natural History, Complications, and Prognosis==
==[[Chronic neutrophilic leukemia natural history, complications and prognosis|Natural History, Complications and Prognosis]]==
Progression to acute myeloid leukemia may seen in 10-21.2% of patients with CNL.<ref name="Elliott2006">{{cite journal|last1=Elliott|first1=Michelle A.|title=Chronic neutrophilic leukemia and chronic myelomonocytic leukemia: WHO defined|journal=Best Practice & Research Clinical Haematology|volume=19|issue=3|year=2006|pages=571–593|issn=15216926|doi=10.1016/j.beha.2005.07.012}}</ref><ref name="Reilly2002">{{cite journal|last1=Reilly|first1=John T.|title=CHRONIC NEUTROPHILIC LEUKAEMIA: A DISTINCT CLINICAL ENTITY?|journal=British Journal of Haematology|volume=116|issue=1|year=2002|pages=10–18|issn=0007-1048|doi=10.1046/j.1365-2141.2002.03234.x}}</ref>
 
Prognosis is generally poor, and the 5-year survival rate of patients with CNL is approximately 28%.<ref name="Reilly2002">{{cite journal|last1=Reilly|first1=John T.|title=CHRONIC NEUTROPHILIC LEUKAEMIA: A DISTINCT CLINICAL ENTITY?|journal=British Journal of Haematology|volume=116|issue=1|year=2002|pages=10–18|issn=0007-1048|doi=10.1046/j.1365-2141.2002.03234.x}}</ref><ref>{{Cite journal
| author = [[J. Bohm]] & [[H. E. Schaefer]]
| title = Chronic neutrophilic leukaemia: 14 new cases of an uncommon myeloproliferative disease
| journal = [[Journal of clinical pathology]]
| volume = 55
| issue = 11
| pages = 862–864
| year = 2002
| month = November
| pmid = 12401827
}}</ref>
 
The factors that can predict poor outcomes are:<ref name="DaoTyner2017">{{cite journal|last1=Dao|first1=Kim-Hien T.|last2=Tyner|first2=Jeffrey W.|last3=Gotlib|first3=Jason|title=Recent Progress in Chronic Neutrophilic Leukemia and Atypical Chronic Myeloid Leukemia|journal=Current Hematologic Malignancy Reports|volume=12|issue=5|year=2017|pages=432–441|issn=1558-8211|doi=10.1007/s11899-017-0413-y}}</ref><ref name="ElliottPardanani2015">{{cite journal|last1=Elliott|first1=Michelle A.|last2=Pardanani|first2=Animesh|last3=Hanson|first3=Curtis A.|last4=Lasho|first4=Terra L.|last5=Finke|first5=Christy M.|last6=Belachew|first6=Alem A.|last7=Tefferi|first7=Ayalew|title=ASXL1mutations are frequent and prognostically detrimental inCSF3R-mutated chronic neutrophilic leukemia|journal=American Journal of Hematology|volume=90|issue=7|year=2015|pages=653–656|issn=03618609|doi=10.1002/ajh.24031}}</ref><ref>{{Cite journal
| author = [[Massimo Breccia]], [[Francesca Biondo]], [[Roberto Latagliata]], [[Ida Carmosino]], [[Franco Mandelli]] & [[Giuliana Alimena]]
| title = Identification of risk factors in atypical chronic myeloid leukemia
| journal = [[Haematologica]]
| volume = 91
| issue = 11
| pages = 1566–1568
| year = 2006
| month = November
| pmid = 17043019
}}</ref>
* white blood cell count>50,000 cells per microliter
* ASXL1 mutation
* Thrombocytopenia
* Advanced age
* Dependency to transfusion
* Peripheral blasts ≥ 1%
* Marrow blasts ≥ 10% 
* Splenomegaly
The common complications of CNL include:<ref name="ElliottHanson2004">{{cite journal|last1=Elliott|first1=M A|last2=Hanson|first2=C A|last3=Dewald|first3=G W|last4=Smoley|first4=S A|last5=Lasho|first5=T L|last6=Tefferi|first6=A|title=WHO-defined chronic neutrophilic leukemia: a long-term analysis of 12 cases and a critical review of the literature|journal=Leukemia|volume=19|issue=2|year=2004|pages=313–317|issn=0887-6924|doi=10.1038/sj.leu.2403562}}</ref><ref name="CigudosaMenezes2015">{{cite journal|last1=Cigudosa|first1=Juan C|last2=Menezes|first2=Juliane|title=Chronic neutrophilic leukemia: a clinical perspective|journal=OncoTargets and Therapy|year=2015|pages=2383|issn=1178-6930|doi=10.2147/OTT.S49688}}</ref>
* Predisposing to hemorrhage (intracranial hemorrhage as the most common cause of death in CNL patients) 
* Progression of disease
* Blastic or leukemic conversion
* Treatment-related toxicity
 
The indication of disease progression in CNL patients include:<ref name="DaoTyner2015">{{cite journal|last1=Dao|first1=K.-H. T.|last2=Tyner|first2=J. W.|title=What's different about atypical CML and chronic neutrophilic leukemia?|journal=Hematology|volume=2015|issue=1|year=2015|pages=264–271|issn=1520-4391|doi=10.1182/asheducation-2015.1.264}}</ref>
 
* Treatment-resistant
* Refractory neutrophilia
* Increasing in red blood cells
* Platelet transfusion dependency
* Deterioration of organomegaly
* Blast crisis


==Diagnosis==
==Diagnosis==

Revision as of 14:47, 30 January 2019


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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Homa Najafi, M.D.[2]

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating chronic neutrophilic leukemia from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

The diagnosis of CNL is based on the WHO criteria, which include:[1]

World Health Organization (WHO) Criteria for CNL Diagnosis
1. Peripheral blood White blood cells(WBC) ≥25 × 109/L:
  • Segmented neutrophils plus band forms ≥80% of WBC
  • Neutrophil precursors <10% of WBC
  • Myeloblasts rarely observed
  • Monocyte count <1 × 109/L
  • No dysgranulopoies.
2. Hypercellular bone marrow:
  • Neutrophil granulocytes increased in percentage and number
  • Normal neutrophil maturation
  • Myeloblasts <5% of nucleated cells
3. Not meeting WHO criteria for:
  • BCR-ABL1+ chronic myeloid leukemia,
  • Polycythemia vera
  • Essential thrombocythemia,
  • Primary myelofibrosis
4.No rearrangement of:
  • PDGFRA,
  • PDGFRB,
  • FGFR1,
  • PCM1-JAK2
5.Presence of CSF3RT618I or other activating CSF3R mutation or

In the absence of a CSFR3R mutation, persistent neutrophilia (at least 3 months), splenomegaly, and no identifiable cause of reactive neutrophilia

including the absence of a plasma cell neoplasm or, if present, demonstration of clonality of myeloid cells by cytogenetic or molecular studies.

History and Symptoms

The majority of patients with CNL are asymptomatic.

Common symptoms of CNL patients include following:[2][3]

  • Fatigue (as a most common symptom)
  • Weight loss
  • Night sweats
  • Bone pain
  • Easy bruising
  • Pruritus
  • Gout

Physical Examination

Physical examinations of patients with CNL include:[4]

  • Splenomegaly
  • Hepatomegaly
  • Lymphadenopathy(uncommon)

Laboratory Findings

A chronic elevated concentration of blood mature neutrophils is diagnostic for CNL.[4]

Some patients with CNL may have:[3][4][5]

  • Mild anemia
  • Thrombocytopenia
  • Elevation of lactate dehydrogenase (LDH)
  • Elevation of vitamin B12

Other Diagnostic Studies

Bone marrow morphology

Bone marrow morphology in CNL patient may show:[6][7]

  • Hypercellularity with myeloid hyperplasia
  • Increasing myeloid to erythroid ratio
  • Increasing of myelocytes, metamyelocytes, and bands
  • Absence of basophilia and eosinophilia
  • Megakaryocytic hyperplasia

[Diagnostic study] may be helpful in the diagnosis of [disease name]. Findings suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

Other diagnostic studies for [disease name] include [diagnostic study 1], which demonstrates [finding 1], [finding 2], and [finding 3], and [diagnostic study 2], which demonstrates [finding 1], [finding 2], and [finding 3].

Treatment

Medical Therapy

There is no established treatment for patients with CNL. However, following options may be useful in treatment of patients with CNL:[4][8][9]

  • Hematopoitic stem cell transplant (HSCT)
  • Hydroxyurea
  • Interferon
  • Hypomethylating agents
  • Ruxolitinib
  • Thalidomide
  • Cladribine
  • Imatinib
  • Splenic irradiation and splenectomy

References

  1. Arber, D. A.; Orazi, A.; Hasserjian, R.; Thiele, J.; Borowitz, M. J.; Le Beau, M. M.; Bloomfield, C. D.; Cazzola, M.; Vardiman, J. W. (2016). "The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia". Blood. 127 (20): 2391–2405. doi:10.1182/blood-2016-03-643544. ISSN 0006-4971.
  2. Reilly JT (2002). "Chronic neutrophilic leukaemia: a distinct clinical entity?". Br J Haematol. 116 (1): 10–8. PMID 11841395.
  3. 3.0 3.1 Hasle, Henrik; Olesen, Gitte; Kerndrup, GITTE; Philip, Preben; Jacobsen, Niels (1996). "Chronic neutrophil leukaemia in adolescence and young adulthood". British Journal of Haematology. 94 (4): 628–630. doi:10.1046/j.1365-2141.1996.7082329.x. ISSN 0007-1048.
  4. 4.0 4.1 4.2 4.3 Elliott, M A; Hanson, C A; Dewald, G W; Smoley, S A; Lasho, T L; Tefferi, A (2004). "WHO-defined chronic neutrophilic leukemia: a long-term analysis of 12 cases and a critical review of the literature". Leukemia. 19 (2): 313–317. doi:10.1038/sj.leu.2403562. ISSN 0887-6924.
  5. Elliott, Michelle A. (2006). "Chronic neutrophilic leukemia and chronic myelomonocytic leukemia: WHO defined". Best Practice & Research Clinical Haematology. 19 (3): 571–593. doi:10.1016/j.beha.2005.07.012. ISSN 1521-6926.
  6. Uppal, Guldeep; Gong, Jerald (2015). "Chronic neutrophilic leukaemia". Journal of Clinical Pathology. 68 (9): 680–684. doi:10.1136/jclinpath-2015-203060. ISSN 0021-9746.
  7. Swerdlow, Steven (2008). WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon, France: International Agency for Research on Cancer. ISBN 9789283224310.
  8. Szuber, Natasha; Tefferi, Ayalew (2018). "Chronic neutrophilic leukemia: new science and new diagnostic criteria". Blood Cancer Journal. 8 (2). doi:10.1038/s41408-018-0049-8. ISSN 2044-5385.
  9. You W, Weisbrot IM (1979). "Chronic neutrophilic leukemia. Report of two cases and review of the literature". Am J Clin Pathol. 72 (2): 233–42. PMID 289288.