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| '''For patient information, click [[Leukemia (patient information)|here]]'''{{Chronic neutrophilic leukemia}} | | '''For patient information, click [[Leukemia (patient information)|here]]'''{{Chronic neutrophilic leukemia}} |
| {{CMG}} {{AE}}[[Homa Najafi , M.D.]] | | {{CMG}}; {{AE}} {{Homa}}; {{GRR}} {{Nat}} |
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| ==Overview==
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| Chronic neutrophilic leukemia (CNL) is an extremely rare myeloproliferative neoplasms with almost 200 cases in the world. While, most of the time this disease is asymptomatic, fatigue, weight loss, night sweats, bone pain, gout and pruritus are some of its symptoms. Splenomegaly is found in examination of most patients.
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| ==Historical Perspective==
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| * Chronic neutrophilic leukemia(CNL) was first presented by Tuohy, in a case of splenomegaly and neutrophilic leukocytosis, in 1920.<ref name="Tuohy1920">{{cite journal|last1=Tuohy|first1=E. L.|title=A CASE OF SPLENOMEGALY WITH POLYMORPHONUCLEAR NEUTROPHIL HYPERLEUKOCYTOSIS|journal=The American Journal of the Medical Sciences|volume=160|issue=1|year=1920|pages=18–24|issn=0002-9629|doi=10.1097/00000441-192007000-00003}}</ref> Although, It was named by Tanzer et al, in 1964.<ref name="TanzerHarel1964">{{cite journal|last1=Tanzer|first1=J.|last2=Harel|first2=P.|last3=Boiron|first3=M.|last4=Bernard|first4=Jean|title=CYTOCHEMICAL AND CYTOGENETIC FINDINGS IN A CASE OF CHRONIC NEUTROPHILIC LEUKÆMIA OF MATURE CELL TYPE|journal=The Lancet|volume=283|issue=7329|year=1964|pages=387–388|issn=01406736|doi=10.1016/S0140-6736(64)92142-7}}</ref>
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| * In 2001, WHO introduced the criteria for diagnosis CNL as a myeloproliferative disorder that was revised in 2016.<ref name="UppalGong2015">{{cite journal|last1=Uppal|first1=Guldeep|last2=Gong|first2=Jerald|title=Chronic neutrophilic leukaemia|journal=Journal of Clinical Pathology|volume=68|issue=9|year=2015|pages=680–684|issn=0021-9746|doi=10.1136/jclinpath-2015-203060}}</ref>
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| * In 2013, CSF3R (colony stimulating factor 3 receptor) mutations was proposed that was found in the most CNL patients.<ref name="MaxsonGotlib2013">{{cite journal|last1=Maxson|first1=Julia E.|last2=Gotlib|first2=Jason|last3=Pollyea|first3=Daniel A.|last4=Fleischman|first4=Angela G.|last5=Agarwal|first5=Anupriya|last6=Eide|first6=Christopher A.|last7=Bottomly|first7=Daniel|last8=Wilmot|first8=Beth|last9=McWeeney|first9=Shannon K.|last10=Tognon|first10=Cristina E.|last11=Pond|first11=J. Blake|last12=Collins|first12=Robert H.|last13=Goueli|first13=Basem|last14=Oh|first14=Stephen T.|last15=Deininger|first15=Michael W.|last16=Chang|first16=Bill H.|last17=Loriaux|first17=Marc M.|last18=Druker|first18=Brian J.|last19=Tyner|first19=Jeffrey W.|title=Oncogenic CSF3R Mutations in Chronic Neutrophilic Leukemia and Atypical CML|journal=New England Journal of Medicine|volume=368|issue=19|year=2013|pages=1781–1790|issn=0028-4793|doi=10.1056/NEJMoa1214514}}</ref>
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| ==Classification==
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| There is no established system for the classification of CNL.
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| ==Pathophysiology==
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| The exact pathogenesis of [disease name] is not fully understood.
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| It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
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| [Pathogen name] is usually transmitted via the [transmission route] route to the human host.
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| Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
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| [Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
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| The progression to [disease name] usually involves the [molecular pathway].
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| The pathophysiology of [disease/malignancy] depends on the histological subtype.
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| ==Causes==
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| Disease name] may be caused by [cause1], [cause2], or [cause3].
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| Common causes of [disease] include [cause1], [cause2], and [cause3].
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| The most common cause of [disease name] is [cause 1]. Less common causes of [disease name] include [cause 2], [cause 3], and [cause 4].
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| The cause of [disease name] has not been identified. To review risk factors for the development of [disease name], click [[Pericarditis causes#Overview|here]].
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| ==Differentiating ((Page name)) from Other Diseases==
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| [Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as [differential dx1], [differential dx2], and [differential dx3].
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| | {{SK}} [[CNL]] |
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| [Disease name] must be differentiated from [[differential dx1], [differential dx2], and [differential dx3]. | | ==[[Chronic neutrophilic leukemia overview|Overview]]== |
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| ==Epidemiology and Demographics== | | ==[[Chronic neutrophilic leukemia historical perspective|Historical Perspective]]== |
| * There are almost only 200 patients with CNL worldwide.<ref>{{cite book | last = Swerdlow | first = Steven | title = WHO classification of tumours of haematopoietic and lymphoid tissues | publisher = International Agency for Research on Cancer | location = Lyon, France | year = 2008 | isbn = 9789283224310 }}</ref>
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| * The exact incidence of CNL is undetermined.<ref name="SzuberTefferi2018">{{cite journal|last1=Szuber|first1=Natasha|last2=Tefferi|first2=Ayalew|title=Chronic neutrophilic leukemia: new science and new diagnostic criteria|journal=Blood Cancer Journal|volume=8|issue=2|year=2018|issn=2044-5385|doi=10.1038/s41408-018-0049-8}}</ref>
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| *The incidence of CNL increases with age; the median age at diagnosis is 66.5 years.
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| *There is no racial predilection to CNL.
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| *CNL affects men and women almost equally.<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>
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| ==Risk Factors== | | ==[[Chronic neutrophilic leukemia classification|Classification]]== |
| There are no established risk factors for [disease name].
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| | ==[[Chronic neutrophilic leukemia pathophysiology|Pathophysiology]]== |
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| The most potent risk factor in the development of [disease name] is [risk factor 1]. Other risk factors include [risk factor 2], [risk factor 3], and [risk factor 4].
| | ==[[Chronic neutrophilic leukemia causes|Causes]]== |
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| | ==[[Chronic neutrophilic leukemia differential diagnosis|Differentiating chronic neutrophilic leukemia from other Diseases]]== |
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| Common risk factors in the development of [disease name] include [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].
| | ==[[Chronic neutrophilic leukemia epidemiology and demographics|Epidemiology and Demographics]]== |
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| | ==[[Chronic neutrophilic leukemia risk factors|Risk Factors]]== |
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| Common risk factors in the development of [disease name] may be occupational, environmental, genetic, and viral.
| | ==[[Chronic neutrophilic leukemia screening|Screening]]== |
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| ==Screening== | | ==[[Chronic neutrophilic leukemia natural history, compilications and prognosis|Natural History, Complications and Prognosis]]== |
| There is insufficient evidence to recommend routine screening for [disease/malignancy].
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| According to the [guideline name], screening for [disease name] is not recommended.
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| According to the [guideline name], screening for [disease name] by [test 1] is recommended every [duration] among patients with [condition 1], [condition 2], and [condition 3].
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| ==Natural History, Complications, and Prognosis==
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| If left untreated, 10-21.2% of patients with CNL may progress to develop acute myeloid leukemia (AML).<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>
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| Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
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| 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
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| | author = [[J. Bohm]] & [[H. E. Schaefer]]
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| | title = Chronic neutrophilic leukaemia: 14 new cases of an uncommon myeloproliferative disease
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| | journal = [[Journal of clinical pathology]]
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| | volume = 55
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| | issue = 11
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| | pages = 862–864
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| | year = 2002
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| | month = November
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| | pmid = 12401827
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| }}</ref>
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| 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>
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| <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>
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| * white blood cell count>50,000 cells per microliter
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| * ASXL1 mutation
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| * Thrombocytopenia
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| The transformation rate to acute myeloid leukemia (AML) has been shown to vary between 10% and 21.2%6,16 with a median time to AML transformation of 21 months (3–94 months)89,158.The spectrum of fatal complications in CNL includes hemorrhagic diathesis, with fatal intracranial hemorrhage being particularly common in earlier reports11, progressive disease, blastic or leukemic transformation, and treatment-related toxicity following chemotherapy induction or transplantation12,158. Distinct disease phases analogous to the accelerated and blastic phases observed in CML have not formally been defined in CNL, though its natural history often does recapitulate that of untreated CML. Disease progression in CNL typically involves resistance to treatment, progressive refractory neutrophilia, increasing red cell and platelet transfusion dependency, worsening organomegaly consistent with disease acceleration, and eventual blast crisis which to date, has been exclusively reported as myeloid. As discussed, such progression may be associated with the acquisition of additional cytogenetic abnormalities148.Further, as in other classic MPN, there appears to be the potential to evolve toward/from other MPNs such as PV50,51 and CMML18.
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| There is no validated prognostic system for CNL and aCML. Recently, in small series, some features predicted worse outcome, including white blood cell count (WBC) of > 50,000 cells per microliter in CNL [46] and a combination of features based on multivariable analysis in aCML including age > 67 years, hemoglobin < 10 g/dL, and TET2 mutations (each counted as one risk factor [50]). A multivariable analysis found that ASXL1 mutations and thrombocytopenia independently predicted shortened survival in CNL [47•]. In most studies, ASXL1 and SETBP1 mutations are considered negative prognosticators in CNL and aCML (reviewed in [1••, 64•]). In one meta-analysis, SETBP1 mutation had no significant effect on median overall survival in CNL but had a negative impact on median overall survival in MDS and
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| ==Diagnosis== | | ==Diagnosis== |
| ===Diagnostic Study of Choice===
| | [[Chronic neutrophilic leukemia diagnostic study of choice|Diagnostic study of choice]] | [[Chronic neutrophilic leukemia history and symptoms|History and Symptoms]] | [[Chronic neutrophilic leukemia physical examination|Physical Examination]] | [[Chronic neutrophilic leukemia laboratory findings|Laboratory Findings]] | [[Chronic neutrophilic leukemia electrocardiogram|Electrocardiogram]] | [[Chronic neutrophilic leukemia x ray|X-Ray Findings]] | [[Chronic neutrophilic leukemia echocardiography and ultrasound|Ultrasound]] | [[Chronic neutrophilic leukemia CT|CT-Scan Findings]] | [[Chronic neutrophilic leukemia MRI|MRI Findings]] | [[Chronic neutrophilic leukemia other imaging findings|Other Imaging Findings]] | [[Chronic neutrophilic leukemia other diagnostic studies|Other Diagnostic Studies]] |
| The diagnosis of CNL is based on the WHO criteria, which include:<ref name="ArberOrazi2016">{{cite journal|last1=Arber|first1=D. A.|last2=Orazi|first2=A.|last3=Hasserjian|first3=R.|last4=Thiele|first4=J.|last5=Borowitz|first5=M. J.|last6=Le Beau|first6=M. M.|last7=Bloomfield|first7=C. D.|last8=Cazzola|first8=M.|last9=Vardiman|first9=J. W.|title=The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia|journal=Blood|volume=127|issue=20|year=2016|pages=2391–2405|issn=0006-4971|doi=10.1182/blood-2016-03-643544}}</ref>
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| {| class="wikitable"
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| ! colspan="2" style="background: #4479BA; color: #FFFFFF; text-align: center;" |World Health Organization (WHO) Criteria for CNL Diagnosis
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| ! style="background: #DCDCDC; text-align: center;" |1. Peripheral blood White blood cells(WBC) ≥25 × 109/L:
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| * Segmented neutrophils plus band forms ≥80% of WBC
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| * Neutrophil precursors <10% of WBC
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| * Myeloblasts rarely observed
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| * Monocyte count <1 × 109/L
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| * No dysgranulopoies.
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| ! style="background: #DCDCDC; text-align: center;" |2. Hypercellular bone marrow:
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| * Neutrophil granulocytes increased in percentage and number
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| * Normal neutrophil maturation
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| * Myeloblasts <5% of nucleated cells
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| ! style="background: #DCDCDC; text-align: center;" |3. Not meeting WHO criteria for:
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| * BCR-ABL1+ chronic myeloid leukemia,
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| * Polycythemia vera
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| * Essential thrombocythemia,
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| * Primary myelofibrosis
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| ! style="background: #DCDCDC; text-align: center;" |4.No rearrangement of:
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| * PDGFRA,
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| * PDGFRB,
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| * FGFR1,
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| * PCM1-JAK2
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| ! colspan="2" |5.Presence of CSF3RT618I or other activating CSF3R mutation or
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| In the absence of a CSFR3R mutation, persistent neutrophilia (at least 3 months), splenomegaly, and no identifiable cause of reactive neutrophilia
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| including absence of a plasma cell neoplasm or, if present, demonstration of clonality of myeloid cells by cytogenetic or molecular studies.
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| |} | |
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| ===History and Symptoms===
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| The majority of patients with CNL are asymptomatic.
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| Common symptoms of CNL patients include following:<ref name="pmid11841395">{{cite journal| author=Reilly JT| title=Chronic neutrophilic leukaemia: a distinct clinical entity? | journal=Br J Haematol | year= 2002 | volume= 116 | issue= 1 | pages= 10-8 | pmid=11841395 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11841395 }} </ref><ref name="HasleOlesen1996">{{cite journal|last1=Hasle|first1=Henrik|last2=Olesen|first2=Gitte|last3=Kerndrup|first3=GITTE|last4=Philip|first4=Preben|last5=Jacobsen|first5=Niels|title=Chronic neutrophil leukaemia in adolescence and young adulthood|journal=British Journal of Haematology|volume=94|issue=4|year=1996|pages=628–630|issn=0007-1048|doi=10.1046/j.1365-2141.1996.7082329.x}}</ref>
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| *[[Fatigue (medical)|Fatigue]] (as a most common symptom)
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| *Weight loss
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| *Night sweats
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| *Bone pain
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| *Easy bruising
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| *Pruritus
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| *Gout
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| ===Physical Examination===
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| Physical examinations of patients with 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>
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| *Splenomegaly
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| *Hepatomegaly
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| *Lymphadenopathy(uncommon)
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| ===Laboratory Findings===
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| A chronic elevated concentration of blood mature neutrophils is diagnostic for CNL.<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>
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| Some patients with CNL may have:<ref name="HasleOlesen1996">{{cite journal|last1=Hasle|first1=Henrik|last2=Olesen|first2=Gitte|last3=Kerndrup|first3=GITTE|last4=Philip|first4=Preben|last5=Jacobsen|first5=Niels|title=Chronic neutrophil leukaemia in adolescence and young adulthood|journal=British Journal of Haematology|volume=94|issue=4|year=1996|pages=628–630|issn=0007-1048|doi=10.1046/j.1365-2141.1996.7082329.x}}</ref><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="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>
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| *Mild anemia
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| *Thrombocytopenia
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| *Elevation of lactate dehydrogenase (LDH)
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| *Elevation of vitamin B12
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| ===Other Diagnostic Studies===
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| ===Bone marrow morphology===
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| Bone marrow morphology in CNL patient may show:<ref name="UppalGong2015">{{cite journal|last1=Uppal|first1=Guldeep|last2=Gong|first2=Jerald|title=Chronic neutrophilic leukaemia|journal=Journal of Clinical Pathology|volume=68|issue=9|year=2015|pages=680–684|issn=0021-9746|doi=10.1136/jclinpath-2015-203060}}</ref><ref>{{cite book | last = Swerdlow | first = Steven | title = WHO classification of tumours of haematopoietic and lymphoid tissues | publisher = International Agency for Research on Cancer | location = Lyon, France | year = 2008 | isbn = 9789283224310 }}</ref>
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| *Hypercellularity with myeloid hyperplasia
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| *Increasing myeloid to erythroid ratio
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| *Increasing of myelocytes, metamyelocytes, and bands
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| *Absence of basophilia and eosinophilia
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| *Megakaryocytic hyperplasia
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| [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]. | |
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| 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]. | |
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| ==Treatment== | | ==Treatment== |
| ===Medical Therapy===
| | [[Chronic neutrophilic leukemia medical therapy|Medical Therapy]] | [[Chronic neutrophilic leukemia interventions|Interventions]] | [[Chronic neutrophilic leukemia surgery|Surgery]] | [[Chronic neutrophilic leukemia primary prevention|Primary Prevention]] | [[Chronic neutrophilic leukemia secondary prevention|Secondary Prevention]] | [[Chronic neutrophilic leukemia cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Chronic neutrophilic leukemia future or investigational therapies|Future or Investigational Therapies]] |
| There is no established treatment for patients with CNL. However, following options may be useful in treatment of patients with CNL:<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="SzuberTefferi2018">{{cite journal|last1=Szuber|first1=Natasha|last2=Tefferi|first2=Ayalew|title=Chronic neutrophilic leukemia: new science and new diagnostic criteria|journal=Blood Cancer Journal|volume=8|issue=2|year=2018|issn=2044-5385|doi=10.1038/s41408-018-0049-8}}</ref><ref name="pmid289288">{{cite journal| author=You W, Weisbrot IM| title=Chronic neutrophilic leukemia. Report of two cases and review of the literature. | journal=Am J Clin Pathol | year= 1979 | volume= 72 | issue= 2 | pages= 233-42 | pmid=289288 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=289288 }} </ref>
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| *Hematopoitic stem cell transplant (HSCT)
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| *Hydroxyurea
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| *Interferon
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| *Hypomethylating agents
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| *Ruxolitinib
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| *Thalidomide
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| *Cladribine
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| *Imatinib
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| *Splenic irradiation and splenectomy
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| ==References== | | ==References== |
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| [[Category:Up-To-Date]] | | [[Category:Up-To-Date]] |
| | [[Category:Medicine]] |
| [[Category:Oncology]] | | [[Category:Oncology]] |
| [[Category:Medicine]]
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| [[Category:Hematology]] | | [[Category:Hematology]] |
| [[Category:Immunology]] | | [[Category:Immunology]] |