HAEM5:Chronic neutrophilic leukaemia: Difference between revisions

[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]]

<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|This page was converted to the new template on 2023-11-30. The original page can be found at [[HAEM4:Chronic Neutrophilic Leukemia (CNL)]].

 

 

[[Myeloproliferative Neoplasms (MPN)|Myeloproliferative Neoplasms]]

 

==Cancer Sub-Classification / Subtype==

 

 

 

Chronic neutrophilic leukemia (CNL) is a rare heterogeneous BCR/ABL1-negative member of the WHO myeloproliferative neoplasm (MPN) category, which presents with neutrophilia lacking dysplastic features.  Diagnostic criteria include sustained increased white blood cells in the peripheral blood for more than 3 months, with a predominance of band and segmented forms equal to or in excess of 25 x10⁹/L.<ref name=":0" />  The bone marrow is hypercellular with elevated myeloid to erythroid ratio, due to increase in neutrophilic granulocyte proliferation, with normal maturation (>80% mature forms of neutrophils and <10% neutrophil precursors) and rare (<5%) of nucleated cells represented by myeloblasts.  This disease is also associated with hepatosplenomegaly, but can affect other tissues.

Diagnosis is made after exclusion of reactive neutrophilia (especially due to plasma cell neoplasms), atypical CML and of other myeloproliferative neoplasms ([[Chronic Myeloid Leukemia (CML), BCR-ABL1 Positive|BCR-ABL1- positive Chronic Myeloid Leukemia]], [[Polycythemia Vera (PV)|Polycythemia Vera]], [[Essential Thrombocythemia (ET)|Essential Thrombocythemia]] and [[Primary Myelofibrosis (PMF)|Primary Myelofibrosis]]) and and myelodysplastic syndrome/myeloproliferative neoplasms.<ref name=":0" /><ref name=":3">{{Cite journal|last=Szuber|first=Natasha|last2=Elliott|first2=Michelle|last3=Tefferi|first3=Ayalew|date=02 2020|title=Chronic neutrophilic leukemia: 2020 update on diagnosis, molecular genetics, prognosis, and management|url=https://pubmed.ncbi.nlm.nih.gov/31769070|journal=American Journal of Hematology|volume=95|issue=2|pages=212–224|doi=10.1002/ajh.25688|issn=1096-8652|pmid=31769070}}</ref><ref name=":4" />  Previous use of G-CSF and leukaemogenic drugs (busulphan, melphalan) must also be excluded.

|'''Signs and Symptoms'''

|EXAMPLE Asymptomatic (incidental finding on complete blood counts)

 

 

 

|'''Laboratory Findings'''

|EXAMPLE Cytopenias

 

!Finding!!Marker

|Positive (universal)||EXAMPLE CD1

|Positive (subset)||EXAMPLE CD2

|-

|Negative (universal)||EXAMPLE CD3

|Negative (subset)||EXAMPLE CD4

|}

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==Chromosomal Rearrangements (Gene Fusions)==

 

 

!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence

!Diagnostic Significance (Yes, No or Unknown)

!Prognostic Significance (Yes, No or Unknown)

|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)

|Yes

|No

|Yes

|EXAMPLE

 

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CNL is by definition Philadelphia chromosome negative (BCR/ABL1-negative).<ref name=":0" />  

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* Gene Mutations (SNV/INDEL)}}

CNL can progress to myeloma or blastic transformation to acute myeloid leukemia.<ref name=":1" />  It can also transform in other forms of MPN (PV or CMML). The presence of ''ASXL1'' as secondary mutation confers worse prognosis.<ref name=":0" /><ref name=":8">{{Cite journal|last=Ma|first=Elliott|last2=A|first2=Pardanani|last3=Ca|first3=Hanson|last4=Tl|first4=Lasho|last5=Cm|first5=Finke|last6=Aa|first6=Belachew|last7=A|first7=Tefferi|date=2015|title=ASXL1 mutations are frequent and prognostically detrimental in CSF3R-mutated chronic neutrophilic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/25850813/|language=en|pmid=25850813}}</ref>

Treatment: There is currently no standard of care or established guidelines for the management of CNL. As such, treatment may involve several therapeutic approaches.<ref name=":3" />  Blood transfusions when necessary, hydroxyurea, allogeneic bone marrow transplantation. Clinical remission has been achieved in instances with long-term interferon α treatment.<ref name=":2" />  Hydroxyurea is the most used therapy, but often requires a second or third line therapy.<ref name=":3" /><ref name=":5" /><ref name=":6" />  Other potential pharmacologic agents include imatinib, ruxolitinib, interferon-alpha(IFN-α), hypomethylating agents, thalidomide, and cladribine.  These may be used in combination.<ref name=":6" /><ref name=":3" /><ref>{{Cite journal|last=Dao|first=Kim-Hien T.|last2=Gotlib|first2=Jason|last3=Deininger|first3=Michael M. N.|last4=Oh|first4=Stephen T.|last5=Cortes|first5=Jorge E.|last6=Collins|first6=Robert H.|last7=Winton|first7=Elliot F.|last8=Parker|first8=Dana R.|last9=Lee|first9=Hyunjung|date=2020-04-01|title=Efficacy of Ruxolitinib in Patients With Chronic Neutrophilic Leukemia and Atypical Chronic Myeloid Leukemia|url=https://pubmed.ncbi.nlm.nih.gov/31880950|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology|volume=38|issue=10|pages=1006–1018|doi=10.1200/JCO.19.00895|issn=1527-7755|pmc=7106977|pmid=31880950}}</ref><ref>{{Cite journal|last=Gunawan|first=Arief S.|last2=McLornan|first2=Donal P.|last3=Wilkins|first3=Bridget|last4=Waghorn|first4=Katherine|last5=Hoade|first5=Yvette|last6=Cross|first6=Nicholas C. P.|last7=Harrison|first7=Claire N.|date=06 2017|title=Ruxolitinib, a potent JAK1/JAK2 inhibitor, induces temporary reductions in the allelic burden of concurrent CSF3R mutations in chronic neutrophilic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/28302714|journal=Haematologica|volume=102|issue=6|pages=e238–e240|doi=10.3324/haematol.2017.163790|issn=1592-8721|pmc=5451352|pmid=28302714}}</ref>  Cases with ''CSF3R'' T618I mutation may respond to treatment with Ruxolitinib (JAK inhibitor) while cases with ''CSF3R'' truncation mutations may be sensitive to Dasatinib (SRC kinase inhibitor).<ref name=":1" />

==Individual Region Genomic Gain / Loss / LOH==

!Chr #!!Gain / Loss / Amp / LOH!!Minimal Region Genomic Coordinates [Genome Build]!!Minimal Region Cytoband

!Diagnostic Significance (Yes, No or Unknown)

!Prognostic Significance (Yes, No or Unknown)

!Therapeutic Significance (Yes, No or Unknown)

!Notes

|EXAMPLE

 

|EXAMPLE Loss

|EXAMPLE

 

chr7:1- 159,335,973 [hg38]

 

|Yes

|Yes

|No

|EXAMPLE

 

Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).

|EXAMPLE

 

|EXAMPLE Gain

|EXAMPLE

 

chr8:1-145,138,636 [hg38]

 

|No

|No

|No

|EXAMPLE

 

Common recurrent secondary finding for t(8;21) (add reference).

==Characteristic Chromosomal Patterns==

!Diagnostic Significance (Yes, No or Unknown)

!Prognostic Significance (Yes, No or Unknown)

!Therapeutic Significance (Yes, No or Unknown)

!Notes

|EXAMPLE

 

|Yes

|EXAMPLE:

 

See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).

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==Gene Mutations (SNV / INDEL)==

!Gene; Genetic Alteration!!'''Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)'''!!'''Prevalence (COSMIC /  TCGA / Other)'''!!'''Concomitant Mutations'''!!'''Mutually Exclusive Mutations'''

!'''Diagnostic Significance (Yes, No or Unknown)'''

!Prognostic Significance (Yes, No or Unknown)

!Therapeutic Significance (Yes, No or Unknown)

!Notes

|EXAMPLE: TP53; Variable LOF mutations

EXAMPLE:

 

EGFR; Exon 20 mutations

 

EXAMPLE: BRAF; Activating mutations

|EXAMPLE: TSG

|EXAMPLE: 20% (COSMIC)

 

EXAMPLE: 30% (add Reference)

|EXAMPLE: IDH1 R123H

|EXAMPLE: EGFR amplification

|}

Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

 

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Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table.'')</span>

|EXAMPLE: BRAF and MAP2K1; Activating mutations

|EXAMPLE: MAPK signaling

|EXAMPLE: Increased cell growth and proliferation

|EXAMPLE: CDKN2A; Inactivating mutations

|EXAMPLE: Cell cycle regulation

|EXAMPLE: Unregulated cell division

|EXAMPLE:  KMT2C and ARID1A; Inactivating mutations

|EXAMPLE:  Histone modification, chromatin remodeling

|EXAMPLE:  Abnormal gene expression program

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