Chronic neutrophilic leukemia

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Homa Najafi, M.D.[2]; Grammar Reviewer: Natalie Harpenau, B.S.[3]

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. CSF3R mutations are seen in most patient and is responsible for pathogenesis of CNL patients. World health organization (WHO) introduces criteria for the diagnosis of chronic neutrophilic leukemia (CNL) that are based on the laboratory finding of peripheral blood cells, bone marrow, cytogenic mutation, and differential diagnosis. There is no treatment for chronic neutrophilic leukemia (CNL). Although, hematopoitic stem cell transplant, hydroxyurea, interferon, hypomethylating agents, ruxolitinib, thalidomide, cladribine, imatinib, splenic irradiation and splenectomy are some options that are used in patients with CNL. There is no treatment for chronic neutrophilic leukemia (CNL). Although, hematopoitic stem cell transplant, hydroxyurea, interferon, hypomethylating agents, ruxolitinib, thalidomide, cladribine, imatinib, splenic irradiation and splenectomy are some options that are used in patients with CNL.

Chronic neutrophilic leukemia(CNL) was first presented by Tuohy, in a case of splenomegaly and neutrophilic leukocytosis, in 1920. Although, It was named by Tanzer et al, in 1964. WHO introduced the criteria for the diagnosis of this disease as a myeloproliferative disorder in 2001. In 2013, CSF3R (colony stimulating factor 3 receptor) mutations was proposed that was found in the most CNL patients and made a huge change in diagnosis and treatment of this patient.

There is no established system for the classification of chronic neutrophilic leukemia (CNL).

The exact pathogenesis of Chronic neutrophilic leukemia (CNL) is not fully understood. Some cytogenic abnormalities like trisomy 7,8,9,21, deletion 11q, 20q6,7 may be seen in CNL patients. The mutation of CSF3R is seen in most patients. Moreover of mutation in CSF3R, there are some other genetic mutations which are less common. Polycythemia vera, plasma cell disorders and nephrotic syndrome can be associated with CNL.

The etiology of Chronic neutrophilic leukemia (CNL) is unknown.

Chronic neutrophilic leukemia (CNL) must be differentiated from other diseases that cause weight loss, night sweats, hepatosplenomegaly, and palpable lymph nodes and neutrophilia.

Chronic neutrophilic leukemia is an extremely rare disease. There are almost only 200 patients with CNL worldwide. The exact incidence of CNL is undetermined.

The median age at diagnosis is 66.5 years and the incidence of disease increases with age. There is no racial predilection to CNL and it affects men and women almost equally.

Chronic neutrophilic leukemia (CNL) must be differentiated from other diseases that cause weight loss, night sweats, hepatosplenomegaly, and palpable lymph nodes and neutrophilia.

There is insufficient evidence to recommend routine screening for chronic neutrophilic leukemia (CNL).

Course of the disease is variable in CNL patients, developing blast crisis is happened in most patients. Moreover, Progression to acute myeloid leukemia may seen in 10-21.2% of patients with CNL. Common complications of CNL include predisposing to hemorrhage, progression of disease, blastic or leukemic conversion and treatment-related toxicity .Prognosis is generally poor, and the 5-year survival rate of patients with CNL is approximately 28%. Some criteria same as treatment resistance, refractory neutrophilia, increasing in red blood cells, platelet transfusion dependency, deterioration of organomegaly and blast crisis indicate disease progression.

World health organization (WHO) introduces criteria for the diagnosis of chronic neutrophilic leukemia (CNL) that are based on the laboratory finding of peripheral blood cells, bone marrow, cytogenic mutation, and differential diagnosis.

The majority of patients with Chronic neutrophilic leukemia (CNL) are asymptomatic. The most common symptom is fatigue. The other symptoms of CNL include weight loss , night sweats, bone pain, easy bruising, pruritus and gout.

The appearance of patient with chronic neutrphilic leukemia (CNL) is usually normal. Common physical examination findings of Chronic neutrophilic leukemia include splenomegaly, hepatomegaly, fever, petechiae, bruises, lymphadenopathy.

A chronic elevated concentration of blood mature neutrophils is diagnostic for chronic neutrophilic leukemia (CNL). There are other blood, bone marrow and genetic tests which help the diagnosis of CNL.

There are no ECG findings associated with chronic neutrophilic leukemia (CNL).

There are no x-ray findings associated with chronic neutrophilic leukemia (CNL). However, an x-ray may be helpful in the diagnosis of complications of CNL, which include splenomegaly, hepatomegaly, and lymphadenopathy.

There are no ultrasound findings associated with chronic neutrophilic leukemia (CNL). However, an ultrasoundmay be helpful in the diagnosis of complications of CNL, which include splenomegaly, hepatomegaly, and lymphadenopathy.

TThere are no CT scan findings associated with chronic neutrophilic leukemia (CNL). However, an CT scan may be helpful in the diagnosis of complications of CNL, which include splenomegaly, hepatomegaly, and lymphadenopathy.

There are no MRI findings associated with chronic neutrophilic leukemia (CNL). However, an MRI may be helpful in the diagnosis of complications of CNL, which include splenomegaly, hepatomegaly, and lymphadenopathy.

There are no other imaging findings associated with chronic neutrophilic leukemia (CNL).

Bone marrow morphology may be helpful in the diagnosis of chronic neutrophilic leukemia (CNL). Hypercellularity with myeloid hyperplasia, increasing myeloid to erythroid ratio, increasing of myelocytes, metamyelocytes, and bands, absence of basophilia and eosinophilia,Megakaryocytic hyperplasia

There is no standard medical treatment for chronic neutrophilic leukemia (CNL). Although, Hydroxyurea, Ruxolitinib, Interferon, Thalidomide, Cladribine and Imatinib are some options that are used in patients with CNL.

Splenectomy was used as a palliative treatment in patients of chronic neutrophilic leukemia (CNL) with splenomegaly. Although, because of neutrophilia was became worse in some reports, it’s not recommended anymore.

Hematopoitic stem cell transplant is the mainstay of treatment for CNL patients. It is recommended that every patients that are qualified for HSCT, take this treatment. Since, the therapy in blast phases has the poor outcomes, HSCT should be started as soon as possible in the disease course, before blast transformation. Splenic irradiation was used as a palliative treatment in patients of CNL with splenomegaly.

There are no established measures for the primary prevention of chronic neutrophilic leukemia (CNL).

There are no established measures for the secondary prevention of chronic neutrophilic leukemia (CNL).

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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]; Grammar Reviewer: Natalie Harpenau, B.S.[3]

Chronic neutrophilic leukemia(CNL) was first presented by Tuohy, in a case of splenomegaly and neutrophilic leukocytosis, in 1920. Although, It was named by Tanzer et al, in 1964. WHO introduced the criteria for the diagnosis of this disease as a myeloproliferative disorder in 2001. In 2013, CSF3R (colony stimulating factor 3 receptor) mutations was proposed that was found in the most CNL patients and made a huge change in diagnosis and treatment of this patient.

• In 1920, Tuohy described the first case of CNL with severe splenomegaly and neutrophilic leukocytosis as a unique disease. However, it was named for the fist time as CNL by Tanzer et al, in 1964.^[1][2]
• In 2001, WHO introduced the criteria for diagnosis CNL as a myeloproliferative disorder that was revised in 2016.^[3]
• In 2013, CSF3R (colony stimulating factor 3 receptor) mutations was proposed that was found in the most CNL patients.^[4]

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

There is no established system for the classification of chronic neutrophilic leukemia (CNL).

There is no established system for the classification of CNL.

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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]; Grammar Reviewer: Natalie Harpenau, B.S.[3]

The exact pathogenesis of Chronic neutrophilic leukemia (CNL) is not fully understood. Some cytogenic abnormalities like trisomy 7,8,9,21, deletion 11q, 20q6,7 may be seen in CNL patients. The mutation of CSF3R is seen in most patients. Moreover of mutation in CSF3R, there are some other genetic mutations which are less common.Polycythemia vera, plasma cell disorders and nephrotic syndrome can be associated with CNL.

• It is understood that clonality has a role in the pathogenesis of CNL. Cytogenetic abnormalities were seen in the diagnostic time or blast transformation in patients with CNL. Finding of these cytogenetic abnormalities were recommended that monoclonality involved in the pathogenesis of CNL.^[1][2]

• The cytogenetic abnormalities may be seen in CNL patients are:^{[3][4][5][6][7][8][9]}
  • Specific ones:
    • Trisomy 8
    • Trisomy 21
    • Deletion 11q
    • Deletion 20q6
  • non-specific ones:
    • Deletion Y
    • Trisomy 7
    • Trisomy 9
    • Detection of JAK2V617F

• The progression to CNL usually involves the CSF3R mutation. CSF3R encodes the receptor of CSF3 . It activates some pathways such as the Janus-associated kinase (JAK)/signal transducer and activator of transcription (STAT) pathway and so CSF3 acts as a neutrophilic growth factor. This mutation causes autonomous cell proliferation. CSF3RT618I and CSF3RT615A are the two types of membrane-proximal CSF3R mutations which are the most common ones. These two types activate the JAK2/STAT3 signaling pathway which is inhibited by Ruxolitinib. The other less common mutations such as truncation CSF3R mutations initiate SRC family tyrosine kinase nonreceptor 2 (TNK2 kinases) pathway and the inhibitor of this pathway is Dasatinib.^{[10][11][12][13][14][15]}

The development of CNL is the result of multiple genetic mutations such as:^{[16][3][15][17][18][19][20]}

• CSF3R
• SETBP1
• ASXL1
• TET2
• EZH2
• KDM6A

Conditions associated with CNL include:^{[21][22][23][24][25][26]}

• Polycythemia vera
• Plasma cell disorders:
  • Multiple myeloma
  • Monoclonal gammopathy of undetermined significance
  • Plasmacytoma
• Nephrotic syndrome

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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]

The etiology of Chronic neutrophilic leukemia (CNL) is unknown.

The etiology of CNL is currently unknown.

Template:WikiDoc Sources

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hannan Javed, M.D.[2], Zahir Ali Shaikh, MD[3], Homa Najafi, M.D.[4]; Grammar Reviewer: Natalie Harpenau, B.S.[5]

Chronic neutrophilic leukemia (CNL) must be differentiated from other diseases that cause weight loss, night sweats, hepatosplenomegaly, and palpable lymph nodes and neutrophilia.

ABBREVIATIONS

N/A: Not available, NL: Normal, FISH: Fluorescence in situ hybridization, PCR: Polymerase chain reaction, LDH: Lactate dehydrogenase, PUD: Peptic ulcer disease, EPO: Erythropoietin, LFTs: Liver function tests, RFTs: Renal function tests, LAP: Leukocyte alkaline phosphatase, LAD: Leukocyte alkaline dehydrgenase, WBCs: White blood cells.

Myeloproliferative neoplasms (MPN)		Clinical manifestations		Diagnosis											Other features
		Symptoms	Physical examination	CBC & Peripheral smear									Bone marrow biopsy	Other investigations
				WBCs							Hb	Plat- elets
				Leuko-cytes	Blasts	Left shift	Baso- phils	Eosino- phils	Mono- cytes	Others
Chronic neutrophilic leukemia (CNL)[1][2][3]		Asymptomatic Constitutional symptoms Bleeding Infection	Splenomegaly Heptomegaly Purpura Anemia related	↑	Minimal	+	NL	NL	NL	↑ LDH ↑ B12 levels	↓	↓	Uniforme and intense hypercellularity with minimal to none fibrosis Neutrophil toxic granulations and Dohle bodies	FISH Imaging for hepatosplenomegaly	Associationed with polycythemia vera and plasma cell disorders Leukocytosis with chronic neutrophilia
Chronic myeloid leukemia (CML), BCR-ABL1+[4][5]		Asymptomatic Constitutional Hyperviscosity and/or anemia related Bleeding Infection	Splenomegaly (46–76%) Purpura Anemia related Priapism	↑	<2%	+	↑	↑	↑	N/A	↓	NL	Hypercellurarity with ↑ granuloscytosis and ↓ erythrocytosis Fibrosis	FISH for t(9;22)(q34;q11.2) Reverse transcriptase quantitative PCR (RQ-PCR) for BCR-ABL	Granulocytic dysplasia is minimal/absent May present with blast crisis Absolute leukocytosis (median of 100,000/µL) Classic myelocyte bulge thrombocytopenia indicates advanced stage
Polycythemia vera (PV)[6][7][8][9]		Constitutional Thromboembolism and bleeding Pruritus after a warm bath PUD related	Facial ruddiness Related to underlying cause Splenomegaly Renal bruit	NL or ↑	None	–	↑ or ↓	NL or ↑	NL	↓ Serum ferritin ↓ Folate levels ↑↑ B12 levels	↑↑	NL	Hypercellularity for age with tri-lineage growth Myelofibrosis (in up to 20% of patients)	Radioisotope studies Serum EPO levels LFTs RFTs Imaging studies	May transform into myelofibrosis or leukemia
Primary myelofibrosis (PMF)[10][11][12][13]		Constitutional Anemia related Bleeding Infection Abdominal Pain	Hepatosplenomegaly Petechiae & ecchymoses Abdominal distension Lymphadenopathy	↓	Erythroblasts	–	Absent	NL	NL	↑ LAP ↑ LAD ↑ Uric acid ↑ B12 levels	↓	↓	Variable with fibrosis or hypercellularity	JAK2 mutation CALR mutation MPL mutation	Bone marrow aspiration shows a dry tap Variable with leukocytosis or leukopenia
Essential thrombocythemia (ET)[14][15][16]		Headache Dizziness Visual disturbances Priapism Acute chest pain	Splenomegaly Skin bruises	NL or ↑	None	–	↓ or absent	NL	NL	N/A	↓	↑↑	Normal/Hypercellular	JAK2 mutation CALR mutation MPL mutation	Thrombosis Hemorrhage Pregnancy loss
Chronic eosinophilic leukemia, not otherwise specified (NOS)[17][18][19][20]		Constitutional Rash Rhinitis Gastritis Thromboembolism related	Hypertension Eczema, mucosal ulcers, erythema Angioedema Ataxia Anemia Lymphadenopathy Hepatosplenomegaly	↑	Present	+	↑	↑↑	↑	↑ B12 levels ↑ LDH	↓	↓	Hypercelluar with ↑ eosinophilic precursors, ↑ eosinophils, and atypical mononuclear cells	FISH Cytogenetic analysis of purified eosinophils and X-chromosome inactivation analysis	Heart failure Lung fibrosis Encephalopathy Erythema annulare centrifugam
MPN, unclassifiable		Similar to other myeloproliferative neoplasms	Similar to other myeloproliferative neoplasms	↑	Variable	±	↑ or ↓	↑ or ↓	↑ or ↓	May resemble other myeloproliferative neoplasms	↓	↑	↑ megakaryocyte proliferation with variable hypercellularity in granulocytic or erythrocytic cell lines	N/A	Similar to other myeloprolifeartive neoplasms but do not fulfil the criteria to be classified to a specific type
Mastocytosis[21][22][23][24]		Constitutional Pruritus & Flushing Urticaria & Blisters Hypotension & PUD Bleeding Bronchoconstriction	Mastocytosis exanthema Blistering Swelling Lymphadenopathy Bleeding Fibrosis	↑	None	–	NL	↑	NL	↑ Alkaline phosphatase ↑ LDH	↓	↓ or ↑	Multifocal dense infiltrates of mast cells with atypical morphology in >25 %	Cytogenetic analysis for c-KIT receptor mutations Serum tryptase levels 24-hour urine test for N-methyl histamine and 11-beta-prostaglandine	Skin most commonly involved Susceptibility to anaphylaxix Osteoporosis
Myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1, or with PCM1–JAK2[25][26][27][28]		Asymptomatic Constitutional Rash Cough & breathlessness Peripheral neuropathy/ encephalopathy	Fever Lymphadenopathy	↑	NL	–	NL	↑	↑	None	NL	↓	Myeloid expansion with eosinophilia	FISH shows t(8;13) and t(8;22)	May present or evolve into acute myeloid or lymphoblastic leukemia Leukocytosis (30 – 59 × 109/L
B-lymphoblastic leukemia/lymphoma[29][30]		Constitutional Anemia related Bleeding Infection Bone pain	Pallor Petechiae Organomegaly Lymphadenopathy	NL or ↑	>25%	N/A	↑ or ↓	↑ or ↓	↑ or ↓	Auer bodies	↓	↓	Hypercellular with blast infilterationwith or without myelodysplasia	Cytogenetic analysis Flow cytometry FISH	May present as extramedullary disease (Myeloid sarcoma)
Myelodysplastic syndromes (MDS)[31][32]		Constitutional Anemia related Bleeding Infection	Pallor Petechiae Organomegaly	↓	Variable	–	↓	↓	↓	Macro-ovalocytes Basophilic stippling Howell-Jolly body	↓	↓	Hypercellular/ normocellular bone marrow with dysplastic changes	Cytogenetic analysis Flow cytometry	Leukemia transformation Acquired pseudo-Pelger-Huët anomaly
Acute myeloid leukemia (AML) and related neoplasms[33][34]		Constitutional Anemia related Bleeding Bone pain Joint pain Infections	Infection related Pallor Leukemia cutis Bruising & petechiae Lymphadenopathy Hepatosplenomegaly	NL or ↑	↑	N/A	↑ or ↓	↑ or ↓	↑ or ↓	↑ Potassium ↑ Uric acid ↑ Phosphorus ↓ Calcium ↑ LDH	↓	↓	Increased immaturemyeloid cells with dysplasia	Cytogenetic analysis Flow cytometry FISH	Common in Down syndrome
Blastic plasmacytoid dendritic cell neoplasm[35][36][37][38]		Cutaneous symptoms (brown/purple nodular lesions) on face, scalp, lower limb & trunk	Brown/violaceous bruise like lesions Lymphadenopathy Splenomegaly	NL	↑		NL	NL	NL	Neutropenia	↓	↓	Malignant cells	Immunohistochemistry or flow cytometry for CD4 & CD56	TdT expression positive May develop chronic myelomonocytic leukemia (CMML)
Myelodysplastic /myeloproliferative neoplasms (MDS/MPN)	Chronic myelomonocytic leukemia (CMML)[39] [40][41]	Constitutional Anemia related Bleeding Infections Bone pain Leukemia Cutis	Organomegaly Bruising	↑	< 20%		NL	↑	↑↑	↑ LDH	↓	↓	Myelodysplastic and myeloproliferative feature	Cytogenetic analysis Flow cytometry	Overlapping of both, MDS and MPN Absolute monocytosis > 1 × 109/L (defining feature) MD-CMML:WBC ≤ 13 × 109/L (FAB)  MP-CMML:WBC > 13 × 109/L (FAB)
	Atypical chronic myeloid leukemia (aCML), BCR-ABL1-[42][43]	Asymptomatic Constitutional Hyperviscosity and/or anemia related Bleeding Infection	Splenomegaly (46–76%) Purpura Anemia related Priapism	↑	<20%	+	<2% of WBCs	N/A	N/A	N/A	↓	↓	Granulocytic hyperplasia with prominent dysplasia	Cytogenetic analysis Flow cytometry	Granulocytic dysplasia is prominent Absence of BCR-ABL or PDGFRA, PDGFRB, or FGFR1 rearrangements WBC > 13 × 109/L
	Juvenile myelomonocytic leukemia (JMML)[44][45]	Infections Anemia related	Hepatosplenomegaly Lymphadenopathy Rash	↑	↑	N/A	N/A	N/A	↑	↓ Serum Iron ↑ B12 levels	↓	↓	Hypercelluar with ↑ myeloid cells in stages of maturation	Cytogenetic analysis Flow cytometry	Polyclonal hypergammaglobulinemia
	MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T)[46][47][48]	Constitutional Anemia related Thrombosis	Variable	NL or ↑	NL	–	NL	N/A	N/A	↑ Serum Iron	↓	↑	Hypercellularity with dyserythropoiesis and increased megakaryocytes	Cytogenetic analysis Flow cytometry	Large atypical megakaryocytes Ringed sideroblasts SF3B1 mutation
T-lymphoblastic leukemia/ lymphoma	T-lymphoblastic leukemia/ lymphoma[49][50][51]	Constitutional Anemia Related Bleeding Superior vena cava syndrome	Lymphadenopathy Mediastinal mass Pleural effusions Tracheal obstruction Pericardial effusions	↑	>25% blasts (Leukemia) <25% blasts (Lymphoma)	±	↑ or ↓	↑ or ↓	↑ or ↓	↑ LDH Positive for TdT	↓	↓	Hypercelluarity with increased T cells precursors	Cytogenetic analysisFlow cytometry FISH	May involve brain, skin, and testes.
	Provisional entity: Natural killer (NK) cell lymphoblastic leukemia/lymph[52]	Constitutional Anemia Related Bleeding Superior vena cava syndrome	Lymphadenopathy Mediastinal mass Pleural effusions Tracheal obstruction Pericardial effusions	↑	↑	±	↑ or ↓	↑ or ↓	↑ or ↓	↑ LDH	↓	↓	N/A	Cytogenetic analysis FISH Flow cytometry	Similar to T-cell lymphoblastic leukemia but may have more aggressive clinical course. Diagnosis is usually based on presence of CD56 expression, and T-cell-associated markers such as CD2 and CD7. B-cell markers are absent.
	Provisional entity: Early T-cell precursor lymphoblastic leukemia[53][54]	Constitutional Anemia Related Bleeding Superior vena cava syndrome	Lymphadenopathy Mediastinal mass Pleural effusions Tracheal obstruction Pericardial effusions	↑	↑	±	↑ or ↓	↑ or ↓	↑ or ↓	↑ LDH	↓	↓	Hypercelluarity with increased T cells precursors	Cytogenetic analysis FISH Flow cytometry	Similar to T-cell lymphoblastic leukemia but is more aggressive clinically and cell are characterized by cytometry as CD1a−, CD8−, CD5− (dim), and positivity for 1 or more stem cell or myeloid antigens. Gene expression indicates more immature cells as compared to other subtypes of T-cell neoplasms.

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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]; Grammar Reviewer: Natalie Harpenau, B.S.[3]

Chronic neutrophilic leukemia is an extremely rare disease. There are almost only 200 patients with CNL worldwide. The exact incidence of CNL is undetermined. The median age at diagnosis is 66.5 years and the incidence of disease increases with age. There is no racial predilection to CNL and it affects men and women almost equally.

• The exact incidence of CNL is undetermined.^[1]

• There are almost only 200 patients with CNL worldwide.^[2]

• The incidence of CNL increases with age; the median age at diagnosis is 66.5 years. ^[3]

• There is no racial predilection to CNL.^[3]

• CNL affects men and women equally.^[3]

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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]

There are no established risk factors for chronic neutrophilic leukemia (CNL).

There are no established risk factors for CNL.

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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]

There is insufficient evidence to recommend routine screening for chronic neutrophilic leukemia (CNL).

There is insufficient evidence to recommend routine screening for CNL.

Template:WH Template:WS

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Homa Najafi, M.D.[2]; Grammar Reviewer: Natalie Harpenau, B.S.[3]

Course of the disease is variable in CNL patients, developing blast crisis is happened in most patients. Moreover, Progression to acute myeloid leukemia may seen in 10-21.2% of patients with CNL. Common complications of CNL include predisposing to hemorrhage, progression of disease, blastic or leukemic conversion and treatment-related toxicity .Prognosis is generally poor, and the 5-year survival rate of patients with CNL is approximately 28%. Some criteria same as treatment resistance, refractory neutrophilia, increasing in red blood cells, platelet transfusion dependency, deterioration of organomegaly and blast crisis indicate disease progression.

• Course of the disease is variable in CNL patients, developing blast crisis is happened in most patients. Moreover, Progression to acute myeloid leukemia may seen in 10-21.2% of patients with CNL.^[1][2][3]

• The common complications of CNL include:^[4][5]
  • 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

• Prognosis is generally poor, and the 5-year survival rate of patients with CNL is approximately 28%.^[3][6]

• The factors that can predict poor outcomes are:^[1][7][8]
  • 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 evidence of disease progression in CNL patients include:^[9]
  • Treatment-resistant
  • Refractory neutrophilia
  • Increasing in red blood cells
  • Platelet transfusion dependency
  • Deterioration of organomegaly
  • Blast crisis

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