Chronic neutrophilic leukemia: Difference between revisions
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==Natural History, Complications, and Prognosis== | ==Natural History, Complications, and Prognosis== | ||
If left untreated, | If left untreated, 10-21.2% of patients with CNL may progress to develop acute myeloid leukemia (AML). | ||
OR | OR | ||
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OR | OR | ||
Prognosis is generally | Prognosis is generally poor, and the 5-year survival rate of patients with CNL is approximately 28%. | ||
Though the clinical course of CNL is variable, the overall prognosis is generally reserved with a substantial portion of patients eventually progressing to blast crisis. CNL has been historically described as having a “fatal clinical course”11. Overall median survival has beenreported between 21 and 30 months in earlier reports,with a 5-year survival of 28% in a 2002 review by Reilly6,157. A more recent series of 16 CNL patients, all of whom harbored the CSF3RT618I mutation, demonstrated a median overall survival of 24 months132 which is similar to the median overall survival reported from 40 CNL cases by Elliott et al. (23.5 months)89. Unfortunately recent survival data ominously mirrors that of historical cohorts, showing little to no improvement over time. 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. | |||
==Diagnosis== | ==Diagnosis== | ||
Revision as of 14:46, 9 January 2019
For patient information, click here
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Chronic neutrophilic leukemia Microchapters |
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Differentiating Chronic neutrophilic leukemia from other Diseases |
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Diagnosis |
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Treatment |
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Case Studies |
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Chronic neutrophilic leukemia On the Web |
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American Roentgen Ray Society Images of Chronic neutrophilic leukemia |
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Directions to Hospitals Treating Chronic neutrophilic leukemia |
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Risk calculators and risk factors for Chronic neutrophilic leukemia |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Homa Najafi , M.D.
Overview
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.
Historical Perspective
- Chronic neutrophilic leukemia(CNL) was first presented by Tuohy, in a case of splenomegaly and neutrophilic leukocytosis, in 1920.[1] Although, It was named by Tanzer et al, in 1964.[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]
Classification
There is no established system for the classification of CNL.
Pathophysiology
The exact pathogenesis of [disease name] is not fully understood.
OR
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].
OR
[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
OR
Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
OR
[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
OR
The progression to [disease name] usually involves the [molecular pathway].
OR
The pathophysiology of [disease/malignancy] depends on the histological subtype.
Causes
Disease name] may be caused by [cause1], [cause2], or [cause3].
OR
Common causes of [disease] include [cause1], [cause2], and [cause3].
OR
The most common cause of [disease name] is [cause 1]. Less common causes of [disease name] include [cause 2], [cause 3], and [cause 4].
OR
The cause of [disease name] has not been identified. To review risk factors for the development of [disease name], click here.
Differentiating ((Page name)) from Other Diseases
[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].
OR
[Disease name] must be differentiated from [[differential dx1], [differential dx2], and [differential dx3].
Epidemiology and Demographics
- There are almost only 200 patients with CNL worldwide.[5]
- The exact incidence of CNL is undetermined.[6]
- The incidence of CNL increases with age; the median age at diagnosis is 66.5 years.
- There is no racial predilection to CNL.
- CNL affects men and women almost equally.[7]
Risk Factors
There are no established risk factors for [disease name].
OR
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].
OR
Common risk factors in the development of [disease name] include [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].
OR
Common risk factors in the development of [disease name] may be occupational, environmental, genetic, and viral.
Screening
There is insufficient evidence to recommend routine screening for [disease/malignancy].
OR
According to the [guideline name], screening for [disease name] is not recommended.
OR
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].
Natural History, Complications, and Prognosis
If left untreated, 10-21.2% of patients with CNL may progress to develop acute myeloid leukemia (AML).
OR
Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
OR
Prognosis is generally poor, and the 5-year survival rate of patients with CNL is approximately 28%.
Though the clinical course of CNL is variable, the overall prognosis is generally reserved with a substantial portion of patients eventually progressing to blast crisis. CNL has been historically described as having a “fatal clinical course”11. Overall median survival has beenreported between 21 and 30 months in earlier reports,with a 5-year survival of 28% in a 2002 review by Reilly6,157. A more recent series of 16 CNL patients, all of whom harbored the CSF3RT618I mutation, demonstrated a median overall survival of 24 months132 which is similar to the median overall survival reported from 40 CNL cases by Elliott et al. (23.5 months)89. Unfortunately recent survival data ominously mirrors that of historical cohorts, showing little to no improvement over time. 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.
Diagnosis
Diagnostic Study of Choice
The diagnosis of CNL is based on the WHO criteria, which include:[8]
| World Health Organization (WHO) Criteria for CNL Diagnosis | |
|---|---|
| 1. Peripheral blood White blood cells(WBC) ≥25 × 109/L: |
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| 2. Hypercellular bone marrow: |
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| 3. Not meeting WHO criteria for: |
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| 4.No rearrangement of: |
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| 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 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:[9][10]
- 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:[11]
- Splenomegaly
- Hepatomegaly
- Lymphadenopathy(uncommon)
Laboratory Findings
A chronic elevated concentration of blood mature neutrophils is diagnostic for CNL.[11]
Some patients with CNL may have:[10][11][7]
- 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:[3][12]
- 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:[11][6][13]
- Hematopoitic stem cell transplant (HSCT)
- Hydroxyurea
- Interferon
- Hypomethylating agents
- Ruxolitinib
- Thalidomide
- Cladribine
- Imatinib
- Splenic irradiation and splenectomy
References
- ↑ Tuohy, E. L. (1920). "A CASE OF SPLENOMEGALY WITH POLYMORPHONUCLEAR NEUTROPHIL HYPERLEUKOCYTOSIS". The American Journal of the Medical Sciences. 160 (1): 18–24. doi:10.1097/00000441-192007000-00003. ISSN 0002-9629.
- ↑ Tanzer, J.; Harel, P.; Boiron, M.; Bernard, Jean (1964). "CYTOCHEMICAL AND CYTOGENETIC FINDINGS IN A CASE OF CHRONIC NEUTROPHILIC LEUKÆMIA OF MATURE CELL TYPE". The Lancet. 283 (7329): 387–388. doi:10.1016/S0140-6736(64)92142-7. ISSN 0140-6736.
- ↑ 3.0 3.1 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.
- ↑ Maxson, Julia E.; Gotlib, Jason; Pollyea, Daniel A.; Fleischman, Angela G.; Agarwal, Anupriya; Eide, Christopher A.; Bottomly, Daniel; Wilmot, Beth; McWeeney, Shannon K.; Tognon, Cristina E.; Pond, J. Blake; Collins, Robert H.; Goueli, Basem; Oh, Stephen T.; Deininger, Michael W.; Chang, Bill H.; Loriaux, Marc M.; Druker, Brian J.; Tyner, Jeffrey W. (2013). "Oncogenic CSF3R Mutations in Chronic Neutrophilic Leukemia and Atypical CML". New England Journal of Medicine. 368 (19): 1781–1790. doi:10.1056/NEJMoa1214514. ISSN 0028-4793.
- ↑ Swerdlow, Steven (2008). WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon, France: International Agency for Research on Cancer. ISBN 9789283224310.
- ↑ 6.0 6.1 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.
- ↑ 7.0 7.1 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.
- ↑ 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.
- ↑ Reilly JT (2002). "Chronic neutrophilic leukaemia: a distinct clinical entity?". Br J Haematol. 116 (1): 10–8. PMID 11841395.
- ↑ 10.0 10.1 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.
- ↑ 11.0 11.1 11.2 11.3 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.
- ↑ Swerdlow, Steven (2008). WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon, France: International Agency for Research on Cancer. ISBN 9789283224310.
- ↑ 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.