Chronic neutrophilic leukemia (CNL)
Based on the current guidelines and the current state of research, there are different diagnostic recommendations for patients with chronic neutrophilic leukemia (CNL). We have summarized the most important information on classification and diagnostic methods of chronic neutrophilic leukemia at MLL. In addition, we provide further links about CNL, so that you can inform yourself in more detail.
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Chronic neutrophilic leukemia (CNL): Classification
Chronic neutrophilic leukemia (CNL) is a rare BCR::ABL1-negative myeloproliferative neoplasm that characteristically presents as a triad of persistent neutrophilia, bone marrow hypercellularity, and hepatosplenomegaly. By WHO definition, isolated neutrophilia is a key feature of chronic neutrophilic leukemia that helps differentiate CNL from other chronic myeloid neoplasms (WHO 2022). Thus, compared to CML, CNL is characterized by more mature granulopoietic forms (Szuber et al. 2022).
In 2013, a mutation in the colony stimulating factor 3 receptor (CSF3R) was identified in the majority of chronic neutrophilic leukemia patients studied (Maxson et al. 2013), which is now designated as a defining genomic abnormality by the WHO (WHO 2022).
The diagnosis requires exclusion of reactive neutrophilia and other myeloproliferative and myelodysplastic/myeloproliferative neoplasms. According to WHO 2022, the following criteria serve to establish the diagnosis (WHO 2022):
Table 1: WHO diagnostic criteria in CNL (WHO 2022)
1. |
|
2. |
|
3. |
Not meeting WHO criteria for BCR::ABL1-positive CML, PV, ET oder PMF |
4. |
No evidence of disease-defining gene rearrangements such as PDGFRA, PDGFRB or FGFR1 and no PCM1::JAK2 fusion |
5. |
Presence of CSF3R p.T618I or another activating CSF3R mutation, OR persistent neutrophilia (≥ 3 months), splenomegaly, and no identifiable cause of reactive neutrophilia including absence of a plasma cell neoplasm or, if a plasma cell neoplasm is present, demonstration of clonality of myeloid cells by cytogenetic or molecular studies |
Chronic neutrophilic leukemia (CNL): Diagnostic methods and their significance
Chronic neutrophilic leukemia (CNL): Prognosis
The prognosis of chronic neutrophilic leukemia is variable: disease progression ranges from latent to aggressive (survival from 6 months to > 20 years). Neutrophilia is usually progressive and anemia and thrombocytopenia may follow - if pancytopenia occurs, survival is likely to worsen accordingly. The development of myelodysplastic features may be a sign of transformation to AML (WHO 2022).
Cases with an ASXL1 mutation present have been described as prognostically unfavorable (Elliott et al. 2015, WHO 2022). In contrast, patients with a CSF3R germline mutation appear to have better survival than patients with somatic mutations (Kojima et al. 1999, Druhan et al. 2016, Duployez et al. 2019).
Feature |
Score |
Thrombocytopenia <160*109/L |
2 |
Leukocytosis >60*109/L |
1 |
ASXL1 mutation |
1 |
Legend: 2-4 points = high risk, 0-1 points = low risk.
Chronic neutrophilic leukemia (CNL): Therapy
Due to its
rarity, there is currently no standard therapy for the treatment of chronic neutrophilic leukemia.
Allogeneic stem cell transplantation is the only curative therapeutic option to
date. The development of disease-modifying therapies therefore represents a
major unmet need (Szuber et al. 2022). A treatment algorithm is presented in the new Onkopedia guideline on CNL.
Status: May 2024