Chronic neutrophilic leukemia C92.7

Chronic neutrophilic leukemia (CNL) is a rare, often aggressive myeloproliferative neoplasm (MPN) characterized by persistent mature neutrophilic leukocytosis, granulocyte hyperplasia in the bone marrow, and frequent hepatosplenomegaly (Szuber N et al 2020).

The disease is very rare and the exact incidence is unknown. To date, < 100 cases have been described.

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The disease usually occurs in older adulthood.

The diagnosis of CNL has usually been made as a diagnosis of exclusion. In 2016, the World Health Organization (WHO) included the presence of activating CSF3R mutations as a key diagnostic feature of CNL. Other criteria include a leukocytosis of ≥25 × 109 /L consisting of >80% neutrophil granulocytes and <10% circulating progenitor cells and rare blasts, and the absence of dysplasia or monocytosis, whereas the criteria for other MPNs are not met (see below).

Thus, the diagnosis can be made based on the presence of certain criteria (Elliott MA et al. 2018):

• Leukocytosis > 25/nl in peripheral blood:
• >80 % of leukocytes are segmental granulocytes.
• <10 % of leukocytes are granulocytic precursors (metamyelocytes, myelocytes, promyelocytes)
• <1 % of the leucocytes are myeloblasts
• hypercellular bone marrow:
• proliferation of neutrophil granulocytes
• <5 % myeloblasts
• no maturation disorders in the neutrophils
• hepatosplenomegaly
• no other reason for neutrophil proliferation:
• no chronic infection or inflammatory disease
• no underlying tumor disease
• no Philadelphia chromosome or BCR-ABL oncogene
• no other myeloproliferative disease(polycythaemia vera, essential thrombocythaemia, primary myelofibrosis)
• no myelodysplastic syndrome, no chronic myelomonocytic leukemia
• Presence of activating CSF3R mutations, most commonly CSF3RT618I. These mutations are primary driver mutations responsible for the characteristic clinical phenotype and potential susceptibility to molecularly targeted therapies (Couto ME et al. 2020; Elliott MA et al. 2018).

There are no therapeutic studies due to the rarity of the disease. The disease can be treated with mild cytoreductive drugs such as hydroxyurea. A therapy trial with interferon alpha is also possible. If a CSF3R mutation is detected, a therapy trial with dasatinib or ruxolitinib is recommended.