Case report: Chronic neutrophilic leukemia associated with monoclonal gammopathies. A case series and review of genetic characteristics and practical management

Abstract

Chronic neutrophilic leukemia (CNL) is a rare but potentially aggressive BCR::ABL1 negative myeloproliferative neoplasm, characterized by sustained mature, neutrophilic leukocytosis. The discovery of key driver mutations in the colony-stimulating-factor-3 receptor (CSF3R) gene resulted in the updated World Health Organization (WHO) diagnostic criteria in 2016. A significant number of CNL cases have been associated with plasma cell dyscrasias, predominantly multiple myeloma (MM) and monoclonal gammopathy of unknown significance (MGUS). Compared to pure CNL, mutated CSF3R is infrequently reported in CNL cases associated with monoclonal gammopathies (MG). Until now it remains unclear whether CNL and occurring plasma cell neoplasms are clonally related or CNL is developing secondary to the underlying dyscrasia. Owing to its rarity, currently no standard of care management exists for CNL and MG-associated CNL. In this case series we report the multi-center experience of five MG-associated CNL cases with a median age of diagnosis of 69 years. Three patients (66%) showed predominance of lambda light chain expression. Four (80%) eventually evolved to MM, and one CNL-MGUS patient developed secondary acute myeloid leukemia (AML). Mutated CSF3R was present in the patient who developed AML but was absent in other cases. To assess possible associated genetic aberrations we performed recurrent analysis with next-generation sequencing (NGS). Two patients (40%) deceased with a median time of survival of 8 years after CNL diagnosis. Three (60%) are currently in follow-up with no reoccurring leukocytosis. This case series, followed by a short review, provides a long-term clinical and genetic overview of five CNL cases associated with MG.

Commentary: Case report: Chronic neutrophilic leukemia associated with monoclonal gammopathies. A case series and review of genetic characteristics and practical management

“…Further, patients with MGUS with neutrophilia had significantly longer survival than those with isolated CNL. Vermeersch et al (4) found that median survival duration after diagnosis of CNL was 8 years, which may be attributable to some misdiagnoses of CNL; however, median survival of patients in our summary was 22 months, similar to the median survival duration of patients with isolated CNL.…”

“…As a rare subtype of MPN, CNL has been reported as associated with PCD in 16 cases to date. In addition, we also found two cases of CNL associated with lymphoma, namely follicular lymphoma and diffuse large B-cell lymphoma ( 4 , 7 ). This phenomenon suggests that CNL may be more inclined to associated with PCD instead of coexisting by chance.…”

“…Vermeersch et al. published a case series of 5 cases of CNL associated with PCD (CNL-PCD) ( 4 ), however, 3 cases did not appear to meet the 2016 WHO diagnostic criteria for CNL. We identified 16 cases of CNL associated with PCD (including cases 3 and 4 reported by Vermeersch) that meet the latest WHO diagnostic criteria by searching the PubMed and CNKI databases ( Supplementary Material ).…”

When monoclonal gammopathy‐associated chronic neutrophilic leukemia is a reactive process distinct from a clonal myeloproliferative neoplasm: Lessons from mistakes

“…Finally, this report describes a correlated response to BD between PB neutrophils, spleen size, monoclonal component, and serum G‐CSF level. [11, 12] These results suggest that PC‐targeted therapy is efficient in such case and may limit the risk of clonal evolution into a myeloid malignancy by decreasing G‐CSF production.…”

“…BM aspirate revealed a graft-donor myelodysplastic syndrome (MDS) with excess of blast (12%), male karyotype with monosomy 7 associated with TET2 Q1545* (VAF 46%) and ETV6 R418K (VAF 45%) Finally, this report describes a correlated response to BD between PB neutrophils, spleen size, monoclonal component, and serum G-CSF level. [11,12] These results suggest that PC-targeted therapy is efficient in such case and may limit the risk of clonal evolution into a myeloid malignancy by decreasing G-CSF production.…”