Chronic Neutrophilic Leukemia: A Comprehensive Review of Clinical Characteristics, Genetic Landscape and Management

Abstract

Chronic neutrophilic leukemia (CNL) represents a rare disease, that has been classified among the BCR/ABL-negative myeloproliferative neoplasms. The disease is characterized by marked leukocytosis with absolute neutrophilia and its clinical presentation may vary from asymptomatic to highly symptomatic with massive splenomegaly and constitutional symptoms. CNL prognosis remains relatively poor, as most patients succumb to disease complications or transform to acute myeloid leukemia. Recent studies have demonstrated that CSF3R mutations drive the disease, albeit the presence of other secondary mutations perplex the genetic landscape of the disease. Notably, the presence of CSF3R mutations has been adopted as a criterion for diagnosis of CNL. Despite the vigorous research, the management of the disease remains suboptimal. Allogeneic stem cell transplantation represents the only treatment that could lead to cure; however, it is accompanied by high rates of treatment-related mortality. Recently, ruxolitinib has shown significant responses in patients with CNL; however, emergence of resistance might perturbate long-term management of the disease. The aim of this review is to summarize the clinical course and laboratory findings of CNL, highlight its pathogenesis and complex genetic landscape, and provide the context for the appropriate management of patients with CNL.

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

“…The prognosis of patients with CNL is poor, with a median survival of approximately 24 months ( 1 ). Pardanani et al.…”

“…Most patients with CNL have no obvious symptoms and often seek medical attention due to elevated peripheral blood white blood cells detected during physical examinations. Patients often go through an asymptomatic or mild stage, characterized by elevated neutrophils, with or without splenomegaly, which can last for several months to years, and may be misdiagnosed as infection or tumor causing secondary neutrophilia ( 1 ). Due to limitations in understanding of early-stage CNL, most previously reported cases of CNL associated with plasma cell disease (PCD) had reactive neutrophilia, which is a leukemia-like reaction caused by PCD.…”

CSF3R T618I mutant myelodysplastic/myeloproliferative neoplasm in the elderly: An age-related disease with unfavorable prognosis

“…There has been a vigorous debate whether CNL was truly a MPN or should be classified as MDS/MPN as it might share some clinical, hematological and cytogenetic features with MDS or MDS/MPN [16] . In the literature, there were rare reported CNL cases with evidence of significant dysplasia.…”

Myelodysplastic Syndromes/Myeloproliferative Overlap Neoplasms and Differential Diagnosis in the WHO and ICC 2022 Era: A Focused Review

“…The higher frequency of CSF3R mutations in CNL [ 51 ] has been proposed as an additional criterion to orient the diagnosis; however, CSF3R mutations can be seen also in MDS/MPN with neutrophilia with highly variable frequency in different studies [ 52 , 53 , 54 , 55 ]. Therefore the real impact of CSF3R variants for the differential diagnosis of the two disorders is currently a matter of debate [ 56 ].…”