Chronic neutrophilic leukemia (CNL): a clinical, pathologic and cytogenetic study

Abstract

This report describes a single institution's recent experience with six patients fulfilling the diagnostic criteria of chronic neutrophilic leukemia. No patient had the Philadelphia chromosome or the BCR/ABL fusion gene. None of the common cytogenetic abnormalities characteristic of myeloid disorders were detected. Two patients demonstrated clonal evolution during the course of the disease. All responded initially to therapy with hydroxyurea with control of leukocytosis and reduction in splenomegaly. Three patients eventually became refractory to hydroxyurea, manifesting progressive neutrophilia without blastic transformation. Aggressive chemotherapy to control progressive leukocytosis resulted in death due to cytopenias in two of these patients. The third patient received less intensive chemotherapy and died of progressive disease. One patient died after transformation of the disease into undifferentiated acute myeloid leukemia. Two patients remain alive with stable disease on hydroxyurea therapy, 12 and 54 months after initial diagnosis. Chronic neutrophilic leukemia is a rare clinicopathologic entity that can be distinguished from chronic myelogenous leukemia, the recently described neutrophilic-chronic myelogenous leukemia, and myelodysplastic syndrome. The clinical course is heterogeneous, with a definite risk of death from either blastic transformation or progressive neutrophilic leukocytosis. Continued study and reporting of these cases must be encouraged. Leukemia (2001) 15, 35-40.

Chronic neutrophilic leukemia 2016: Update on diagnosis, molecular genetics, prognosis, and management

“…As compared with other MPNs, neither megakaryocytic hyperplasia nor clusters of large atypical megakaryocytes are seen. Reticulin fibrosis is uncommon, but reticulin stain may show 11 reticulin fibrosis (on a scale of 0-4) [3,43]. In our series of CF3R-mutated CNL, the BM was hypercellular in all patients with a median of 95% cellularity (range 80-100%) and granulocytic precursors were markedly increased with left-shifted or normal maturation.…”

“…At that time, only 150 cases had been reported in the literature [29,31,32]. A critical review of the literature applying the then recently developed WHO diagnostic criteria, could only confirm this diagnosis in 40 cases, indicating the true rate of occurrence of what is now considered CNL was even lower [5,[32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47]. In this data set of WHO-defined CNL, the median age at diagnosis was 66 years (range: 15 -86) and 56% were males [5].…”

WHO-defined chronic neutrophilic leukemia: a long-term analysis of 12 cases and a critical review of the literature

“…Thus far, subsequent cases of CNL examined have failed to confirm a cryptic p230 as the causative molecular event in CNL. 3,9 Furthermore, all cases of CML with this e19/a2 junction thus far reported have had cytogenetic evidence of the Ph chromosome and many had a phenotype not consistent with CNL. 10 Like other CMPD, the clinical course of CNL is heterogeneous.…”

“…Previously, we reported six cases of CNL in your Journal in 2001 3 and wish to update our original series by providing longterm follow-up, and reporting six additional cases. Of significance, since our earlier publication, the WHO classification has provided stringent diagnostic criteria, enabling a uniform system to ensure the correct diagnosis of this rare CMPD.…”

Early relapse of JAK2 V617F‐positive chronic neutrophilic leukemia with central nervous system infiltration after unrelated bone marrow transplantation

“…Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative disorder which predominantly affects older adults [1][2][3] and characterized by sustained mature neutrophilic leukocytosis in peripheral blood, neutrophilic granulocyte proliferation in the bone marrow, and the absence of the Philadelphia chromosome. Neutrophilia is usually progressive, and anemia and thrombocytopenia occur successively [1].…”