Chronic benign neutropenia in adults: clinical features in a 4-year prospective study

Chronic benign neutropenia (CBN) is a rare acquired hematological condition, defined by an absolute neutrophil count (ANCs) lower than 1800/µl in white and 1500/µl in black people for more than 3 months, in the absence of any underlying disease; CBN may be idiopathic or autoimmune based on the absence/presence of anti-neutrophils antibodies. In this prospective study we followed up 52 patients with CBN (19 males and 33 females, median age 55 years, range 25-86 years) for a median time of 48 months from January 2009, focusing on 1) ANCs variations (by general estimating equations GEE models), 2) positivity for anti-neutrophil antibodies (by direct and indirect granulocyte immunofluorescence test), 3) bone marrow features, and 4) incidence of infectious episodes. As shown in Figure 1, the mean ANCs were stably under the normal range (1500-6500/µl) at all the time points considered; by GEE analysis, a great inter-subject variability was observed during the follow-up (p=0.012), whereas no significant intra-subject variations were found. The mean ANCs observed during the follow up were significantly lower in males than in females (p=0.023) and in cases with mild splenomegaly, although not significantly (10 cases, 20%, mean maximal diameter 11,4 cm by ultrasonography), independently from gender (multivariate analysis). Anti-neutrophil antibodies were detected in 19/52 patients (37%), and mean ANCs values over the follow up were significantly lower in positive versus negative cases (p=0.027). Bone marrow evaluation (N=27) showed features of dismyelopoiesis in 15 cases (56%), hypocellularity in 3 (11%) and normal morphology in 9 (33%), and flow cytometry demonstrated increased Natural Killer cells in 13 patients (25%). Finally, 9 patients (17%) showed monocytosis, and 5 (10%) a MGUS. An infection needing oral antibiotic or antiviral therapy occurred in 13 patients (25%) (2 pneumonias, 7 upper respiratory tract, 3 Herpes Zoster Virus and 1 urinary tract infections), without relationship with the patient’s mean ANCs value, the nadir of ANC value, nor with the presence of anti-neutrophil antibodies. In conclusion, CBN in adults is a benign disease, with an infectious rate not superior to that of the general population and a great variability in ANCs values. Bone marrow evaluation shows abnormal findings in half of patients, without reaching the criteria for clonal hematological diseases, but suggesting that this condition deserves clinical follow up.