Is chronic neutropenia always a benign disease? Evidences from a 5-year prospective study

To evaluate infections and oncohematologic evolution in adult patients with chronic idiopathic and autoimmune neutropenia in a prospective study.

76 consecutive patients were enrolled from September 2008 to April 2012. Complete blood counts and clinical evaluation were performed at enrolment, at month 3, 6, and then every 6 months. Anti-neutrophil antibodies were tested by GIFT method.

Patients (49 chronic idiopathic- and 27 autoimmune neutropenia) were followed for a median of 5 years (range 24-84 months). At enrolment, neutropenia was mild in 44 patients (median neutrophils 1.27×10(3)/μL), moderate in 23 (median 0.8×10(3)/μL), and severe in 9 (median 0.4×10(3)/μL). Neutrophil counts showed a great inter-subject but no intra-subject variability, with lower values in autoimmune neutropenia, in males, and in MGUS cases. Over time, no grade >3 infections occurred; 13/49 chronic idiopathic and 6/27 autoimmune neutropenia patients experienced a grade 2 event, irrespective of mean and nadir neutrophil values. Bone marrow evaluation at enrolment showed reduced cellularity in 23% of cases, and dyserythropoietic features in 55%, with no definite hematologic diagnosis. During the follow-up, 5 cases were diagnosed with NK expansion, 4 with hairy cell leukemia, and 3 with myelodysplasia (1 myelomonocytic leukemia, 1 refractory cytopenia with unilineage dysplasia, and 1 multilineage dysplasia), with a median time to evolution of 30 months.

Chronic idiopathic and autoimmune neutropenia, although usually benign, deserve hematological follow-up with a bone marrow evaluation at diagnosis and a re-evaluation in the presence of worsening neutropenia, appearance of additional cytopenias, and lymphocytosis.