Risk beyond neutropenia: insights into neutrophil migration from newly diagnosed AML until late after allogeneic stem cell transplantation.

Abstract

Quantification of neutrophil counts is the most relevant assessment of cellular immunity in clinical practice. Patients with neutropenia are considered at risk and are categorized according to its severity. The incidence of febrile neutropenia varies, but patients with acute myeloid leukemia are traditionally considered at high risk, especially following myelotoxic treatments. To provide additional functional parameters, we investigated the ex vivo migration properties and morphology of neutrophils in 10 patients with acute myeloid leukemia using single-cell video-microscopy and discovered, in addition to neutropenia, highly pathological neutrophil migration patterns and polarization defects in patients with untreated acute myeloid leukemia. Neutrophil speed was the most sensitive parameter and significantly lower at leukemia diagnosis (9.067 vs 15.810 µm/min, P = 0.0025) compared to healthy controls (n = 46). Hematological remission was associated with improved neutrophil migration profiles, but these ultimately normalized only after hematopoietic cell transplantation. Five patients were followed up for long-term effects of hematopoietic cell transplantation for up to 24 mo. This is the first longitudinal ex vivo neutrophil migration study in patients with acute myeloid leukemia, followed by allogeneic hematopoietic cell transplantation. It identified functional neutrophil impairments beyond routine quantitative assessments, adding to the well-known quantitative impairment of neutropenia. HCT can reestablish functional neutrophils with healthy migration profiles in these patients.