Neutrophil kinetics in chronic neutropenia

Abstract

Quantitative studies of bone marrow neutrophil pool sizes and production rates and of blood neutrophil kinetics were performed in 16 patients with chronic neutropenia without splenomegaly. Marrow netrophil cellularity was determined from a ferrokinetic estimate of marrow normoblasts and from neutrophil-erythroid ratios determined from marrow sections. Postmitotic pool turnover was derived from the postmitotic pool size and transit time, the latter determined from 3H-thymidine neutrophil emergence time. Blood neutrophil kinetics were studied with 32P-diisopropylfluoophosphate-labeled autologous neutrophils. Mitotic pool size was basal or below basal in 12 of the 16 patients. The turnover of the post-mitotic neutrophils was subbasal in 6, basal in 7, and above basal in 3 patients. Blood neutrophil turnover was within the normal range in 8 patients and decreased in 8. The degree of ineffective granulocytopoiesis was assessed by comparing the relative size of the mitotic pool, postmitotic pool turnover, and blood turnover. On this basis, 13 of the 16 patients showed appreciable degrees of ineffective granulocytopoiesis. Ineffective neutrophil production occurred both early and late in neutrophil development. These studies indicate that most patients with chronic neutropenia without splenomegaly lack a proliferative marrow response to the neutropenia and suggest that ineffective granulocytopoiesis is a common feature of this disorder.