Cyclic neutropenia: amplification of granulocyte oscillations by lithium and long-term suppression of cycling by plasmapheresis

A patient with well documented cyclic neutropenia (CN) was given chronic lithium therapy as well as a short course of plasmapheresis with therapeutic intention. While on lithium therapy, an increase in the amplitude of the granulocyte oscillations was observed, but recurrent agranulocytotic periods persisted. A 2-wk course of plasmapheresis (total exchange 17 liters) resulted in a gradual decrease of granulocyte oscillations, with the granulocyte count remaining above 500/cu mm at all times, and the patient became asymptomatic. The improvements in the clinical state of the patient have now persisted for more than 9 mo. Quantitative analysis of the oscillation period and the phase lags between peak counts of the hematologic cell lines revealed a 20-day cycle for granulocytes, monocytes, reticulocytes, and platelets, but not for lymphocytes. The observed phase lags, together with the literature values for the intramarrow maturation times of the hematologic cell lines, suggest that the feedback regulation abnormality, believed to be at the basis of CN, primarily affects the stem cell that is still capable of differentiating into granulocytes and monocytes, but that the oscillations of reticulocytes and platelets are the result of a stem cell competition for uncommitted precursor cells by the primarily oscillating granulocyte and monocyte production.