Neutropenia dynamics in a case of T-LGL lymphoproliferation illustrate rapid turnover of granulocyte progenitors

Abstract

Objectives: To elucidate the natural history of T-cell large granular lymphocyte (T-LGL) lymphoproliferation, we followed changes in associated fluctuating neutropenia for 3 years in an untreated patient presenting with the disease.

Materials and methods: We report a nonlinear mathematical analysis of irregular neutrophil fluctuation, using iterative data maps, to detect long-term regulation of the neutrophil population.

Results: This geometric analysis indicated that variations of this sequence of neutrophil counts followed bounded deterministic dynamics around a fixed low level equilibrium, a situation similar to that previously observed for cultured mouse early bone marrow progenitor cells.

Conclusion: These findings illustrate how the deleterious effect of T-LGL on neutrophils is balanced, over periods of years, by pulses of compensatory neutrophil production, potentially accounting for the commonly observed prolonged indolent course of the disease.

Figure 1

White blood cell counts/mm ³ . Lymphocytes, open circles; neutrophils, dark squares. X‐axis in time (days), Y‐axis cell counts/mm³ (Local steroid treatment: arrow).

Figure 2

Trend analysis. Lymphocytes, red diamonds; neutrophils, black squares. X‐axis: moving average (MA) for time (days); Y‐axis: MA for cell counts/mm³.

Figure 3

Topological representation of neutrophil counts. X‐axis, cell count/mm³ (x _i); Y‐axis, the cell count/mm³ (x _i+1). (a) Bisecting lines (dotted) of vectors representing peaks of neutrophil counts, oriented downwards, meeting at coordinates 1203/1203 (n=5) and 913/913 (n=4). (b) Five lines (dotted), bisecting troughs oriented upwards, meeting at coordinates ∼1150/1150. Vector following steroid treatment is between points 12 and 13 (arrow).