Clonal Dynamics of GPI-Deficient Cells in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH): A Retrospective Follow-Up Analysis.

This retrospective, single-center study aimed to characterize clonal dynamics of GPI-deficient cells in patients with paroxysmal nocturnal hemoglobinuria (PNH) or PNH/aplastic anemia (AA) syndrome using multiparameter flow cytometry including FLAER. Among 108 patients diagnosed and treated at our center, 83 had longitudinal monitoring of GPI-deficient neutrophils; 53 of these also had data on monocytes and lymphocytes. Median observation time was 29.4 months (range 1.1-162.7 months). Clone size in neutrophils showed a strong correlation with monocytes, but not with lymphocytes. Clonal persistence represented the most frequent individual pattern of clone evolution observed during follow-up; clonal persistence was observed in 32/83 patients, while 24 patients exhibited clonal expansion (≥ 10%) and 13 showed regression. Expansion frequently involved all three lineages, suggesting ongoing biological mechanisms contributing to clonal selection. Regression was more likely in patients with small initial clones. In six patients undergoing allogeneic stem cell transplantation, complete eradication of PNH clones was achieved. Clonal dynamics were independent of eculizumab treatment; however, regression was observed in some patients treated with ATG and cyclosporine A. These findings support the need for longitudinal clone size monitoring, particularly in neutrophils and monocytes. Further studies are warranted to elucidate factors influencing clone expansion and remission. Trial Registration: 25-12 634-BO.