Serial Analysis of Clonal Expansion in PNH by Flow Cytometry

Abstract

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disorder caused by PIG-A mutations. To assess clonal expansion in PNH over time, patients with serial testing by flow cytometry (interval of at least one year) were analyzed. This study involved 164 patients with PNH from Duke (DP) and 151 patients from Japan (JP). The mean fraction of PMNs deficient in CD59 (mean±SE) was 75.2±4.2% in DP and 40.0 + 8.3% (n=21) in JP at the initial analysis, and were 74.1 ±4.7% and 50.7 + 8.6% at the latest analysis (P=NS). However, in individual cases, the proportion of affected PMNs varied considerably from -84% to +98%. Some DP and JP pts, however, had a diminution in their CD59-deficient PMNs over time, which was associated with the development of overall hematopoietic failure (P=.04 for DP, P=.05 for JP). These data illustrate the complexity of clonal expansion in PNH, and the marked variability over time. GPI-deficient populations vary considerably over time for individual patients, but a decreasing PNH clone indicates impending hematopoietic failure. Correlation between clonal expansion or diminution and the development or recovery from aplasia will help our understanding of the natural history of PNH.