Prognostic significance of PNH clones in aplastic anemia treated with immunosuppression or allogeneic HSCT: a 20-year single-center experience

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) clones are detected in up to 60% of patients with aplastic anemia (AA); however, their prognostic impact remains incompletely defined, particularly in the context of frontline immunosuppressive therapy (IST) or allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: We retrospectively analyzed 207 patients with AA treated between 2004 and 2024 at a single institution. PNH clones were identified at diagnosis in 64 patients (30.9%). Treatment modalities included IST (n = 104) and HSCT (n = 103). Clinical outcomes, including overall survival (OS), event-free survival, graft-versus-host disease (GVHD), relapse, and non-relapse mortality, were compared between the PNH-positive and PNH-negative cohorts. RESULTS: At 5 years, PNH-positive patients treated with IST had significantly improved OS compared with PNH-negative patients (100% vs. 72.4%, p = 0.004). In the HSCT group, OS was 100% in PNH-positive patients versus 90% in PNH-negative patients (p = 0.09). The incidence of chronic GVHD after HSCT was significantly lower in the PNH-positive group (4% vs. 27%, p = 0.01), whereas the rates of acute GVHD, graft failure, and relapse were comparable. Clone size (small vs. large) did not affect survival or GVHD outcomes. CONCLUSIONS: The presence of a PNH clone in AA was associated with superior survival following IST and a lower incidence of chronic GVHD following HSCT. These findings suggest that PNH positivity may serve as a prognostic and immunomodulatory biomarker in AA and support its integration into therapeutic decision-making and risk stratification algorithms.