Abstract

Background: Paroxysmal nocturnal hemoglobinuria (PNH) clones are detected in up to 60% of patients with aplastic anemia (AA), yet 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 in 64 patients (30.9%) at diagnosis. Treatment modalities included IST (n = 104) and HSCT (n = 103). Clinical outcomes including overall survival (OS), event-free survival (EFS), graft-versus-host disease (GVHD), relapse, and non-relapse mortality (NRM), were compared between PNH-positive and PNH-negative cohorts.
Results: At 5 years, PNH-positive patients treated with IST had significantly improved OS (100% vs. 72.4%, p = 0.004) compared to PNH-negative patients. In the HSCT group, OS was 100% in PNH-positive versus 90% in PNH-negative patients (p = 0.09). Chronic GVHD incidence post-HSCT was significantly lower in the PNH-positive group (4% vs. 27%, p = 0.01), while acute GVHD, graft failure, and relapse rates were comparable. Clone size (small vs. large) did not impact survival or GVHD outcomes.
Conclusion: The presence of a PNH clone in AA is associated with superior survival following IST and reduced 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.