Prognostic significance of PNH clones in aplastic anemia treated with immunosuppression or allogeneic HSCT

Abstract Background: Aplastic anemia (AA) is a type of bone marrow failure caused by immune-mediated destruction of hematopoietic stem cells. Paroxysmal Nocturnal Hemoglobinuria clone (PNH) is often associated with AA (50%–60% of cases). The treatment of AA depends on the disease severity, patient's age and donor availability. In young patients with severe AA, frontline allogenic hematopoietic stem cell transplantation (HSCT) is the standard of care. Method: Retrospective analysis of 207 AA patients diagnosed and received frontline therapy in a single institution between 2004 and 2024. Patient'scharacteristics were summarized using frequencies with percentages for categorical variables and medians with interquartile ranges for continuous variables. Probabilities of OS and EFS were summarized using Kaplan-Meier estimator with variance calculated using Greenwood formula. Result: 109 (52.6%) were males and 98 (47.3%) were females, median age was 23 (IQR 18-31) years. 143 (69.0%) were PNH negative and 64 (30.9%) were PNH positive (41 had a small clone and 23 had a large clone). 104 (50.3%) patients received IST and 103 (49.7%) patients underwent HSCT as frontline therapy. In the IST cohort, the treatment included cyclosporine plus ATG (horse or rabbit) ± Eltombopag for 77 patients (74%) and 27(26%) received other types of IST (Mycophenolate mofetil, danazol, steroid). In the HSCT cohort, 98 patients (95.1%) were transplanted using a MSD, 4 (3.8%) haploidentical related donor and 1(0.9%) MUD. After a median follow up duration of 102 (95 CI : 90.6-114.3) months, the overall survival (OS) at 5 yearsfor the IST group, was 100% for PNH-positive compared to 72.4% for PNH-negative (p = 0.004). Among the transplanted cohort, the OS was 100% for PNH-positive and 90% for PNH-negative patients (p = 0.09). In whole population PNH-positive and PNH-negative groups, event-free survival at 5 years was 60% versus 37.6%, respectively, (p = 0.08). Post-HSCT, the cumulative incidence of acute GvHD in PNH-positive and PNH-negative patients was 10% and 15%, respectively, (p = 0.16), while chronic GvHD incidence was 4% and 27%, respectively (p = 0.01). The graft failure rates were 18% in PNH-positive and 10% in PNH-negative patients, (p = 0.5), whereas the relapse rate post IST was 36.3% in PNH-positive and 50% in PNH-negative patients in the IST group (p = 0.2).TheNon relapse mortality (NRM) post-HSCT was 0% in the PNH-positive group versus 10% in the PNH-negative group, (p = 0.08). There was no difference in the incidence of GVHD, GF or relapse between patients with small ( 10%) and large (10%) PNH clones. Conclusion: AA patients with a PNH clone have improved survival with with IST compared to the AA patients without a PNH clone. Post-HSCT both cohorts have good survival, however patients with a PNH clone had lower chronic GVHD incidence. Further studies to delineate the effect of PNH clone on GVHD incidence are needed.