Paroxysmal Nocturnal Hemoglobinuria with Large Clones in Non-Hypoplastic Myelodysplastic Syndrome: Report of Two...

Paroxysmal nocturnal hemoglobinuria (PNH) clones are frequently found in hypoplastic myelodysplastic syndromes (hMDS), though less commonly than in aplastic anemia. In contrast, the coexistence of hemolytic PNH with large clones and classical, hypercellular MDS (non-hMDS) is rare and likely underrecognized in clinical practice. Since 2014, 229 MDS patients have been seen at our department. Here, we report two cases with this association and discuss their particular diagnostic and treatment challenges.

The first case is a 68-year-old woman with a hemolytic PNH of 59 years duration. We first saw her in June 2021; she had pancytopenia, with values stable over the past 25 years. After a complete work-up, MDS with low blasts and SF3B1 mutation was diagnosed. She was subsequently diagnosed with symptomatic pulmonary hypertension, and in 2023, she started therapy with ravulizumab, achieving good disease control. The second case concerns a 76-year-old man diagnosed with MDS at age 74. One year later, his anemia worsened, and hemolytic PNH with large clones was diagnosed. The patient showed initial benefit from ravulizumab, and he was later switched to pegcetacoplan, which led to effective disease control.

We want to emphasize the importance of assessing PNH clones in the diagnosis of non-hMDS, especially in cases with significant anemia. Regarding PNH treatment in such patients, we found that they are underrepresented in studies investigating complement inhibitor. However, standard doses recommended for PNH appear effective and safe regardless of the underlying disease.