Paroxysmal nocturnal hemoglobinuria (PNH) clones may predict treatment response and support clinical follow-up timing for patients with myelodysplastic syndromes (MDS) and aplastic anemia (AA), according to research published in Leukemia.

PNH clones are more present in patients with bone marrow failure syndromes. In a single center study, researchers tested 869 patients with MDS and 531 patients with AA by high-sensitive cytometry to determine the prevalence of PNH clones. Researchers used flow cytometry with fluorescent aerolysin (FLAER)-based assay.

The authors correlated the PNH clone size with lab features, treatment response and outcomes. In this study, the authors defined small clones as those <10%, and included very small clones at <1%, which many labs do not count as positive.

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Of the patients with MDS, 20.3% had PNH clones present. PNH-positive patients were more often treated with immunosuppressive therapy than chemotherapy. PNH-positive patients had higher response rates to immunosuppressive therapy (84% vs 44.7%, P =.01) and hematopoietic stem cell transplantation (HSCT; 71% vs 56.6%, P =.09) than PNH-negative patients.

In a subanalysis, about 15% of patients with MDS with excess of blasts (EB1/2) were PNH positive. PNH-positive patients experienced the same overall survival and treatment response benefits as those seen in the larger MDS cohort.

Patients with MDS with PNH clones were at greater risk of thrombotic events, and recent research finds this risk even in non-hemolytic patients.

Of the patients with AA, 61.6% had a PNH clone. PNH-positive patients with AA also responded better to immunosuppressive therapy (78% vs 50%, P <.0001) and to HSCT (97% vs 77%, P =.01) than PNH-negative patients with AA.

PNH-positive patients with MDS and AA less frequently evolved to acute myeloid leukemia (AML) than PNH-negative patients. PNH-negative patients also had worse overall survival at 8 years than PNH-positive (51% vs 73%, P <.0001). Patients with larger clone size also saw a decrease in cumulative incidence of death. Patients with AA were more likely to have larger clones.

Overall PNH positivity of any clone size was predictive of good response to immunosuppressive therapy and HSCT for both AA and MDS. Even small PNH clone sizes had a positive impact on overall survival and reduced cumulative incidence of death. Younger patients who were PNH-positive had favorable outcomes after HSCT.

The study included low-risk and high-risk MDS patients, and PNH-positivity retained its predictive value across all risk groups. The authors concluded that PNH clones have a positive predictive and prognostic value in patients with MDS and AA.

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


Fattizzo B, Ireland R, Dunlop A, et al. Clinical and prognostic significance of small paroxysmal nocturnal hemoglobinuria clones in myelodysplastic syndrome and aplastic anemia. Leukemia. Published online March 4, 2021. doi:10.1038/s41375-021-01190-9