Detection of PNH clones can aid in the distinction of aplastic anemia vs inherited BM failure syndromes: a single center experience and review of the literature.

Acquired aplastic anemia (AA) and inherited bone marrow (BM) failure syndromes (IBMFSs) are both life-threatening diseases characterized by BM failure, and cytopenia-related complications. Distinction between AA and IBMFS is essential as it has implications for optimal treatment and transplant decisions. However, this often requires syndrome-specific functional and genetic testing, which can delay initiation of treatment. The detection of a paroxysmal nocturnal hemoglobinuria (PNH) clone has been suggested to be helpful in ruling out IBMFS, but limited data exists. In this analysis, 144 patients with either a diagnosis of AA (n=79) or IBMFS (n=65) established in the last four years were assessed and 85 had available PNH testing. Among AA patients, 69% were found to possess a PNH clone (minor clones if the percentage was 0.01 to 1%, small clones from 1 to 10%, and major clones above 10%), while only 5% of IBMFS patients had a PNH clone detected (p<0.0001) and no patient with an IBFMS had a PNH clone larger than 0.1%. This highlights that while the absence of a PNH clone does not rule out AA, the identification of a PNH clone is strongly suggestive of AA and can help rule out an IBMFS, allowing a more rapid initiation of treatment and transplant decision-making.