Evolution patterns of paroxysmal nocturnal hemoglobinuria clone and clinical implications in acquired bone marrow failure

Abstract

The paroxysmal nocturnal hemoglobinuria (PNH) clone often presents in acquired bone marrow failure (aBMF), which is involved in more than half of aplastic anemia (AA) cases and about 10%-20% of myelodysplastic syndrome (MDS) cases. PNH clone expansion patterns and clinical implications, however, remain obscure. We conducted a large retrospective study of 457 aBMF patients with positive PNH clones to explore the wide spectrum of clone architecture, evolution patterns, and clinical implications. PNH clone size at diagnosis in AA or MDS was significantly smaller than that in clinical PNH (p < 0.001); the main clone patterns in AA and MDS were granulocyte dominant, with the remaining cases having a granulocyte-erythrocyte balance pattern in clinical PNH. In 131 AA patients at follow-up, there was no obvious difference in response rates between those with the aggressive pattern of clone evolution (73.7%) and those with the stable pattern (81.1%). A quarter of AA patients evolved into clinical hemolysis within a median interval of 11 months. AA cases progressing into clinical hemolysis after immunosuppressive therapy had significantly larger clones (granulocytes: 12.3% vs. 2.6%; erythrocytes: 5.7% vs. 1.3%) at diagnosis and presented mainly an aggressive pattern, especially the granulocyte-erythrocyte aggressive model. Clone sizes reaching 37% for erythrocytes and 28% for granulocytes were indicators of the onset of hemolysis in AA. In conclusion, aBMF patients presented significantly various PNH clone patterns at diagnosis. AA patients with either an aggressive or stable evolution pattern can achieve a response, but patients with an aggressive evolution pattern, especially the granulocyte-erythrocyte aggressive model, tend to evolve into clinical hemolysis.