The following is a summary of “Clinical and Molecular Determinants of Clonal Evolution in Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria,” published in the January 2023 issue of Oncology by Gurnari, et al.

The most dangerous long-term side effects in people with aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH) are secondary myeloid neoplasms (sMNs). However, sMNs lacked specialized surveillance methods, early treatment interventions, and precise predictions.

To determine the clinical and genetic factors that influence clonal development, researchers examined a multicenter, retrospective cohort of 1,008 patients with AA and PNH (median follow-up 8.6 years).

The 10-year cumulative incidence of sMN in non-transplanted instances was 11.6%, despite the fact that none of the patients who had upfront transplants (n = 117) experienced clonal problems (either sMN or secondary PNH). Untreated patients exhibited the highest risk among non-severe cases of AA, although higher age at presentation and poor response to immunosuppressive medication were independently related to increased risk of sMN. From AA to sMN, 4.5 years had passed. In 94 cases, sMN manifested. When sMN first manifested, bone marrow blasts were independently linked to a 40% 5-year overall survival rate. The most prevalent features were del7/7q, ASXL1, SETBP1, RUNX1, and RAS pathway gene mutations, together with high-risk phenotypes of myelodysplastic syndrome. It was discovered through cross-sectional analyses of clonal dynamics that myeloid hits gradually replaced PIGA/human leukocyte antigen lesions as time went on. Myeloid-driving lesions were associated with a greater probability of sMN development than PIGA and BCOR/L1 mutant carriers.

The age of patients, illness severity, and lack of response to therapy were all factors that increased the incidence of sMN in AA. sMNs had high-risk molecular, karyotypic, and morphological characteristics. Medical care should be cautious when taking into account the complicated and poorly understood landscape of acquired somatic mutations.

Reference: ascopubs.org/doi/full/10.1200/JCO.22.00710