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Objective: To explore the clinical characteristics and prognosis of acute erythroid leukemia (AEL). Methods: A retrospective case series study was conducted. Clinical data from 23 patients with AEL admitted to the Department of Hematology at the First Affiliated Hospital of Nanjing Medical University from January 2015 to May 2025 were collected. Laboratory features and prognostic outcomes were summarized. Overall survival (OS) was analyzed using the Kaplan-Meier method, and log-rank test was used for comparisons between groups. Results: Among the 23 patients with AEL, 13 were male (56.5%) and 10 were female (43.5%), with a median age of 62 years (range: 13-80 years). Of these patients, 10 (43.5%) had primary AEL, 5 (21.7%) had treatment-related AEL, and 8 (34.8%) had AEL secondary to other myeloid diseases. Among the secondary AEL cases, 5 were associated with myelodysplastic syndrome, 2 with chronic myeloid leukemia, and 1 with aplastic anemia. Regarding TP53 abnormalities, 38.1% (8/21) of patients had TP53 deletions, and among the 16 patients who underwent next-generation sequencing, all had TP53 mutations. The most frequent TP53 mutation sites were R248Q/W/L/P (3/16), H193R/D/L (2/16), and C242 frameshift mutations (2/16). The median OS was 1.23 months (range: 0.27-13.53 months). The median OS was 1.00 month (95%CI 0.77-1.23) in patients with TP53 mutation frequency >40% (n=8), compared with 3.07 months (95%CI 0-6.81) in those with TP53 mutation frequency ≤40% (n=8). The difference in OS between the two groups was statistically significant (χ²=7.65, P=0.006). There was no statistically significant difference in OS between patients receiving intensive chemotherapy and those receiving low-intensity chemotherapy (P=0.161). The median OS was 2.20 months (95%CI 1.06-3.34) in the primary group, 7.20 months (95%CI 0-20.01) in the treatment-related group, and 0.93 months (95%CI 0.66-1.21) in the secondary group. Survival differed significantly among the three etiological groups (χ²=11.53, P=0.003). Conclusion: AEL is a subtype of acute myeloid leukemia with extremely poor prognosis that is highly associated with TP53 gene abnormalities.