Evolving of treatment paradigms and challenges in acute promyelocytic leukaemia: A real-world analysis of 1105 patients over the last three decades.

Although acute promyelocytic leukaemia (APL) is a highly curable disease, challenges of early death (ED) and relapse still exist, and real-world data are scarce in the ATRA plus ATO era. A total of 1105 APL patients from 1990 to 2020 were enrolled and categorized into three treatment periods, namely ATRA, ATRA plus ATO, and risk-adapted therapy. The early death (ED) rate was 20.2%, 10.1%, and 7.0%, respectively, in three periods, while there was no significant decline in the 7-day death rate. Consistently, the overall survival (OS) and disease-free survival (DFS) of APL patients markedly improved over time. Despite the last two periods exhibiting similar DFS, the chemotherapy load was substantially lower in Period 3. Notably, leveraging older age and higher WBC count (especially > 50 × 10/L), we could identify a small group of extremely high-risk patients who had a very high ED rate and poor prognosis, while those with NRAS mutations and higher WBC tended to relapse, both representing obstacles to curing all patients. In conclusion, the evolvement of treatment paradigms can reduce the ED rate, improve clinical outcomes, and spare patients the toxicity of chemotherapy. Special care and innovative agents are warranted for the particularly high-risk APL.