Risk factors associated with early death, disease relapse and second primary malignancies in patients with newly diagnosed acute promyelocytic leukemia

Introduction: Early death (ED), relapse, and second primary malignancies (SPMs) remain major barriers to both early and long-term outcomes in acute promyelocytic leukemia (APL). The prospective identification of key risk factors is essential to mitigate these adverse outcomes. Methods: We retrospectively analyzed 174 consecutive patients with newly diagnosed APL treated at a single center, with a median follow-up of 59 months. We evaluated clinical, laboratory, and treatment-related factors associated with these outcomes, including comparisons across treatment eras and regimen categories, and we summarized institutional practice regarding central nervous system (CNS) prophylaxis and management. Results: Within the cohort, ED occurred in 9 patients, relapse in 7 patients, and SPMs in 7 patients. ED clustered with severe hemorrhagic and thrombotic complications during induction. Relapse was associated with subsequent adverse outcomes, including SPMs and death. Given the low number of events, multivariable modeling was restricted and interpreted cautiously with penalized approaches used as sensitivity analyses where applicable. Discussion: Our findings support the risk-adapted approach emphasizing prompt initiation of ATRA and intensified supportive care in patients with high-risk baseline features, alongside vigilant molecular and long-term surveillance to facilitate early detection and timely management of relapse and SPMs.