Analysis of risk factors for differentiation syndrome in patients with acute promyelocytic leukemia

Differentiation syndrome (DS) is a potentially life-threatening complication during induction therapy for acute promyelocytic leukemia (APL). Despite therapeutic advances, early identification of patients at high risk for DS remains clinically critical. This study aimed to investigate clinical, laboratory, and treatment-related risk factors associated with DS in patients with newly diagnosed APL. This retrospective observational study included 316 adult patients diagnosed with APL between January 2014 and December 2024. Diagnosis was confirmed by cytomorphology, immunophenotyping, cytogenetics, and detection of the PML-RARA fusion gene. All patients received induction therapy with all-trans retinoic acid, arsenic trioxide, or both. Clinical and laboratory parameters were compared between DS (n = 96) and non-DS (n = 220) groups. Logistic regression analysis was used to identify independent predictors of DS. The incidence of DS was 30.4%. Compared to the non-DS group, DS patients exhibited significantly higher white blood cell (WBC) counts, neutrophil counts, and percentages of bone marrow and peripheral blood blasts (all P < .001). Coagulation abnormalities (prolonged prothrombin time, reduced fibrinogen) and hypoalbuminemia were more frequent in the DS group. Multivariate analysis identified 3 independent risk factors: absence of prophylactic corticosteroid use (odds ratio [OR] 0.10, 95% confidence interval [CI] 0.03-0.35), elevated peak WBC during induction (OR 1.07, 95% CI 1.03-1.11), and lower baseline serum albumin (OR 0.86, 95% CI 0.79-0.93). Elevated peak WBC, hypoalbuminemia, and lack of prophylactic corticosteroids are independent predictors of DS in APL patients. These findings underscore the importance of early risk stratification and preventive strategies to mitigate DS risk during induction therapy.