Predictors and kinetics of ATO-induced leukocytosis in acute promyelocytic leukemia patients: a retrospective study

BACKGROUND: Although Arsenic trioxide (ATO) has revolutionized acute promyelocytic leukaemia (APL) from a uniformly fatal disease to one of the most curable leukemias, leukocytosis is a common life-threatening side effect and is associated with inferior results. This study aimed to describe leukocyte proliferation kinetics and explore predictors of leukocytosis among APL patients in order to guide individualized application of ATO. RESULTS: In this retrospective study of 100 patients, the incidence of leukocytosis in the single drug ATO group was 74.5%, while that in the ATO- chemotherapy group was 93.9% (P = 0.018). The dynamic changes in leukocytosis showed a higher WBC count in the ATO-chemotherapy group. The median time to leukocytosis was the 9th day (IQR, 6.00-14.00). The duration of leukocytosis was shorter in the ATO single agent group. The uni-variate analysis and multi-variable analysis showed that the same independent prognostic factor was the time to double WBC for leukocytosis for all patients (OR 11.459, 95% CI, 2.121-61.897) and ATO single agent patients (OR 16.603, 95% CI, 1.635-168.635). The area under the ROC curve was 0.835 (95% CI, 0.700-0.971) for all APL patients and 0.822 (95% CI, 0.675-0.969) for single ATO-induced leukocytosis. CONCLUSIONS: The kinetics of leukocytosis induced by single-agent ATO and ATO-chemotherapy were different. The time to double WBC≤7th day was identified as an independent poor prognostic factor for single ATO-induced leukocytosis in APL patients.