Effects of peripheral blood leukocyte count and tumor necrosis factor-alpha on early death in acute promyelocytic leukemia

Background Early death remains a major factor in survival in APL. We aimed to analyze the risk factors for differentiation syndrome and early death in acute promyelocytic leukemia (APL).Methods The clinical data of APL patients who were newly diagnosed at Mianyang Central Hospital from January 2013 to January 2022 were retrospectively analyzed.Results Eighty-six newly diagnosed APL patients (37 males and 49 females) were included in this study. The median age was 46 (17-75) years. Sixty-one patients (70.9%) had low/intermediate-risk APL, and 25 patients (29.1%) had high-risk APL. The incidence of differentiation syndrome (DS) was 62.4%. The multivariate analysis showed that a peak white blood cell (WBC) count > 16 x 10<^>9/L was an independent risk factor (OR = 11.000, 95% CI: 2.830-42.756, P = 0.001) for DS in all APL patients, while a WBC count > 10 x 10<^>9/L on Day 5 was an independent risk factor for DS in low-intermediate risk APL patients (OR = 9.114, 95% CI: 2.384-34.849, P = 0.001). There were 31 patients (36.5%) with mild DS and 22 patients (25.9%) with severe DS. The multivariate analysis showed that WBC count >= 23 x 10<^>9/L at chemotherapy was an independent risk factor for severe DS (OR = 10.500, 95% CI: 2.344-47.034, P = 0.002). The rate of early death (ED) was 24.4% (21/86). The multivariate analysis showed that male gender (OR = 7.578,95% CI:1.136- 50.551, P = 0.036), HGB < 65 g/L (OR = 16.271,95% CI:2.012-131.594, P = 0.009) and WBC count > 7 x 10<^>9/L on Day 3(OR = 23.359,95% CI:1.825-298.959, P = 0.015) were independent risk factors for ED. The WBC count at diagnosis, WBC count on Day 3 and WBC count on Day 5 had moderate positive correlations with tumor necrosis factor-alpha (TNF alpha) at diagnosis, and the correlation coefficients were 0.648 (P = 0.012), 0.615 (P = 0.033), and 0.609 (P = 0.035), respectively. The WBC count had no correlation with IL-6. Conclusion During induction treatment, cytotoxic chemotherapy may need to be initiated to reduce the risk of DS for APL patients with a low-intermediate risk WBC count >= 10 x 10<^>9/L on Day 5 or for all patients with a peak WBC count >= 16 x 10<^>9/L. Patients with WBC > 7 x 10<^>9/L on Day 3 have a higher risk of ED. Leukocyte proliferation is associated with TNF-alpha rather than IL-6, and TNF-alpha may be a potential biomarker for predicting ED.