Between January 2015 and December 2020, a total of 92 newly diagnosed patients were admitted to our hematology department. Of these, 60 patients were categorized into the low-intermediate risk group, and the remaining patients were categorized into the high risk group, based on Sanz's risk stratification model for survival prediction (9). All 58 patients (34 males and 24 females), with a median age of 34 years (range 17-71 years)] with low-intermediate risk, who had complete clinical data, were retrospectively enrolled in this study. Disease diagnosis was confirmed by bone marrow aspiration, chromosome karyotyping analysis, fluorescence in situ hybridization analysis and polymerase chain reaction. Informed consent prior to and regarding the treatment protocol was obtained from all patients analyzed in the present study.

When a diagnosis of APL was suspected, ATRA (20 mg/m²/day) was administered at the earliest, until complete remission (CR) was achieved. All 58 patients received ATRA and ATO-based induction treatment. If the WBC count increased, cytotoxic agents-based chemotherapy was initiated based on the clinician's decision in order to reduce leukemia cells and prevent risks of DS. A total of 19 cases received idarubicin (8 mg/m²/day on days 1-3), 32 cases received daunorubicin (45 mg/m²/day on days 1-3), two cases received daunorubicin (45 mg/m²/day on days 1-3) combined with cytarabine (100 mg/m²/day on days 1-7), and five cases received only hydroxyurea (2.0-3.0 g/day, adjusted according to blood cells). Blood product support was applied to maintain platelet (PLT) level ≥30x10⁹/l, hemoglobin level ≥70 g/l and plasma fibrinogen level ≥1.5 g/l. All adverse events related to treatments, including bone marrow depression, infection and bleeding, were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03(10).

DS was diagnosed based on the incidence of at least two of the following clinical features: Unexplained fever, acute respiratory distress with interstitial pulmonary infiltrates, acute renal failure, weight gain >5 kg, unexplained hypotension, and pleuropericardial effusion (11). Prevention strategies included dexamethasone (10 mg q12h), and discontinuation of ATRA and ATO. All 58 patients were categorized according to Sanz's risk stratification score (9) as low risk (WBC count <10.0x10⁹/l and PLT ≥40.0x10⁹/l at diagnosis) and intermediate risk (WBC count <10x10⁹/l and PLT <40.0x10⁹/l). CR was defined as the presence of <5% blast cells in bone marrow aspirates, PLT >100x10⁹/l and no juvenile cells in peripheral blood according to the criteria established by the US National Cancer Institute (12). Early mortality was defined as fatality during induction treatment from the first day of hospitalization. Eastern Cooperative Oncology Group (ECOG) performance status score (0-4 score) was applied to investigate the patient's physical status prior to chemotherapy (13). WBC count >4x10⁹/l and WBC multiplication time <3 days was defined as rapid WBC multiplication. Table I presents a comparison of the baseline clinical and laboratory parameters of the groups with rapid WBC multiplication and without rapid WBC multiplication.

Statistical analysis was performed with SPSS v.22.0 software (SPSS Inc.). All data were collected in December 2020. Clinical features are presented as percentages (%) for categorical variables, and as mean values ± standard deviation for normally distributed continuous variables. The χ² test was used to analyze the significance of differences in the distribution of categorical variables between the patient subsets, and the SNK method and Bonferroni's correction were used to compare the two groups. The unpaired Student's t-test or Mann-Whitney U test was used to analyze the significance of differences in the distributions of continuous parametric variables and ranked variables. Multivariate analysis was performed using a binary logistic regression model. WBC count at diagnosis, WBC count at chemotherapy initiation, peak WBC count, and with or without rapid WBC multiplication were considered in the multivariate analysis to evaluate their effects on DS, early mortality and grade 3-4 bleeding. P<0.05 was considered to indicate statistical significance.

Comparison of the baseline features, clinical and laboratory parameters is shown in Table I. No significant differences were found in age, gender and ECOG score between the two groups. WBC count at diagnosis was slightly higher in the group with rapid WBC multiplication (2.14±1.66 x10⁹/l vs. 3.82±2.98 x10⁹/l, P=0.013). There was no difference between the two groups in Sanz's risk stratification (P=0.121). Biochemical tests showed no differences in uric acid, albumin and creatine levels in patients with or without rapid WBC multiplication. Coagulation functions including activated partial thromboplastin, prothrombin time, fibrinogen and D-dimer level were similar in the two groups.

As depicted in Table II, the incidence of DS was higher (48.1 vs. 6.5%, P=0.000), grade 3-4 bleeding was more frequent (34.8 vs. 6.5%, P=0.022), and peak WBC count was higher (30.4±20.0x10⁹/l vs. 8.67±5.4x10⁹/l, P=0.000) in the rapid WBC multiplication group. There were no differences in bone marrow depression, infection, CR rate, time to achieve CR and early mortality rate between the two groups.

To further evaluate the effects of dynamic changes of WBC count during induction treatment on DS, early mortality and bleeding events, a binary logistic regression model was used. The results of multivariate analysis revealed that WBC count at chemotherapy initiation was an independent risk factor for the occurrence of DS [P=0.040, odds ratio (OR)=1.0216, 95% confidence interval (CI)=1.009-1.465]. Peak WBC count and rapid WBC multiplication were significantly related to grade 3-4 bleeding (P=0.019, OR=0.773, 95% CI=0.623-0.959; P=0.002, OR=99.567, 95% CI=5.738-1727.726). However, WBC count at diagnosis, WBC count at chemotherapy initiation, peak WBC count and rapid WBC multiplication were not independent risk factors for early mortality (Table III).