2.2. Statistical analysis
Significance testing for comparisons in categorical variables was performed using the Chi-square test or Chi-square with Yates’ correction, while the Mann-Whitney U test was utilized for continuous variables. Multinomial logistic regression was employed to calculate odds ratios of impact factors for the occurrence of EMI at different time points. Event free survival (EFS) and overall survival (OS) were analyzed by Kaplan-Meier method and the comparison of survival distributions was conducted using the log-rank test. Cox-proportional hazard models were employed for multivariate analysis of prognostic markers. Statistical significance was defined as P value less than 0.05.
Results
In this cohort, a total of 713 patients were included, with 628 originating from AAML0531, 85 from AAML03P1. The median follow-up period was 2035 days. Among these patients, 123 (17.3%) were diagnosed with EMI at initial diagnosis. 255 (35.8%) patients experienced relapse, out of which, 64 (25.2%) were present with extramedullary infiltration at relapse.
Clinical characteristics of pediatric AML patients with EMI at initial diagnosis
The clinical characteristics of patients with EMI at initial diagnosis are presented in Table 1. Among the 123 patients who had EMI at the time of initial diagnosis (EMI positive group), 36 exclusively presented with CNS involvement only, 75 were diagnosed with myeloid sarcoma, and 12 displayed concurrent CNS involvement and MS. Out of these patients, 24 (19.5%) exhibited hyperleukocytosis (WBC ≥100×109/L), and the median WBC count, BM blast percentage, and PB blast percentage were 27.0×109/L, 70.0%, and 41.0%, respectively, which were not significantly different from those without EMI at diagnosis (EMI negative group) (p>0.05). In the EMI positive group, 30.9% (38/123) of patients were ≤2 years old, which was a significantly higher proportion than that in the EMI negative group (30.9% vs. 15.3%, p <0.0001). According to the FAB classification, only 6.5% (8/123) of EMI positive group patients were classified as M1, which was significantly lower than the corresponding percentage in the EMI negative group patients (6.5% vs. 13.9%, p=0.0247). Moreover, the EMI positive group had a higher frequency of M5 morphology (32.5% vs. 19.7%, p=0.0017). In the analysis of molecular genetics, only 1 patient (0.8%) in the EMI positve group had FLT3 ITD-/NPM1+ , which was significantly lower than that in the EMI negative group (0.8% vs. 5.9%, p=0.0183). There were no significant differences in the occurrence of CEBPA , WT1 and C-KIT gene mutations between the two groups (p > 0.05). Additionally, we found that the EMI positive group exhibited higher frequencies ofKMT2A gene rearrangements than the EMI negative group (27.6% vs. 16.3%, p=0.0030). In cytogenetic analysis, there were no statistically significant differences in the prevalence of complex karyotypes, t(8:21), inv(16), del5q/del7q/-5/-7, trisomy 8/trisomy 21, and minus X/minus Y between the two groups. However, we observed that the proportion of normal karyotype in the EMI positive group was significantly lower than that in the EMI negative group (12.2% vs. 26.6%, p=0.0007).
Table 1. The clinical characteristics of de novo pediatric AML patients with and without EMI at initial diagnosis, and relapse patients with and without EMI involvement.