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.