WBC, white blood cell; BM, bone marrow; PB, peripheral blood; FAB, French-American-British classification; SCT, stem cell transplantation.
a Chi-square with Yates’ correction.
Clinical characteristics of pediatric AML patients with EMI at relapse
255 patients experienced relapse in this cohort, out of which, 64 (25.1%) patients were observed to have EMI at relapse. 37.5% (24/64) of patients initially presented with EMI at diagnosis, all of these patients achieved CR after induction therapy, but later experienced bone marrow relapse or progression of extramedullary disease. A total of 35.9% (23/64) of these patients were ≤2 years at the time of initial diagnosis, which was significantly higher than those without EMI at relapse (35.9% vs. 14.1%, p=0.0001). Furthermore, patients developed EMI at relapse had a higher incidence of hyperleukocytosis at initial diagnosis (35.9% vs. 22.5%, p <0.0338). Similarly, the group of patients with EMI at relapse had a higher proportion of M5 cases (39.1% vs. 21.5%, p=0.0054). In molecular genetics and cytogenetic analysis, there were no differences in the occurrence rates ofCEBPA , NPM1 , WT1 , and C-KIT gene mutations between the two subgroups. Notably, patients with EMI at relapse had a higher frequency of KMT2A gene rearrangements (27.3% vs. 15.0%, p=0.0177) and a lower frequency of a normal karyotype (10.9% vs. 28.0%, p=0.0060). Unexpectedly, it is observed that patients with EMI at relapse presented with a lower frequency of FLT3-ITD mutation (9.4% vs. 21.5%, p=0.0308). Other karyotypes and gene rearrangements had similar occurrence rates in both subgroups (p >0.05) (Table 1).
Treatment and clinical outcomes
In the whole cohort, 106 patients (14.9 %) received stem cell transplantation after first complete remission (SCT in first CR), and 392 patients (55.0%) received gemtuzumab ozogamicin (GO) treatment. The proportions of SCT in the first CR and treatment with GO were similar between the group of patients with EMI at initial diagnosis and the group without EMI at initial diagnosis. However, patients with EMI at initial diagnosis had a significantly lower CR1 rate (67.5% vs. 76.8%, p=0.0299) and higher relapse rate (47.2% vs. 33.4%, p=0.0038) compared to patients without EMI at initial diagnosis, while there were no significant differences in CR2 rate and MRD negativity rate between the two groups (Table 2).
According to Kaplan-Meier analysis, the group with EMI at initial diagnosis had shorter event-free survival (EFS) (p=0.0037) and potentially shorter overall survival (OS) (p =0.0791) (Figs. 1A and 1B). However, in analyzing the overall survival among relapse patients, no significant difference (p =0.8686) was observed between those with and without EMI (Fig. 1E). Upon further analysis of patients with various sites of EMI, our finding revealed that individuals with MS (regardless of CNS involvement) demonstrated similar EFS and OS compared to those with CNS-only involvement (p >0.05) (Figs. 1C and 1D). Interestingly, among patients with EMI at relapse, those with MS exhibited a poorer OS compared to those with exclusive CNS involvement (p=0.0262) (Fig. 1F).
Table 2 . Treatment and therapeutic outcomes in AML patients with and without EMI at diagnosis.