关键词: 费城染色体阳性, 急性淋巴细胞白血病, 二代测序, 基因变异谱, 儿童

Abstract:

Objective To detect the concomitant gene variants other than the BCR::ABL1 fusion gene in pediatric patients diagnosed with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph⁺ ALL) using next-generation sequencing (NGS) technology, and to explore the correlation between these variations and early treatment response as well as prognosis. Methods A retrospective analysis was performed on the clinical data and NGS detected hematological malignancy-related genetic variation results of pediatric patients with newly diagnosed Ph⁺ ALL from January 2020 to July 2025. Based on the status of IKZF1 gene deletion and the presence of CDKN2A/B or PAX5 deletions, the patients were divided into three groups: IKZF1plus group, isolated IKZF1 group, and IKZF1 negative group. Early treatment response was evaluated by the negative conversion rate of minimal residual disease (MRD) on day 33 of induction chemotherapy and the achievement rate of major molecular response (MMR). Prognosis was assessed by the rate of event-free survival (EFS), disease-free survival (DFS), cumulative incidence of relapse (CIR), and overall survival (OS). Results A total of 25 pediatric patients with Ph⁺ ALL who underwent NGS detection, including 18 males (72%) and 7 females (28%), with a median age of 9 (4-16) years at initial diagnosis. Concomitant genetic abnormalities were detected in 21 patients (84%), among which IKZF1 deletion was the most prevalent, occurring in 18 cases (72%). Among all enrolled children, the MRD negative conversion rate on day 33 of induction chemotherapy was 40%, and the MMR achievement rate was 44%. The median follow-up duration was 38 months (range: 2-82 months). The 3-year EFS rate was 43.5%, the 3-year DFS rate was 81.2%, the 3-year CIR was 26.5%, and the 3-year OS rate reached 100%.Patients were stratified into three groups according to concomitant genetic profiles: the IKZF1plus group (3 cases, 12%), the isolated IKZF1 deletion group (15 cases, 60%), and the non-IKZF1 abnormality group (7 cases, 28%). No statistically significant differences were observed in baseline clinical characteristics among the three groups (P>0.05). There were no significant intergroup differences in the bone marrow MRD negative conversion rate and MMR achievement rate on day 33 of induction chemotherapy (χ²=2.90, χ²=0.87, P>0.05). Similarly, no statistical differences were found in EFS, DFS and CIR across the three cohorts (χ²=0.07, χ²=3.19, χ²=2.77, P>0.05). Conclusion NGS can efficiently delineate the genetic variation spectrum of pediatric Ph⁺ ALL patients. IKZF1 deletion was the most common genetic abnormality. Neither IKZF1 nor IKZF1plus subtype has a significant impact on early molecular remission and long term survival within the limited sample size and followup duration.

Key words: Philadelphia chromosome positive, acute lymphoblastic leukemia, next-generation sequencing, gene variants, child