CORRELATION BETWEEN SOMATIC MUTATIONS AND PROGNOSIS IN PEDIATRIC MATURE B‐CELL LYMPHOMA

Abstract

Introduction: To investigate the prognostic factors of childhood mature B-cell lymphoma (MBL), especially the significance of somatic mutations in the clinical features and prognosis, by analyzing the clinical chartacteristics, genetic mutation results and prognosis of 133 children with MBL. Methods: Children and adolescents (≤18 years old) with MBL who were admitted from November 2017 to February 2023 were enrolled, and patients with somatic mutations were detected using next-generation sequencing (NGS). The diagnosis includes the completion of pathological examination and center consultation, and the staging is based on the international children's St. Jude staging system, primary patients were treated with the modified LMB89/96 protocol. Refractory or recurrent (r/r) patients were treated with second-line chemotherapy based on ICE and/or CAR-T-cell sequential therapy with different B-cell targets. The factors related to curative effect and prognosis, especially the correlation between the gene mutation spectrum and prognosis, were analyzed. Results: The mutant gene spectrum of 133 patients is shown in Fig.a. According to the time of specimen collection, there were 77 cases of initial diagnosis (initial treatment group) and 56 cases of r/r patients (r/r group). The clinical feature and survival of the 133 patients are summarized in Figure b, c, d, e (P < 0.001) and g. The results showed that patients with a large tumor focus, serous cavity effusion and delayed chemotherapy during treatment had significant difference in prognosis and significantly shortened survival. The top three genes in the initial treatment group were ID3 (53%), TP53 (47%), and CCND3 (30%) (Figure h). The top three genes in the r/r group were TP53 (82%), ID3 (58%), and ARID1A (40%) (Figure j). TP53 was significantly different between the initial treatment group and r/r patients (P < 0.001). Of the 133 patients grouped by efficacy, 70 progressed/relapsed, and 59/70 received CAR T therapy, with an overall response rate (ORR) of 83%. Survival analysis is shown in the figure f. A total of 11/70 patients received second-line chemotherapy, and only 1 patient survived to receive treatment. Compared with second-line chemotherapy, CAR T-cell treatment significantly improved the survival rate (P = 0.008). ARID1Awas significant in patients with poor prognosis after CAR T therapy (P = 0.00081) (Figure k). Keywords: Chemotherapy, Diagnostic and Prognostic Biomarkers, Non-Hodgkin (Pediatric, Adolescent, and Young Adult) No conflicts of interests pertinent to the abstract.