ABSTRACT
Objective: To explore the prognostic value of circulating tumor DNA (ctDNA) testing in patients with refractory/relapsed diffuse large B-cell lymphoma (R/R DLBCL) undergoing chimeric antigen receptor T-cell (CAR-T) therapy, and to guide the prevention and subsequent treatment of CAR-T-cell therapy failure. Methods: In this study, 48 patients with R/R DLBCL who received CAR-T-cell therapy at the First Affiliated Hospital of Zhejiang University School of Medicine between December 2017 and March 2022 were included. Furthermore, ctDNA testing of 187 lymphoma-related gene sets was performed on peripheral blood samples obtained before treatment. The patients were divided into complete remission and noncomplete remission groups. The chi-square test and t-test were used to compare group differences, and the Log-rank test was used to compare the differences in survival. Results: Among the patients who did not achieve complete remission after CAR-T-cell therapy for R/R DLBCL, the top ten genes with the highest mutation frequencies were TP53 (41%), TTN (36%), BCR (27%), KMT2D (27%), IGLL5 (23%), KMT2C (23%), MYD88 (23%), BTG2 (18%), MUC16 (18%), and SGK1 (18%). Kaplan-Meier survival analysis revealed that patients with ctDNA mutation genes >10 had poorer overall survival (OS) rate (1-year OS rate: 0 vs 73.8%, P<0.001) and progression-free survival (PFS) rate (1-year PFS rate: 0 vs 51.8%, P=0.011) compared with patients with ctDNA mutation genes ≤10. Moreover, patients with MUC16 mutation positivity before treatment had better OS (2-year OS rate: 56.8% vs 26.7%, P=0.046), whereas patients with BTG2 mutation positivity had poorer OS (1-year OS rate: 0 vs 72.5%, P=0.005) . Conclusion: ctDNA detection can serve as a tool for evaluating the efficacy of CAR-T-cell therapy in patients with R/R DLBCL. The pretreatment gene mutation burden, mutations in MUC16 and BTG2 have potential prognostic value.
Subject(s)
Humans , Prognosis , Receptors, Chimeric Antigen , Circulating Tumor DNA/genetics , Feasibility Studies , Lymphoma, Large B-Cell, Diffuse/therapy , Lymphoma, Non-Hodgkin , Mutation , Cell- and Tissue-Based Therapy , Retrospective Studies , Immediate-Early Proteins , Tumor Suppressor ProteinsABSTRACT
OBJECTIVE@#To compare different types of peritoneal fibrosis models in rats.@*METHODS@#Thirty-four SD rats were divided into 5 groups: control group (Group 1), normal saline group (Group 2), high glucose group (4.25% peritoneal dialysate, 4.25% PDF, Group 3), high glucose + lipopolysaceharides (LPS) group (4.25% PDF + LPS, Group 4), high glucose + erythromycin group (4.25% PDF + lactobionate erythromycin, Group 5). A 2-hour peritoneal equilibration test (PET) was performed after 5 weeks. Then animals were humanely killed. Dialysate-to-plasma urea ratio (D/ Purea), glucose reabsorption (D2/D0), net ultrafiltration (UF) volume were determined. The level of fibronectin in peritoneal tissues was measured by immunohistochemical method. Peritoneal membrane histology was evaluated by light microscopy.@*RESULTS@#The D2/D0 ratio and net ultrafiltration volume in Groups 3, 4, and 5 were significantly lower than those in Groups 1 and 2 (P < 0.05) . The D/Purea ratio in Groups 3, 4 and 5 were significantly higher than that in Groups 1 and 2 (P < 0. 05 ). The level of fibronectin in Groups 3, 4 and 5 were significantly higher than that in Groups 1 and 2 (P < 0.05 ).@*CONCLUSION@#Different types of peritoneal fibrosis models in rats has been established. The best model is high clusion glucose + erythromycin.