Purpose: To investigate the role of soluble programmed cell death ligand 1 (sPD-L1) protein in plasma of patients with Peripheral T-cell lymphoma (PTCL). Methods: In total, 80 patients with newly diagnosed PTCL and 75 healthy controls were enrolled. Levels of sPD-L1 were measured by ELISA at diagnosis and after 3–8 courses of chemotherapy. The expression of PD-L1 in tumor tissues from nine PTCL patients was also detected. Results: sPD-L1 was higher in PTCL patients at diagnosis compared to healthy subjects (P < 0.0001). Patients in the intermediate/high-risk disease group had a higher level of sPD-L1 than patients in the low-risk group (P = 0.0003). Elevated sPD-L1 (≥176.30 pg/ml) was the only biomarker for PTCL that retain statistical significance in multivariate analysis. Patients in the low-risk group with sPD-L1 ≥ 176.30 pg/ml had an adverse prognosis. Histological analysis showed that the expression of PD-L1 in tissues was positively correlated with sPD-L1 levels in plasma (Spearman = 0.9177, P = 0.0013). Conclusions: sPD-L1 is a sensitive biomarker predicting clinical outcomes in PTCL.

Our objective was to evaluate the efficacy and safety of intravenous (IV) sotalol in the treatment of incessant tachyarrhythmias in children with normal cardiac function. Eighty-three children admitted to hospital from October 2011 to December 2014 were treated with IV sotalol or IV sotalol plus IV propafenone. The time to conversion to sinus rhythm and maintaining sinus rhythm were evaluated. Blood pressure, heart rate, QTc, PR intervals, and rhythm were monitored; 50 patients (60%) were converted to sinus rhythm with IV sotalol; time to conversion was 12.0 ± 18.0 hours; 12 additional patients (15%) were converted with IV sotalol combined with IV propafenone; time to conversion was 13.1 ± 17.6 hours. A total of 62 patients (75%) were converted. Success rates of IV sotalol for different tachycardias were similar, whereas the time to conversion differed. The time to conversion for atrioventricular reentrant tachycardia was shorter than atrial tachycardia or atrial flutter (p <0.05). QTc prolongation (from 253 to 486 ms and from 398 ms to 500 ms) was seen in 2 patients (2%) within 48 hours after conversion. The QTc reverted to normal range at 48 and 144 hours, respectively, after withdrawal of IV sotalol. A 1 month old with atrial flutter developed bradycardia (7:1 atrioventricular conduction) 5 minutes after IV sotalol, and heart rate increased gradually after drug withdrawal. No other adverse effects were observed. In conclusion, IV sotalol can be safely and effectively used to terminate pediatric tachycardias in patients with normal cardiac function. No proarrhythmic or significant toxicities were detected. Close monitoring of QTc and heart rate is required after IV sotalol. Adding IV propafenone to IV sotalol in resistant cases enhance conversion.

Prizloncabtagene autoleucel (prizlon-cel), a novel bispecific chimeric antigen receptor T cell, targets and eliminates CD19/CD20-positive tumor cells. This phase 1, open-label study investigated the safety and efficacy of prizlon-cel in patients with relapsed/refractory B-cell non-Hodgkin lymphoma (R/R B-NHL). Patients with CD19 and/or CD20-positive R/R B-NHL received a 3-day lymphodepletion (cyclophosphamide: 300 mg/m2 per day; fludarabine: 30 mg/m2 per day) followed by an IV dose of prizlon-cel. The primary end points were dose-limiting toxicity (DLT) and incidence and severity of treatment-emergent adverse events (TEAEs). Secondary end points included overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Of the 48 patients infused prizlon-cel, 44 had large B-cell lymphoma (LBCL). No patient experienced DLT. Cytokine release syndrome occurred in 93.8% of the patients, with only 1 case of grade 3. Immune effector cell-associated neurotoxicity syndrome occurred in 6.3% of patients, with no grade 3 or higher events. The most common grade 3 or higher TEAEs were neutropenia (83.3%) and leukopenia (50%). The ORR and complete response (CR) rates in all patients were 91.5% and 85.1%, respectively, and in LBCL patients, ORR was 90.7% with 86.0% CR. With median follow-up of 30.0 months, median DOR, PFS, and OS were all not reached. Kaplan-Meier estimate of 2-year DOR, PFS, and OS rates were 66.0%, 62.6%, and 76.5%, respectively. Prizlon-cel had a favorable safety profile and a high and durable response in patients with R/R B-NHL, suggesting a promising treatment option for patients with R/R B-NHL. These trials were registered at www.clinicaltrials.gov as #NCT04317885, #NCT04655677, #NCT04696432, and #NCT04693676.

CAR-T cell therapy did not achieve the desired efficacy in some patients with diffuse large B-cell lymphoma (DLBCL). We conducted single-cell RNA and TCR sequencing as well as methylation chip profiling of peripheral blood samples in DLBCL patients. Patients who achieved complete remission (CR) showed an upward trend in T-cell levels, especially CD8-effector T cells. The responders exhibited T-cell clone expansion, more active T-cell transformation, and frequent cell communication. Highly expressed genes in the CR group were enriched in functions like leukocyte-mediated cytotoxicity and activation of immune response, while the non-CR group was enriched in pathways related to DNA damage and P53-mediated intrinsic apoptotic. More differentially methylated probes (DMPs) were identified in the baseline of the non-CR group (779 vs 350). GSEA analysis revealed that the genes annotated by DMPs were associated with cellular immune functions in T cells, including the generation of chemokines, leukocyte-mediated cytotoxicity, and cell-killing functions. The genes with low expression in the non-CR group exhibited a high methylation status. There is heterogeneity in the cellular, molecular, and epigenetic characteristics of host T cells in patients with different clinical outcomes. Intrinsic defects in T cells are important factors leading to poor efficacy of CAR-T therapy.