[Analysis of local reactions and efficacy of CD19 chimeric antigen receptor-modified T cells therapy in recurrent/refractory B-cell lymphoma with >7.5 cm lesions].

Objective: To observe the local reactions and efficacy of CD19 CAR-T therapy in recurrence/refractory B-cell non-Hodgkin's lymphoma (R/R NHL) patients with >7.5 cm lesions. Methods: 32 R/R NHL patients with >7.5 cm lesions were enrolled and injected with CD19 CAR-T cells. Flow cytometry was used to detect and observe the amplification of CD19 CAR-T cells in vivo. Enzyme-linked immunosorbent assay (ELISA) was used to detect cytokines in peripheral blood of patients. The side effects of CD19 CAR-T cell therapy included systemic side effects and local reactions of tumor. The local side effects were observed by Ultrasound, Computed tomography and Magnetic resonance imaging. Treatment options included glucocorticoid, interleukin-6 antibody and drainage of exudate. Overall response rate (ORR) and overall survival rate (OS) were observed. Results: ①Among the 32 patients, CR (40.63%) , PR (31.25%) and ORR (71.88%) were 13, 10 and 23, respectively. ②In all 23 patients received ORR, 13 patients had grade 1-2 CRS, while 10 patients had grade 3-4 CRS. All the 9 patients in the SD+PD group had grade 1-2 CRS (P=0.030) . ③A total of 15 patients with tumor local reactions, included 9 patients with CR, 5 patients with PR and 1 patient with SD. The local reactions of the tumor included that the diameter of the superficial lesions increased with redness, swelling and heat pain. The deep lesions presented abdominal pain, abdominal distension, suffocation and local pain, and burning of the tumor. The deep lesions were enlarged or accompanied by local edema. The local exudative lesions were found in the abdominal cavity and pleural cavity. ④ Peak proportion of CD19 CAR-T cells in ORR group was higher than that of in SD+PD group[16.8% (5.3%-48.2%) vs 2.9% (1.5%-5.7%) , z=-4.297, P<0.001]. The peak proportion of CD19 CAR-T cells in ORR group with local reactions was higher than that of in patients without local reactions [22.2% (10.5%-48.2%) vs 12.6% (5.3%-21.6%) , z=-3.213, P=0.001]. The peak proportion of CD19 CAR-T cells in multiple lesion group was higher than that of in single lesion group [35.8% (1.5%-48.2%) vs 16.8% (10.5%-18.5%) , z=-2.023, P=0.040]. ⑤Occurrence of local reactions and tumor shrinkage time were both delayed compared with systemic side effects. ⑥In the ORR group, the OS of patients with tumor local reactions was longer than that of patients without tumor local reactions, but there was no difference in the two groups (75% vs 34.6%, P=0.169) . Conclusions: CD19 CAR-T cell therapy in R/R NHL patients with >7.5 cm lesions might cause tumor local reactions later than systemic side effects. Clinicaltrial:: ChiCTR1800018059.

[Relative analysis of platelet activation with bleeding risk in patients with primary immune thrombocytopenia].

Objective: To study the relationship between platelet activation and the degree of bleeding in patients with primary immune thrombocytopenia (ITP) . Methods: 43 patients with ITP were assessed based on ITP-BAT bleeding grading system. Platelet membrane glycoproteins (GP) Ⅰb, GPⅡb/Ⅲa and P-selectin expression were detected by flow cytometry analysis with and without adenosine diphosphate (ADP) stimulation. Association of platelet activation with platelet count, immature platelet fraction (IPF) , bleeding severity were evaluated. Results: GPⅡb/Ⅲa and P-selection expressions on unstimulated platelet in ITP patients were higher than those in healthy controls (65.69±10.73 vs 7.16±0.99, t=4.130, P<0.001; 15.43±1.41 vs 12.55±1.03, t=2.070, P=0.043, respectively) , and GPⅠb expression was lower than that in healthy controls (240.11±24.93 vs 295.11±22.15, t=2.417, P=0.020) . Comparatively to healthy individuals, following ADP stimulation, GPⅡb/Ⅲa expression in ITP patients increased (133.96±12.17 vs 39.67±4.99, t=5.256, P<0.001) , whereas GPⅠb and P-selection expressions decreased (37.09±3.94 vs 109.77±23.66, t=3.901, P<0.001; 149.06±19.14 vs 205.73±21.00, t=2.070, P=0.043, respectively) . ADP-stimulated GPⅠb, ADP-stimulated and unstimulated P-selection, proportion of GPⅠb, P-selection levels with/without ADP stimulation were significantly associated with platelet counts (P<0.05) . ADP-stimulated P-selection and proportion of P-selection levels with/without ADP stimulation were significantly associated with IPF (P<0.05) . There were significant differences in the expressions of unstimulated P-selection, ADP-stimulated P-selection, ADP-stimulated GPⅠb stratified by bleeding grades (P<0.05) . The ratios of P-selection, GPⅡb/Ⅲa and GPⅠb with/without ADP stimulation in ITP patients were significantly different among various bleeding grades (P<0.05) . Higher proportion of GPⅠb with/without ADP stimulation was associated with higher risk of bleeding (OR=3.05, P=0.011) . Lower proportion of GPⅡb/Ⅲa and P-selection with/without ADP was associated with higher risk of bleeding (OR=0.32, P=0.023; OR=0.04, P=0.006, respectively) . Conclusion: Platelet activation index could accurately assess the degree of bleeding in patients with ITP, and also be used as the observation index and reference index for treatment.