ABSTRACT
Objective:To investigate the relationship between the levels of serum cytokines and chemokines and the prognosis of patients with acute B-ALL after receiving chimeric antigen receptor (CAR)-T cell immunotherapy and acute graft-versus-host disease (aGVHD) in patients after bridging allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:According to the case-control principle, Forty-two patients with B-ALL who received CD19-CAR-T cell immunotherapy bridged to allo-HSCT at Heibei Yanda Ludaopei Hospital from September 18, 2019 to May 9, 2022 were enrolled. Mann-Whitney U test was used to compare the changes of aGVHD-related cytokines and chemokine levels between CAR-T cell immunotherapy and bridging transplantation in different patients at the same time. Their plasma levels of cytokines and chemokines related to aGVHD were monitored at the day before CAR-T therapy and after CAR-T treatment at day 4, 7,14,21,28. The receiver operating characteristic curve was drawn to evaluate the predictive value of cytokines and chemokines in predicting the occurrence and the death of aGVHD patients. Kaplan-Meier method and Log-rank tests were used for Overall survival (OS) analysis. Results:Twenty-four of total 42 patients had aGVHD, of which 11 patients died and 31 patients survived. There was no significant difference in cytokines and chemokines between the aGVHD group and the non-aGVHD group on the day before CAR-T cell treatment. According to statistical analysis, the serum Elafin levels of aGVHD group was higher than that of non-aGVHD group at the 21st day [4 482 (2 811, 6 061) ng/L vs 2 466 (1 948, 3 375) ng/L, Z=3.145, P=0.001] and the 28st day [4 391 (2 808, 5594) ng/L vs 2 463 (1 658, 2 830) ng/L, Z=2.038, P=0.048] separately. At the 14th day, serum cytokines and chemokines levels between the two group were as follows,MIP-1 α [21.02 (12.36, 30.35) ng/L vs 5.56 (3.64, 10.79) ng/L], sCD25 [422.47 (257.99, 1 233.78) IU/ml vs 216.11 (133.75,457.39) IU/ml], Elafin [4 101 (2 393, 5 006) ng/L vs 2 155 (1 781, 3 033) ng/L], IL-6 [119.08 (23.97, 183.43) ng/L vs 8.39 (2.91, 17.42) ng/L] and IL-8 [13.56 (12.50, 24.52) ng/L vs 2.83 (1.73,6.87) ng/L] were at higher levels ( Z=2.653, P=0.007; Z=2.176, P=0. 030; Z=2.058, P=0.041; Z=3.329, P<0.001; Z=3.162, P=0.001). The KM survival curve showed that the cumulative survival rates of patients with higher serum levels of MIP-1α, sCD25, Elafin, IL-6 and IL-8 were lower than those with low levels at day 14, and the difference was statistically significant (χ 2=12.353, 4.890, 6.551, 10.563, 20.755, P<0.05). Conclusion:The outcomes of patients treated with CAR-T cell therapy bridged to allo-HSCT was correlated with serum MIP-1α, sCD25, Elafin, IL-6 and IL-8 levels after receiving CAR-T therapy. High concentrations of MIP-1α, sCD25, Elafin, IL-6 and IL-8 suggest poor prognosis and can be used as biomarkers to suggest appropriate clinical selection of therapy.
ABSTRACT
Objective:To investigate the significance of multicolor flow cytometry (MFC) monitoring of minimal residual disease (MRD) in the course of allogeneic hematopoietic stem cell transplantation (allo-HSCT) after CD19-chimeric antigen receptor(CAR)-T cell immunotherapy for patients with refractory, relapsed B-cell acute lymphoblastic leukemia (r/r B-ALL).Methods:37 patients with r/r B-ALL admitted to Hebei Yanda Lu Daopei Hospital from January to July 2019, aged 15 (6, 19) years old, including 24 males and 13 females, were treated with CD19-CAR-T cell immunotherapy bridging allo-HSCT. MFC with cytoplasmic CD79a antibody to set up B-cell gates was used to monitor patients′ bone marrow (BM), cerebrospinal fluid (CSF), and tissue samples on day 0 (prior to the CAR-T cell immunotherapy), day 15, day 28 post CAR-T cell immunotherapy, and post transplantation.The MRD values of these samples were analyzed to evaluate the residual tumor cells and metastasis. The killing effect of the CAR-T cells was evaluated by the recovery of CD19+B cells before transplantation and the period between the timepoint when CD19+B cells was recovered and the timepoint when CAR-T cells were infused. Peripheral blood CAR-T cells were counted at different time points. Statistic analysis was performed by Kaplan-Meie assay and Log-rank test to analyze the difference of univariate cumulative survival.Results:(1)Among the 37 patients, 8 died and 29 survived. 5 patients relapsed after transplantation, of which 4 relapsed patients died and 1 survived. (2)MFC MRD negative remission rate of the death group was lower than that of the survival group at the following time points: post-CAR-T therapy and prior to transplantation (5/8 vs. 28/29, χ 2=7.540, P=0.006); day 15 of the CAR-T cell reinfusion (3/8 vs. 24/29, χ 2=6.512, P=0.011); day 28 of the reinfusion (3/8 vs. 276/29, χ 2=10.065, P=0.002). The probability of extramedullary MFC MRD positive tumor infiltration in the death group was higher than that in the survival group(7/8 vs. 14/29, χ 2=3.931, P=0.047). After CAR-T cell immunotherapy, the recovery period of CD19-positive cells in the death group, or the time for CAR-T cells to kill CD19-positive cells, was shorter than that in the survival group [42.00 days(30.00,49.00) vs. 55.00 days(41.50,73.50), Z=0.022, P=0.020]. Conclusion:The positive results of MRD by MFC at the following timepoints may predict unfavorable outcomes, such as post-CAR-T therapy and prior to transplantation, day 15 and 28 of the CAR-T cell immunotherapy, which may provide some guidance for clinical management.
ABSTRACT
Objective:To investigate the application effects of MOTOmed in stepped individualized rehabilitation intervention of older adult patients with post-stroke hemiplegia.Methods:A total of 130 older adult patients with post-stroke hemiplegia who received treatment in the Affiliated People's Hospital of Ningbo University from June 2019 to June 2021 were included in this study. They were randomly assigned to undergo either stepped individualized rehabilitation intervention with MOTOmed training system (observation group, n = 65) or routine rehabilitation intervention (control group, n = 65) for 1 month. Before and after intervention, the Fugl- Meyer Assessment score, Berg Balance Scale score, Functional Ambulation Category scale score, modified Ashworth scale score, and modified Barthel Index, Self-Perceived Burden Scale score, nerve growth factor, brain-derived neurotrophic factor and neurotrophin 3 levels were compared between the two groups. Results:After intervention, Fugl-Meyer Assessment and Berg Balance Scale scores in the observation groups were (75.48 ± 6.54) points and (48.55 ± 5.18) points, which were significantly greater than (72.55 ± 6.33) points and (46.50 ± 4.79) points in the control group ( t = 2.59, 2.34, both P < 0.05). Functional Ambulation Category scale score in the observation group was significantly higher than that in the control group [(3.22 ± 0.43) points vs. (3.05 ± 0.39) points, t = 2.36, P < 0.05). Modified Ashworth scale score in the observation group was significantly lower than that in the control group [(1.23 ± 0.24) points vs. (1.33 ± 0.26) points, t = 2.27, P < 0.05). Modified Barthel Index score in the observation group was significantly higher than that in the control group [(59.32 ± 5.18) points vs. (57.33 ± 4.92) points, t = 2.24, P < 0.05]. There was no significant difference in Self-Perceived Burden Scale score between the two groups ( t = 1.64, P > 0.05). Nerve growth factor level in the observation group was significantly higher than that in the control group [(12.93 ± 2.31) ng/L vs. (12.06 ± 2.29) ng/L, t = 2.15, P < 0.05]. There were no significant differences in brain-derived neurotrophic factor and neurotrophin 3 levels between the two groups ( t = 0.91, 1.25, both P > 0.05). Conclusion:The stepped individualized rehabilitation intervention with MOTOmed training system can greatly improve the limb function, balance ability, walking ability and self-care ability, reduce muscle tension, and increase nerve growth factor level in older adult patients with post-stroke hemiplegia, which are conducive to the rehabilitation and prognosis of post-stroke hemiplegia.
ABSTRACT
@#ObjectiveTo test and verify whether Ba-alginate-Poly-L-Ornithine-Alginate microcapsules(B-PLO-A) can improve the physical properties and biocompatibility of the traditional BPA microcapsules.MethodsThe B-PLO-A and Ba-alginate-Poly-L-lysine-alginate（B-PLL-A） microcapsules were made by the static generator. The physical property of the microcapsules was evaluated by observing the morphological changes of the microcapsules in the hypotonic environment, changes in diameter of microcapsules in vitro culture and calculating broken microcapsules ratio by shaking method. The biocompatibility was observed by transplanting into peritoneal cavity of rat.ResultsB-PLO-A microcapsules are stronger and more stable in a hypotonic environment than B-PLL-A microcapsules. After 96 h mechanism shaking, the unbroken microcapsules ratio of B-PLO-A and B-PLL-A microcapsules were (99.3±1.0)% and (96.2±1.5)% respectively. The microcapsules were retrieved from peritoneal cavity of rat at 2, 4 and 8 weeks after transplantation, most of the microcapsules were of integrity, rotundity, and surface smooth without obviously bundled by connective tissue. 8 weeks after transplantation the intact microcapsules ratio of B-PLO-A and B-PLL-A microcapsules were (97.3±2.1)% and (95.4±2.4)% respectively.ConclusionB-PLO-A microcapsules as a whole have bettermechanical strength compared with B-PLL-A microcapsules, while maintaining a good biocompatibility.