1.Kinetic characteristics of T cell expansion in patients with B tumor after CAR19 T cell therapy
Lan DAI ; Ren MEI ; Wenhong SHEN ; Ziling ZHU ; Mengjie CAI ; Na′na PING ; Chongsheng QIAN ; Linyan HE ; Xia BAI ; Mingqing ZHU
Chinese Journal of Laboratory Medicine 2024;47(12):1435-1441
Objective:To investigate the proliferation kinetics of T cells in patients with B-cell hematologic malignancies who received CAR19 T cell therapy.Methods:Observational study. Flow cytometry was used to monitor the levels of CAR19+and CAR19-T cell expansion and the dynamic changes of T lymphocyte subsets before and after CAR19 T cell therapy. The 52 patients with B-cell hematologic malignancies (including 12 B-ALL and 40 NHL) who received CAR19 T cell therapy in the First Affiliated Hospital of Soochow University from November 2021 to December 2023 were recruited in this study. Patients were divided into complete response group and incomplete response group according to the efficacy evaluation criteria in the treatment guidelines for B-cell hematologic malignancies. T test or non-parametric rank sum test were used to compare the differences of CAR19+and CAR19-T cell subsets between the two groups.Results:At the peak of CAR19+T cell expansion, there was no statistic difference of CAR19+T cell subsets between the complete response group and the incomplete response group. After 6 months, the percentage of CD4+T cells (CD3+CD4+CD8-) in CAR19-T cells in patients was lower than the pre-treatment level(48.0+27.2,63.1+19.7,<0.01), and the percentages of CD197+CD45RA+and CD197-CD45RA-subsets recovered to the pre-treatment level, while the percentage of CD197-CD45RA+subset(4.2+3.0,21.1+15.6,<0.01) was lower than the pre-treatment level. The percentage of CD8+T cells (CD3+CD4-CD8+) returned to pre-treatment level after 6 months, CD197-CD45RA-subset in CD8+T cells returned to pre-treatment level, while CD197+CD45RA+subset(16.6+8.7,35.1+30.1,<0.01),CD197+CD45RA-subset(18.7+9.1,25.8+19.1,<0.01) were still lower than pre-treatment level.Conclusion:After CAR19 T cell treatment, there was no significant differences in the proportions of CAR19+T cell subsets in patients with different therapeutic effects. After treatment, the proportion of CAR19-CD3+CD4-CD8+cells recovered earlier than CD3+CD4+CD8-cells, and the dynamic changes of each subgroup were different. This therapeutic regimen has a great impact on the subpopulation of CAR19-T cells in vivo, and the reconstruction of such T cells takes a long time.
2.Kinetic characteristics of T cell expansion in patients with B tumor after CAR19 T cell therapy
Lan DAI ; Ren MEI ; Wenhong SHEN ; Ziling ZHU ; Mengjie CAI ; Na′na PING ; Chongsheng QIAN ; Linyan HE ; Xia BAI ; Mingqing ZHU
Chinese Journal of Laboratory Medicine 2024;47(12):1435-1441
Objective:To investigate the proliferation kinetics of T cells in patients with B-cell hematologic malignancies who received CAR19 T cell therapy.Methods:Observational study. Flow cytometry was used to monitor the levels of CAR19+and CAR19-T cell expansion and the dynamic changes of T lymphocyte subsets before and after CAR19 T cell therapy. The 52 patients with B-cell hematologic malignancies (including 12 B-ALL and 40 NHL) who received CAR19 T cell therapy in the First Affiliated Hospital of Soochow University from November 2021 to December 2023 were recruited in this study. Patients were divided into complete response group and incomplete response group according to the efficacy evaluation criteria in the treatment guidelines for B-cell hematologic malignancies. T test or non-parametric rank sum test were used to compare the differences of CAR19+and CAR19-T cell subsets between the two groups.Results:At the peak of CAR19+T cell expansion, there was no statistic difference of CAR19+T cell subsets between the complete response group and the incomplete response group. After 6 months, the percentage of CD4+T cells (CD3+CD4+CD8-) in CAR19-T cells in patients was lower than the pre-treatment level(48.0+27.2,63.1+19.7,<0.01), and the percentages of CD197+CD45RA+and CD197-CD45RA-subsets recovered to the pre-treatment level, while the percentage of CD197-CD45RA+subset(4.2+3.0,21.1+15.6,<0.01) was lower than the pre-treatment level. The percentage of CD8+T cells (CD3+CD4-CD8+) returned to pre-treatment level after 6 months, CD197-CD45RA-subset in CD8+T cells returned to pre-treatment level, while CD197+CD45RA+subset(16.6+8.7,35.1+30.1,<0.01),CD197+CD45RA-subset(18.7+9.1,25.8+19.1,<0.01) were still lower than pre-treatment level.Conclusion:After CAR19 T cell treatment, there was no significant differences in the proportions of CAR19+T cell subsets in patients with different therapeutic effects. After treatment, the proportion of CAR19-CD3+CD4-CD8+cells recovered earlier than CD3+CD4+CD8-cells, and the dynamic changes of each subgroup were different. This therapeutic regimen has a great impact on the subpopulation of CAR19-T cells in vivo, and the reconstruction of such T cells takes a long time.
3.Clinical observation of early-stage breast cancer after breast-conserving surgery with hypofractionated radiotherapy
Linjing ZHENG ; Dong YANG ; Bing HU ; Yinping DONG ; Lijun SUN ; Chongsheng XIA ; Baosheng LI ; Wei HUANG
Journal of International Oncology 2019;46(6):331-336
Objective To observe the long-term effect,adverse reaction and cosmetic outcome of early-stage breast cancer with hypofractionated whole-breast irradiation (HF-WBI) after breast-conserving surgery.Methods A total of 206 patients with stage 0-Ⅱ breast cancer after breast-conserving surgery were included in Shandong Cancer Hospital Affiliated to Shandong University from May 2014 to August 2017.According to radiotherapy fraction,patients were divided into HF-WBI group and conventional whole-breast irradiation (CF-WBI) group.In HF-WBI group,116 patients received whole-breast radiation to 42.56 Gy in 16 fractions followed by tumor bed boost of 9 Gy in 3 fractions or 10 Gy in 5 fractions.In CF-WBI group,90 patients received whole breast radiation to 50 Gy in 25 fractions followed by tumor bed boost of 10 Gy in 5 fractions.The 2-year local recurrence rate,2-year mortality rate,acute adverse reaction,late adverse reaction and cosmetic outcome of the two groups were analyzed.Results The 2-year local recurrence rates of HF-WBI group and CF-WBI group were 0.86% (1/116) and 2.22% (2/90) respectively,and there was no significant difference between the two groups (x2 =0.049,P =0.824).The 2-year mortality rates of the two groups were 0.86% (1/116) and 0 (0/90) respectively,and there was no significant difference (P > 0.999).There were 108 cases (93.1%) in HF-WBI group and 84 cases (93.3%) in CF-WBI group with grade 0-1 acute dermatitis,and 8 cases (6.9%) and 6 cases (6.7%) with grade 2-3 respectively,with no statistically significant difference (x2 =0.004,P =0.948).There were 97 cases (83.6%) in HF-WBI group and 79 cases (87.8%) in CF-WBI group with grade 0-1 bone marrow suppression,and 19 cases (16.4%)and 11 cases (12.2%) with grade 2-4 respectively,with no statistically significant difference (x2 =0.704,P =0.401).In the two groups,there were 1 case (0.9%) and 3 cases (3.3%) with grade 1-2 radiation pneumonitis,and 115 cases (99.1%) and 87 cases (96.7%) with no radiation pneumonitis respectively,and the difference was not statistically significant (x2 =1.626,P =0.202).There was 1 case (0.9%,1.1%) with grade 1 breast edema in each group,and 115 cases (99.1%) and 89 cases (98.9%) did not occur breast edema,with no statistically significant difference (x2 =0.033,P =0.857).In the late adverse reactions,there were 5 cases (4.3%) and 3 cases (3.3%) with skin pigmentation in HF-WBI group and CF-WBI group respectively.There were 2 cases (1.7%,2.2%) with grade 1 subcutaneous tissue fibrosis in each group,and there were 1 case (0.8%) and 2 cases (2.2%) with grade 1 pulmonary fibrosis respectively.The differences between the two groups were not statistically significant (x2 =0.000,P > 0.999;x2 =0.000,P > 0.999;x2 =0.049,P =0.824).The 6-month,1-year and 2-year cosmetic outcome good rates in HF-WBI and CF-WBI group were 96.5% (111/115) and 93.3% (84/90),92.1% (105/114) and 90.0% (81/90),91.4% (53/58) and 87.2% (41/47) respectively.The differences between the two groups were not statistically significant (x2 =0.526,P =0.468;x2 =0.277,P =0.599;x2 =0.476,P =0.490).The whole course of radiotherapy time in HF-WBI group was 25 days or 29 days,which was significantly shorter than the 40 days of CF-WBI group.Conclusion HF-WBI after breast-conserving surgery has the similar long-term effect,acute and late adverse reaction and cosmetic outcome compared with CF-WBI,and the treatment time is significantly shorter.It can be further promoted as the optimal adjuvant radiotherapy for early-stage breast cancer after breast-conserving surgery.
4.Research progress of hypofractionated whole breast irradiation after breast conserving surgery
Linjing ZHENG ; Yinping DONG ; Bing HU ; Chongsheng XIA ; Baosheng LI ; Wei HUANG
Journal of International Oncology 2018;45(9):570-573
Hypofractionated radiotherapy after breast conserving surgery has become a new standard treatment of early breast cancer. Clinical researches show that α/ β value of breast cancer is lower than that of other tumors,and the breast cancer is more suitable for hypofractionated radiotherapy. Hypofractionated radio-therapy has good economic benefits,and long-term follow-up results from a number of classical randomized con-trolled studies have shown that hypofractionated whole breast irradiation is effective and safe. With the extensive application of hypofractionated irradiation,this technology has been gradually extended to regional nodal irradia-tion,postmastectomy radiotherapy and breast ductal carcinoma in situ.
5.Effects of preoperative blood platelet-to-lymphocyte ratio on prognosis of non-small cell lung cancer patients after surgical resection
Changping SHAN ; Chongsheng XIA ; Yang YA ; Junye WANG ; Xiujun SU
Chinese Journal of Clinical Oncology 2014;(21):1374-1378
Objective:To investigate the correlation between preoperative blood platelet-to-lymphocyte ratio (PLR) and clinico-pathological features, as well as the effect of PLR on the prognosis of non-small cell lung cancer (NSCLC) patients after surgical resec-tion. Methods:Retrospective analysis was performed for 255 cases with histologically confirmed NSCLC that underwent curative re-section from January 2004 to December 2007. All patients were classified into two groups based on the median value of PLR. The rela-tionship between PLR and clinicopathological features was studied. Univariate and multivariate analyses were performed to assess the prognostic effect of preoperative PLR. Results:The median value of preoperative PLR was 130 (range:45.45 to 272.66). Based on the cut-off value of 130, all patients were divided into two groups:low PLR (≤130, n=127) and high PLR (>130, n=128). PLR was corre-lated with tumor site, T stage, and clinical stage. Five-year survival rates of low and high PLR patients were 49.6%and 33.6%, respec-tively, which indicated a statistically significant difference (χ2=12.577, P<0.001) between the two groups. Univariate analysis showed that smoking status, histological differentiation, clinical stage, T stage, N stage, postoperative adjuvant therapy and PLR were associat-ed with survival (P<0.05 for all). Multivariate analysis identified N stage, postoperative adjuvant therapy, and PLR as independent prog-nostic factors of all the patients. In addition, stratified analysis showed that the five-year survival rate of the low PLR group was higher than that of the high PLR group with or without lymph node metastasis, and the differences were statistically significant (P=0.020 and 0.037). Conclusion:An elevated blood preoperative PLR indicates poor prognosis in NSCLC patients. Preoperative PLR is an indepen-dent prognostic factor of NSCLC after curative resection.

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