Efficacy and side effects of anti-CD19 CAR T-cell therapy in patients with relapsed/refractory gastrointestinal lymphoma.

INTRODUCTION: Although anti-CD19 chimeric antigen receptor (CAR) T cell therapy was approved as a very effective salvage strategy in relapsed/refractory (R/R) B cell lymphoma, the experience in R/R gastrointestinal (GI) lymphoma is still insufficient. METHODS: We summarized the efficacy and side effects of anti-CD19 CAR T-cell therapy in 12 patients with R/R GI lymphoma. Based on literature, the R/R GI lymphoma patients were divided into subgroups with different characteristics: Bulky/No bulky disease, Gastric/Gastrointestinal involvement, Gastrointestinal/Combined extra-gastrointestinal lesions, Ulcer/Lumps or nodules type, With/without gastrointestinal bleeding. RESULTS: The objective response rate (ORR) was 66.67% in these 12 patients. The ORR was 83.33% in no bulky disease group, 80.00% in gastric involvement group, 100.00% in ulcer type group, and 80.00% in no gastrointestinal bleeding group. The CR rate was 33.33% in these 12 patients. The CR was 50.0% in no bulky disease group, 60.00% in gastric involvement group, and 80.00% in ulcer type group. The PFS and OS rate of the 12 patients at 6 months after infusion were 54.55% and 58.33%, respectively. The overall survival (OS) at 6 months was higher in no bulky disease group. There was no difference of the OS or the progression free survival (PFS) at 6 months between the other groups. The mean peak of CAR-T cells and Cytokine Release Syndrome (CRS) grade were higher in gastrointestinal lesions group. The mean peak of IFN-γ and CRS grade were higher in gastrointestinal bleeding group. Four out of six patients in group of gastrointestinal lesions group were patient with high tumor burden. Patients with gastrointestinal involvement only were at higher risk for gastrointestinal bleeding. CONCLUSIONS: The ORR and CR of high tumor load, gastrointestinal involvement, lumps or nodules type and gastrointestinal bleeding group were lower. The CRS grade was higher in gastrointestinal lesions group and in gastrointestinal bleeding group. Patients with gastrointestinal involvement only were at higher risk for gastrointestinal bleeding.

Integrated Analysis of mRNA and Non-coding RNA Transcriptome in Pepper (Capsicum chinense) Hybrid at Seedling and Flowering Stages.

Pepper is an important vegetable in the world. In this work, mRNA and ncRNA transcriptome profiles were applied to understand the heterosis effect on the alteration in the gene expression at the seedling and flowering stages between the hybrid and its parents in Capsicum chinense. Our phenotypic data indicated that the hybrid has dominance in leaf area, plant scope, plant height, and fruit-related traits. Kyoto Encyclopedia of Genes and Genomes analysis showed that nine members of the plant hormone signal transduction pathway were upregulated in the seedling and flowering stages of the hybrid, which was supported by weighted gene coexpression network analysis and that BC332_23046 (auxin response factor 8), BC332_18317 (auxin-responsive protein IAA20), BC332_13398 (ethylene-responsive transcription factor), and BC332_27606 (ethylene-responsive transcription factor WIN1) were candidate hub genes, suggesting the important potential role of the plant hormone signal transduction in pepper heterosis. Furthermore, some transcription factor families, including bHLH, MYB, and HSF were greatly over-dominant. We also identified 2,525 long ncRNAs (lncRNAs), 47 micro RNAs (miRNAs), and 71 circle RNAs (circRNAs) in the hybrid. In particular, downregulation of miR156, miR169, and miR369 in the hybrid suggested their relationship with pepper growth vigor. Moreover, we constructed some lncRNA-miRNA-mRNA regulatory networks that showed a multi-dimension to understand the ncRNA relationship with heterosis. These results will provide guidance for a better understanding of the molecular mechanism involved in pepper heterosis.

Complete plastome sequence of Euphorbia milii Des Moul. (Euphorbiaceae).

Euphorbia milii (Euphorbiaceae) grows as a scrambling shrub with many branches. Here, we report and characterize the complete plastome of E. milii in an effort to provide genomic resources useful for promoting its systematic research. The plastome of E. milii is found to possess a total length of 160,806 bp with the typical quadripartite structure of angiosperms, contains two Inverted Repeats (IRs) of 26,695 bp, a Large Single-Copy (LSC) region of 90,211 bp and a Small Single-Copy (SSC) region of 17,205 bp. The plastome contains 114 genes, consisting of 80 unique protein-coding genes, 30 unique tRNA genes and four unique rRNA genes. The overall A/T content in the plastome of E. milii is of 64.10%. The phylogenetic analysis indicated that E. milii is close to E. tirucalli within Euphorbiaceae in this study. The complete plastome sequence of E. milii will provide a useful resource for the conservation genetics of this species as well as for the phylogenetic studies of Euphorbiaceae.

[Clinical Effectiveness of Decitabine Combined with Reduced FLAG Regimen in the Treatment of Senile Patients with High-Risk Acute Myeloid Leukemia].

OBJECTIVE: To explore the efficacy and adverse reactions of decitabine combined with reduction FLAG regimen on the senile patients with high-risk AML. METHODS: 12 senile patients with high-risk AML received decitabine combined with reduced FLAG regimen (decitabine 20 mg/m2, intravenous drip, qd, d 1-5; fludarabine 30 mg/m2, intravenous drip lasts 30 min, qd, d 3-6; Ara-C 1 g/m2, intravenous drip, qd, d 3-6; and G-CSF 300 µg/d, subcu- taneous injection, d 2 to neutrophils reached the lowest return to＞1.0×109/L) in our study. The efficacy and adverse reactions of this regimen were analyzed. RESULTS: 9 patients achieved complete remission(CR) after one course of decitabine combined with reduced FLAG regimen, 2 patients achieved partial remission (PR) and 1 patient reached a stable disease (SD). The overall response rate was 92%. The median follow-up period was 7.4 months ranged from 3 to 12 months. The median survival time for all patients was 6.4 months. The main treatment-related toxicities were myelosuppression and infection due to neutropenia. Severe non-hematologic toxicities were not observed in these patients, and there was no treatment-related mortality. CONCLUSION: Decitabine combined with reduced FLAG regimen has a definite clinical efficacy in the treatment of senile patients with high-risk AML. This regimen, as induction remission regimen, can effectively improve the CR rate and reduce the adverse reactions. Therefore, it may be used as one of the preferred induction remission regimen to treat the senile patients with high-risk AML.

Case Report of Anti-CD123 Chimeric Antigen Receptor T-Cell Therapy Followed by Radiotherapy for a Recurrence of Blastic Plasmacytoid Dendritic Cell Neoplasm After Allogeneic Hematopoietic Stem Cell Transplantation.

BACKGROUND: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematopoietic malignancy. There is no standard chemotherapy regimen for BPDCN, and even allogeneic hematopoietic stem cell transplantation (allo-HSCT) has not been able to extend the survival of patients with BPDCN. CASE REPORT: Here, we present a case of recurrence of BPDCN in a patient with new nodules in his head six months after allo-HSCT. He was enrolled in a clinical trial of anti-CD123 chimeric antigen receptor (CAR) T-cell therapy (ChiCTR1900022058). However, there were no significant changes in the nodules 28 days after anti-CD123-CAR T-cell infusion. He received radiotherapy for the nodules when the proportion of anti-CD123-CAR T-cells in the peripheral blood was 2.8% and the adverse events related to the anti-CD123-CAR T-cell therapy were resolved. The proportion of anti-CD123-CAR T-cells, the level of CD123-CAR gene desoxyribonucleic acid, and the serum levels of cytokines in the patient's peripheral blood reached the highest peak 14 days after radiotherapy. Fortunately, the nodules disappeared gradually 28 days after radiotherapy. He achieved complete remission again from the anti-CD123-CAR T-cell therapy followed by radiotherapy. To date, he has maintained progression-free survival with complete donor chimerism for six months after the combination therapy. CONCLUSION: Anti-CD123-CAR T-cell therapy followed by radiotherapy for a recurrence of blastic plasmacytoid dendritic cell neoplasm after allo-HSCT is effective.