IntroductionHematologic toxicity (HT) is a joint adverse event after CAR-T cells infusion. Some patients experience prolonged hematologic toxicity (PHT), which is challenging to treat.MethodsWe collected clinical data from patients with relapsed refractory B-ALL treated with CD19 CAR-T cells. Patients with PHT who did not respond to erythropoietin, platelet receptor agonists, transfusion, or G-CSF and eventually received low-dose prednisone therapy were included in the analysis. We retrospectively analyzed the efficacy and safety of low-dose prednisone on PHT.ResultsAmong 109 patients treated with CD19 CAR-T cells, 78.9% (86/109) of patients were evaluated as PHT. Of these, 15 patients had persistent hematological toxicity after infusion (12 were grade 3/4 cytopenia, 12 were trilineage cytopenia and 3 were bilineage cytopenia), 2 developed cytopenia without apparent cause after D28. The initial prednisone dose was 0.5 mg/kg/day, and the median response time was 21 days (7-40 days). The recovery rate of blood count was 100%, and the complete recovery rate ranged from 60% to 66.67%. Especially exciting was that HT recurred in 6 patients after stopping prednisone. They were relieved again after the administration of prednisone. The median follow-up time was 14.97 months (4.1-31.2 months). Twelve-month duration of PFS and OS rates were 58.8% (±11.9%) and 64.7% (±11.6%). We did not observe any other side effects of prednisone apart from drug-controllable hyperglycemia and hypertension.DiscussionWe suggest that low-dose prednisone is a beneficial and tolerable therapy for PHT after CAR-T cells. The trials have been registered at www.chictr.org.cn as ChiCTR-ONN-16009862 (November 14, 2016) and ChiCTR1800015164 (March 11, 2018).

With the gradual improvement of treatment regimens, the survival time of multiple myeloma (MM) patients has been significantly prolonged. Even so, MM is still a nightmare with an inferior prognosis. B-cell maturation antigen (BCMA) is highly expressed on the surface of malignant myeloma cells. For the past few years, significant progress has been made in various BCMA-targeted immunotherapies for treating patients with RRMM, including anti-BCMA mAbs, antibody-drug conjugates, bispecific T-cell engagers, and BCMA-targeted adoptive cell therapy like chimeric antigen receptor (CAR)-T cell. The 63rd annual meeting of the American Society of Hematology updated some information about the application of BCMA in MM. This review summarizes part of the related points presented at this conference.

The intestine is critically crucial for nutrient absorption and host defense against exogenous stimuli. Inflammation-related intestinal diseases, including enteritis, inflammatory bowel disease (IBD), and colorectal cancer (CRC), are heavy burdens for human beings due to their high incidence and devastating clinical symptoms. Current studies have confirmed that inflammatory responses, along with oxidative stress and dysbiosis as critical pathogenesis, are involved in most intestinal diseases. Polyphenols are secondary metabolites derived from plants, which possess convincible anti-oxidative and anti-inflammatory properties, as well as regulation of intestinal microbiome, indicating the potential applications in enterocolitis and CRC. Actually, accumulating studies based on the biological functions of polyphenols have been performed to investigate the functional roles and underlying mechanisms over the last few decades. Based on the mounting evidence of literature, the objective of this review is to outline the current research progress regarding the category, biological functions, and metabolism of polyphenols within the intestine, as well as applications for the prevention and treatment of intestinal diseases, which might provide ever-expanding new insights for the utilization of natural polyphenols.

Opinion statementAlthough chimeric antigen receptor T cell immunotherapy has been successfully applied in patients with hematological malignancies, several obstacles still need to be overcome, such as high relapse rates and side effects. Overcoming the limitations of CAR-T cell therapy and boosting the efficacy of CAR-T cell therapy are urgent issues that must be addressed. The exploration of small-molecule compounds in combination with CAR-T cell therapies has achieved promising success in pre-clinical and clinical studies in recent years. Protein kinase inhibitors, demethylating drugs, HDAC inhibitors, PI3K inhibitors, immunomodulatory drugs, Akt inhibitors, mTOR inhibitors, and Bcl-2 inhibitors exhibited potential synergy in combination with CAR-T cell therapy. In this review, we will discuss the recent application of these combination therapies for improved outcomes of CAR-T cell therapy.