Toxicity and management in chimeric antigen receptor T-cell therapy / 临床儿科杂志

T cells can be genetically modified to target tumors through the expression of a chimeric antigen receptor (CAR). Most notably, CAR T cells have demonstrated its clinical efficacy in hematologic malignancies with evident responses when targeting solid tumors. However, CAR T cells therapy also has the capacity to elicit expected and unexpected toxicities including cytokine release syndrome, neurologic toxicity, on target/off tumor recognition, and anaphylaxis. Theoretical toxicities include clonal expansion secondary to insertional oncogenesis, graft versus host disease, and off-target antigen recognition. Abrogating toxicity has become a critical step in the successful application of this emerging technology. To this end, we review the reported and theoretical toxicities of CAR T cells therapy and strategies to cope with it.

Inlfuence of transport protein gene polymorphisms on the effects and toxicity of high-dose methotrexate in child-hood acute lymphoblastic leukemia / 临床儿科杂志

Objectives To investigate the inlfuence of polymorphisms of SLC19A1 80G>A, MDR1 exon26C>T and MDR1 exon21G>T/A on curative effect and adverse reaction of high-dose methotrexate in patients with acute lymphoblastic leukemia. Methods MALDI-TOF-MS technique was used to detect the polymorphisms of SLC19A1 80G>A, MDR1 exon 26C>T and MDR1 exon21G>T/A in 108 patients with acute lymphoblastic leukemia (ALL). The relationship of genetic polymorphism, survival rate and toxicity was analyzed. Results The 36-month event-free survival was not related to any polymorphisms of MDR1 and SLC19A1. Patients with mutant types of MDR1 exon26C>T and MDR1 exon21G>T/A showed a much higher MTX plasma levels at 24 hours and higher incidence of hepatic injury (PT, MDR1 exon21G>T/A has a large inlfuence on hepatic toxicity and plasma concentra-tions of MTX.