Citations

Abstract Chimeric antigen receptor (CAR) T-cell therapy has emerged as a transformative treatment for hematological malignancies, yet its potential to drive lymphomagenesis poses significant clinical concerns. In this study, we investigated the mechanisms underlying CAR T-cell–associated lymphomagenesis in the gastrointestinal (GI) tract on a single case, focusing specifically on the role of integrin α4β7 expression and a predisposing somatic SH2B3 mutation. We observed oligoclonal CAR T cells homing to, and clonally expanding in, the GI tract, with the dominant expanded clone harboring both a pathogenic SH2B3 mutation and a CAR transgene integration within a TFCP2 locus. The clonal CAR T cells subsequently transitioned beyond the GI tract into the peripheral blood, suggesting a potential pathway for systemic dissemination. We found clinical, histological, and molecular evidence demonstrating the efficacy of cyclosporine in reducing the expanded malignant clone and achieving durable clinical remission for more than a year. Our findings highlight the complex interplay between CAR T-cell therapy, preexisting genetic vulnerabilities, and the GI microenvironment, emphasizing the need for vigilant monitoring and tailored therapeutic strategies to address the risks associated with CAR T-cell lymphomagenesis.

Summary: Most unstable metacarpal and phalangeal fractures for which operative treatment is indicated can be reduced and stabilized with either open or closed techniques using local anesthetic with epinephrine instead of intravenous sedation or general anesthesia. With the patient wide-awake during surgery, the hand can be taken through active range of motion to assess fracture stability. In this article, the authors review the rationale and technique for wide-awake, local anesthesia, no tourniquet surgery in the treatment of phalangeal and metacarpal fractures and impart pearls to optimize the patient experience and illustrate common fixation techniques using percutaneous Kirschner wires. The intraoperative assessment of fracture stability permits an accelerated, protected–range-of-motion protocol that minimizes postoperative stiffness and facilitates expedient recovery.