CAR transgenic T-cell lymphoproliferative neoplasm (CTTLN): malignant transformation of cellular immunotherapy

Engineered T-cells have transformed hematooncology, but CAR transgene-bearing T-cell malignancies have emerged as a rare and serious genomic safety signal after CAR-T therapy. Available data support a multistep model in which pre-existing clonal fitness, CAR-T manufacture, vector integration, construct biology and post-infusion selection may contribute to different degrees. We review reported cases of CAR-transgenic T-cell lymphoproliferative neoplasms (CTTLN) and propose practical diagnostic criteria with a proportionate approach to genomic surveillance.