A clonally expanded nodal T-cell population diagnosed as T-cell lymphoma after CAR-T therapy
- Katie Maurer
- Jackson A. Weir
- Adi Nagler
- Nicholas J. Haradhvala
- Hariharan Bharadwaj
- Jacob Shapiro
- Somkene Alakwe
- Vipin Kumar
- Brianna Waller
- Mikaela McDonough
- Jamie Dela Cruz
- Loida Luna
- Emma Lin
- Linsey Gong
- Qiyu Gong
- Mehdi Borji
- Phillip D. Michaels
- Jacob P. Laubach
- Geraldine Pinkus
- Gad Getz
- Catherine J. Wu
- Fei Chen
- Caron Jacobson
2025-08-12
Reports of secondary malignancies after chimeric antigen receptor (CAR)-T and possible CAR-T derived malignant transformation necessitate caution. Here we describe a patient with diffuse large B-cell lymphoma who developed new lymphadenopathy 2.5 years after CAR-T in the context of COVID-19 infection with histopathologic features consistent with T-cell lymphoma (TCL). Deep molecular interrogation with genomic sequencing and single-cell spatial transcriptomics reveals a highly proliferative clonal T-cell population co-expressing CD4 and CD8 with biallelic TCR rearrangement and no evidence of the CAR construct. The expanded clonotype displayed T follicular helper (TFH) cell transcriptomic programs and occupies immune-excluded spatial niches within the lymph node, supportive of TFH-like neoplastic T cell behavior. Remarkably, the lymphadenopathy spontaneously resolved on interval imaging. Our data underscore the need for better understanding of post-CAR-T clonal T-cell lymphoproliferative disorders to avoid unnecessary treatment and higher specificity in diagnostic methods for TCL.