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<p>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.</p>

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A clonally expanded nodal T-cell population diagnosed as T-cell lymphoma after CAR-T therapy

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年8月12日

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  • 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

摘要

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.