<p>Bone marrow toxicity, or immune effector cell-associated hematotoxicity (ICAHT), is a notable complication of CAR T-cell therapy, characterized by persistent cytopenia’s and typically classified into three phenotypes: transient, intermittent and aplastic. This study aimed to characterize the bone marrow immune landscape associated with ICAHT phenotype( aplastic and intermittent) by analyzing patients with diffuse large B-cell lymphoma (DLBCL) treated with axicabtagene ciloleucel (axi-cel) who developed ICAHT, in comparison to healthy controls and between the two ICAHT subtypes. Bone marrow samples were profiled using mass cytometry (CyTOF) with a 41-antibody panel. Compared to healthy individuals, ICAHT patients showed increased frequencies of activated/effector T cells and reduced levels of B cells and CD34<sup>+</sup> early hematopoietic cells. Within the ICAHT cohort, patients with the aplastic phenotype exhibited significantly higher levels of CAR T cells, activated T cells, regulatory T cells (Tregs), Th1, and Th17 cells, along with a higher proportion of CD34<sup>+</sup> early hematopoietic cells. In contrast, the intermittent phenotype was characterized by a greater abundance of naïve T cells, Th2 cells, and myeloid lineage markers such as CD33, CD11b, and CD11c. In this small, exploratory analysis, distinct immunological patterns were observed between intermittent and aplastic ICAHT phenotypes, suggesting potentially different mechanisms of hematopoietic disruption after CAR T-cell therapy that require confirmation in larger studies.</p>

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Distinct cellular signatures in aplastic and intermittent phenotypes of immune effector cell-associated hematotoxicity

  • Ben Varon,
  • Amir Grau,
  • Noga Setter Marco,
  • Anwar Khatib,
  • Tsofia Levi,
  • Riva Fineman,
  • Inna Tzoran,
  • Nivin Mustafa,
  • Tsila Zuckerman,
  • Netanel A. Horowitz,
  • Noa Lavi,
  • Rostislav Novak,
  • Ofrat Beyar-Katz

摘要

Bone marrow toxicity, or immune effector cell-associated hematotoxicity (ICAHT), is a notable complication of CAR T-cell therapy, characterized by persistent cytopenia’s and typically classified into three phenotypes: transient, intermittent and aplastic. This study aimed to characterize the bone marrow immune landscape associated with ICAHT phenotype( aplastic and intermittent) by analyzing patients with diffuse large B-cell lymphoma (DLBCL) treated with axicabtagene ciloleucel (axi-cel) who developed ICAHT, in comparison to healthy controls and between the two ICAHT subtypes. Bone marrow samples were profiled using mass cytometry (CyTOF) with a 41-antibody panel. Compared to healthy individuals, ICAHT patients showed increased frequencies of activated/effector T cells and reduced levels of B cells and CD34+ early hematopoietic cells. Within the ICAHT cohort, patients with the aplastic phenotype exhibited significantly higher levels of CAR T cells, activated T cells, regulatory T cells (Tregs), Th1, and Th17 cells, along with a higher proportion of CD34+ early hematopoietic cells. In contrast, the intermittent phenotype was characterized by a greater abundance of naïve T cells, Th2 cells, and myeloid lineage markers such as CD33, CD11b, and CD11c. In this small, exploratory analysis, distinct immunological patterns were observed between intermittent and aplastic ICAHT phenotypes, suggesting potentially different mechanisms of hematopoietic disruption after CAR T-cell therapy that require confirmation in larger studies.