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| Item Type: | Article |
|---|---|
| Title: | Severe hematotoxicity after CD19 CAR-T therapy is associated with suppressive immune dysregulation and limited CAR-T expansion |
| Creators Name: | Rejeski, K. and Perez, A. and Iacoboni, G. and Blumenberg, V. and Bücklein, V.L. and Völkl, S. and Penack, O. and Albanyan, O. and Stock, S. and Müller, F. and Karschnia, P. and Petrera, A. and Reid, K. and Faramand, R. and Davila, M.L. and Modi, K. and Dean, E.A. and Bachmeier, C. and von Bergwelt-Baildon, M. and Locke, F.L. and Bethge, W. and Bullinger, L. and Mackensen, A. and Barba, P. and Jain, M.D. and Subklewe, M. |
| Abstract: | Prolonged cytopenias after chimeric antigen receptor (CAR) T cell therapy are a significant clinical problem and the underlying pathophysiology remains poorly understood. Here, we investigated how (CAR) T cell expansion dynamics and serum proteomics affect neutrophil recovery phenotypes after CD19-directed CAR T cell therapy. Survival favored patients with "intermittent" neutrophil recovery (e.g., recurrent neutrophil dips) compared to either "quick" or "aplastic" recovery. While intermittent patients displayed increased CAR T cell expansion, aplastic patients exhibited an unfavorable relationship between expansion and tumor burden. Proteomics of patient serum collected at baseline and in the first month after CAR-T therapy revealed higher markers of endothelial dysfunction, inflammatory cytokines, macrophage activation, and T cell suppression in the aplastic phenotype group. Prolonged neutrophil aplasia thus occurs in patients with systemic immune dysregulation at baseline with subsequently impaired CAR-T expansion and myeloid-related inflammatory changes. The association between neutrophil recovery and survival outcomes highlights critical interactions between host hematopoiesis and the immune state stimulated by CAR-T infusion. |
| Keywords: | Signal Transducing Adaptor Proteins, CD19 Antigen, Cell Cycle, Adoptive Immunotherapy, Chimeric Antigen Receptors |
| Source: | Science Advances |
| ISSN: | 2375-2548 |
| Publisher: | American Association for the Advancement of Science |
| Volume: | 9 |
| Number: | 38 |
| Page Range: | eadg3919 |
| Date: | 22 September 2023 |
| Official Publication: | https://doi.org/10.1126/sciadv.adg3919 |
| PubMed: | View item in PubMed |
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