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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., Perez, A., Iacoboni, G., Blumenberg, V., Bücklein, V.L., Völkl, S., Penack, O., Albanyan, O., Stock, S., Müller, F., Karschnia, P., Petrera, A., Reid, K., Faramand, R., Davila, M.L., Modi, K., Dean, E.A., Bachmeier, C., von Bergwelt-Baildon, M., Locke, F.L., Bethge, W., Bullinger, L., Mackensen, A., Barba, P., 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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