经过嵌合抗原受体（CAR）T细胞疗法后，持续的细胞减少是一个重要的临床问题，其潜在的病理生理机制仍不明确。本研究旨在探讨（CAR）T细胞扩增动态和血清蛋白组学如何影响CD19定向的CAR-T细胞疗法后的中性粒细胞恢复表型。与“快速”或“再生障碍”恢复相比，存活结果有利于出现“间歇性”中性粒细胞恢复（例如反复出现中性粒细胞下降）的患者。间歇性患者显示出CAR-T细胞扩增增加，再生障碍患者则表现出扩增和肿瘤负荷之间不利的关系。对CAR-T疗法后首个月基线和患者血清的蛋白组学分析显示，再生障碍表型组中存在更高水平的内皮功能障碍标志物、炎症细胞因子、巨噬细胞活化和T细胞抑制。因此，持续的中性粒细胞再生障碍发生在术前存在全身免疫失调的患者中，随后CAR-T扩增和髓系相关炎症变化受到影响。中性粒细胞恢复与生存结果之间的关联凸显了寄主造血作用与CAR-T输注所激发的免疫状态之间的重要相互作用。

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.