决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
英文原题:Pre-CAR-HEMATOTOX at Leukapheresis Predicts Delayed Platelet Recovery After Idecabtagene Vicleucel in Multiple Myeloma.
Pre-CAR-HEMATOTOX at Leukapheresis Predicts Delayed Platelet Recovery After Idecabtagene Vicleucel in Multiple Myeloma.
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在白细胞分离术时评估的 Pre-CAR-HEMATOTOX 可预测 ide-cel 后血小板恢复延迟,并可能支持 BT 选择前的早期风险分层。
CAR-HEMATOTOX评分与CAR-T 细胞治疗后的血液学毒性相关,但该评分通常在淋巴细胞清除治疗前不久评估,此时造血储备可能已受桥接治疗影响。我们研究了在白细胞单采时、开始桥接治疗前评估的CAR-HEMATOTOX评分(Pre-CAR-HEMATOTOX),能否预测复发/难治性多发性骨髓瘤患者接受idecabtagene vicleucel(ide-cel)后的血小板延迟恢复。
我们开展了一项单中心回顾性队列研究,纳入2022年11月至2026年3月期间接受白细胞单采并随后接受ide-cel治疗的连续复发/难治性多发性骨髓瘤患者。主要终点为血小板恢复至≥100×10⁹/L所需时间,且期间无需输注血小板或接受血小板生成素受体激动剂支持。次要终点包括血小板恢复至≥75×10⁹/L所需时间、在无需粒细胞集落刺激因子支持下中性粒细胞恢复至≥1.0×10⁹/L所需时间,以及血小板输注负担。
在96例患者中,Pre-CAR-HEMATOTOX低分组的血小板恢复至≥100×10⁹/L的中位时间显著短于高分组(1.8个月比15.8个月,P<.001)。恢复至≥75×10⁹/L的结果相似(1.3个月比6.3个月,P=.005)。在主要和探索性多变量模型中,高Pre-CAR-HEMATOTOX评分均与血小板延迟恢复独立相关。高评分也与更大的血小板输注负担相关。相比之下,与中性粒细胞延迟恢复独立相关的是强化桥接治疗(BT),而非Pre-CAR-HEMATOTOX评分。
在白细胞单采时评估的Pre-CAR-HEMATOTOX可预测ide-cel治疗后血小板延迟恢复,有望在选择桥接治疗前用于早期风险分层。
The CAR-HEMATOTOX score has been associated with hematologic toxicity after chimeric antigen receptor T-cell therapy, but it is usually assessed shortly before lymphodepletion, when hematopoietic reserve may already be affected by bridging therapy. We investigated whether the CAR-HEMATOTOX score assessed at leukapheresis, before bridging therapy initiation (Pre-CAR-HEMATOTOX), could predict delayed platelet recovery after idecabtagene vicleucel (ide-cel) in relapsed/refractory multiple myeloma.
We conducted a single-center retrospective cohort study of consecutive patients with relapsed/refractory multiple myeloma who underwent leukapheresis and subsequently received ide-cel between November 2022 and March 2026. The primary endpoint was time to platelet recovery to ≥ 100 × 10 9 /L without platelet transfusion or thrombopoietin receptor agonist support. Secondary endpoints included time to platelet recovery to ≥ 75 × 10 9 /L, time to neutrophil recovery to ≥ 1.0 × 10 9 /L without granulocyte colony-stimulating factor support, and platelet transfusion burden.
Among 96 patients, median time to platelet recovery to ≥ 100 × 10 9 /L was significantly shorter in the Pre-CAR-HEMATOTOX low group than in the high group (1.8 vs. 15.8 months, P < .001). Similar findings were observed for recovery to ≥ 75 × 10 9 /L (1.3 vs. 6.3 months, P = .005). High Pre-CAR-HEMATOTOX remained independently associated with delayed platelet recovery in both the primary and exploratory multivariable models. High Pre-CAR-HEMATOTOX was also associated with greater platelet transfusion burden. In contrast, intensive BT, rather than Pre-CAR-HEMATOTOX, was independently associated with delayed neutrophil recovery.
Pre-CAR-HEMATOTOX assessed at leukapheresis predicted delayed platelet recovery after ide-cel and may support early risk stratification before BT selection.
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