CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Abnormal bone marrow findings in patients following treatment with chimeric antigen receptor-T cell therapy.
Abnormal bone marrow findings in patients following treatment with chimeric antigen receptor-T cell therapy.
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这些数据代表了在接受 CAR-T 细胞免疫治疗的患者中,对 BM 变化进行的首次系统性观察。
CAR-T 细胞免疫治疗输注后,骨髓(BM)评估并非常规用于监测血细胞减少、噬血细胞性淋巴组织细胞增生症或感染等不良事件。我们机构已将BM活检作为CAR-T 细胞治疗方案的一部分,涵盖治疗前、治疗后时间点以及长期随访期间。
我们对259例患者接受CAR-T 细胞免疫治疗后样本中观察到的BM异常进行了系统性回顾性分析。我们将BM病理学发现与死亡率、复发/残留病灶及实验室检查值进行了相关性分析。
在CAR-T 输注后中位35.5天时,25.5%的患者出现严重骨髓细胞减少,6.2%出现浆液性萎缩,外周血细胞减少也证实了这些观察结果。与CAR-T 输注后疾病负荷降低相关的骨髓特征包括16例患者中观察到的淋巴细胞增多,以及25例患者中观察到的巨噬细胞增多或肉芽肿性反应。然而,一项100天里程碑分析还显示,骨髓组织细胞增多与较低的生存率相关(中位OS 6.0 vs. 21.4个月,p = .026),2-3级骨髓网状纤维化(18例患者)也是如此(中位OS 12.5 vs. 24.2个月,p = .034)。
Bone marrow (BM) assessment after CAR-T cell immunotherapy infusion is not routinely performed to monitor adverse events such as cytopenias, hemophagocytic lymphohistiocytosis, or infections. Our institution has performed BM biopsies as part of CAR-T cell treatment protocols, encompassing pre- and post-treatment time points and during long-term follow-up.
We conducted a systematic retrospective review of BM abnormalities observed in samples from 259 patients following CAR-T cell immunotherapy. We correlated BM pathology findings with mortality, relapse/residual disease, and laboratory values.
At a median of 35.5 days post-CAR-T infusion, 25.5% showed severe marrow hypocellularity, and 6.2% showed serous atrophy, and peripheral blood cytopenias corroborated these observations. Marrow features associated with reduced disease burden post-CAR-T infusion include increased lymphocytes seen in 16 patients and an increase of macrophages or granulomatous response seen in 25 patients. However, a 100-day landmark analysis also showed increased marrow histiocytes were associated with lower survival (median OS 6.0 vs. 21.4 months, p = .026), as was grade 2-3 marrow reticulin (18 patients) (median OS 12.5 vs. 24.2 months, p = .034).
These data represent the first systematic observations of BM changes in patients receiving CAR-T cell immunotherapy.
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