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.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Patterns of immune recovery after axicabtagene ciloleucel for aggressive B-cell lymphoma.
CD8+ T细胞和NK细胞的中位数在输注后2个月内分别增加至>300/mm³和>100/mm³。
抗CD19CAR-T 细胞治疗后的血液毒性因其潜在长期影响而受到关注,然而,B细胞再生障碍之外的淋巴细胞亚群和免疫球蛋白水平的恢复情况仍知之甚少。我们回顾性分析了2020年至2024年间连续76例接受axicabtagene ciloleucel(axi-cel)治疗的复发/难治性侵袭性B细胞淋巴瘤患者,重点关注基本免疫恢复模式及其对结局的影响。输注后2个月内,CD8+ T细胞和NK细胞中位数分别增至>300/mm³和>100/mm³。CD4+ T细胞恢复较慢,12个月时>200/mm³细胞计数的累积发生率为42%。12个月时18%可检测到B细胞。免疫球蛋白水平最初下降后趋于平稳,12个月时免疫球蛋白G(IgG)水平>400 mg/dL的发生率为51%。改良EASIX>2.00与CD3+ T细胞、CD4+ T细胞和CD8+ T细胞动力学延迟相关,地塞米松累积剂量>120 mg与CD4+ T细胞、NK细胞和IgG恢复延迟相关。输注后1个月时,低CD4+ T细胞计数和高CAR-HEMATOTOX分别预测较差的12个月无进展生存期(风险比[HR] 2.81和3.34)和总生存期(HR 3.21和4.41)。axi-cel治疗后,CD4+ T细胞和IgG在第一年内恢复缓慢,而CD8+ T细胞和NK细胞快速增加。较高的改良EASIX评分可能预测较慢的细胞恢复,而皮质类固醇可能延迟细胞和体液恢复。较低的CD4+ T细胞计数与较差的结局相关。
Hematotoxicity after anti-CD19 chimeric antigen receptor T-cell therapy has drawn attention for potential long-term effects, and yet, recovery of lymphocyte subsets and immunoglobulin levels beyond B-cell aplasia remains poorly understood. We retrospectively analyzed 76 consecutive axicabtagene ciloleucel (axi-cel) recipients with relapsed/refractory aggressive B-cell lymphoma between 2020 and 2024, focusing on basic immune recovery patterns and their impact on outcomes. Median CD8 + T and NK cells increased to >300/mm 3 and >100/mm 3 , respectively, within 2 months after infusion. CD4 + T-cell recovery was slower, with 42% cumulative incidence of >200/mm 3 cell count at 12 months. B-cells were detectable in 18% at 12 months. Immunoglobulin levels initially declined and then plateaued, with 51% incidence of immunoglobulin G (IgG) levels > 400 mg/dL at 12 months. Modified EASIX > 2.00 was associated with delayed kinetics of CD3 + T-cells, CD4 + T-cells, and CD8 + T-cells, and cumulative dexamethasone dose > 120 mg with delayed recovery of CD4 + T-cells, NK cells, and IgG. At 1 month post-infusion, low CD4 + T-cell count and high CAR-HEMATOTOX predicted worse 12-month progression-free survival (hazard ratio [HR] 2.81 and 3.34) and overall survival (HR 3.21 and 4.41), respectively. After axi-cel, CD4 + T-cells and IgG recovered slowly during the first year, while CD8 + T and NK cells increased rapidly. A higher modified EASIX score may predict slower cellular recovery, while corticosteroids may delay both cellular and humoral recovery. Lower CD4 + T-cell count was associated with worse outcomes.
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