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:High-grade B-cell lymphoma, not otherwise specified: CNS involvement and outcomes in a multi-institutional series.
11例患者(7%)在诊断时存在基线CNS受累(软脑膜=6,实质=4,两者均有=1)。
关于高级别B细胞淋巴瘤,非特指型(HGBL NOS)的中枢神经系统(CNS)风险知之甚少。因此,我们试图描述HGBL NOS中基线CNS受累率、初次治疗后的CNS复发风险以及管理策略。在这项多中心回顾性研究中,我们纳入了2016年至2021年间在美国20家机构接受治疗的160例新诊断HGBL NOS成人患者。11例患者(7%)在诊断时存在基线CNS受累(软脑膜=6,实质=4,两者均有=1)。基线CNS受累仅与MYC重排(OR=3.5)以及睾丸(男性)或女性盆腔(女性)受累(OR=8.1)显著相关。伴有基线CNS受累(中位PFS=4年)与不伴有基线CNS受累(中位PFS=2.4年)的HGBL NOS患者之间,生存结局无显著差异(P=0.45)。3年时CNS复发的累积发生率为11%。伴有基线CNS受累的患者风险最高(48.5% vs 不伴有基线CNS受累者为8%),因此被排除在CNS复发危险因素分析之外。CNS复发风险与血液或骨髓受累、CD5表达、非生发中心B细胞亚型以及“双表达淋巴瘤”表型显著相关,然而高CNS IPI则不相关。复发性HGBL NOS的预后较差,无论复发是全身性还是局限于CNS,并且采用目前可用的挽救策略,包括自体移植和CAR-T 细胞模式,几乎所有CNS复发患者最终都死于该疾病。
Little is known about the central nervous system (CNS) risk in high-grade B-cell lymphoma, not otherwise specified (HGBL NOS). Hence, we sought to describe the rates of baseline CNS involvement, risk of CNS recurrence after primary therapy, and management strategies in HGBL NOS. In this multicenter retrospective study, we included 160 adults with newly diagnosed HGBL NOS treated between 2016 and 2021 at 20 US institutions. Eleven patients (7%) had baseline CNS involvement at diagnosis (leptomeningeal = 6, parenchymal = 4, and both = 1). Baseline CNS involvement was significantly associated only with MYC rearrangement (OR = 3.5) and testicular (in men) or female pelvic (in women) involvement (OR = 8.1). There was no significant difference in survival outcomes between patients with HGBL NOS with (median PFS = 4 years) or without (median PFS = 2.4 years) baseline CNS involvement (P = 0.45). The cumulative incidence of CNS recurrence at 3 years was 11%. Patients with baseline CNS involvement were at the highest risk (48.5% vs 8% for those without baseline CNS involvement) and were excluded from the risk factors analysis for CNS recurrence. The risk for CNS recurrence was significantly associated with blood or bone marrow involvement, CD5 expression, non-germinal center B-cell subtype, and "dual-expresser lymphoma" phenotype, however, high CNS IPI was not. The prognosis of relapsed HGBL NOS was poor, regardless of whether recurrence was systemic or limited to the CNS, and with currently available salvage strategies, including autologous transplantation and chimeric antigen receptor T-cell modalities, almost all patients with CNS recurrence ultimately succumbed to their disease.
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