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:Atypical lymphoid proliferations associated with therapeutic intervention: a report of the 2024 EA4HP/SH lymphoma workshop.
Atypical lymphoid proliferations associated with therapeutic intervention: a report of the 2024 EA4HP/SH lymphoma workshop.
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2024 年欧洲血液病理学协会/血液病理学会在克罗地亚杜布罗夫尼克举办的研讨会上,讨论了肿瘤性与反应性淋巴增殖之间难以判定的界限。第 3 场聚焦治疗干预相关的非典型淋巴样增殖。提交的 44 个病例代表了多种治疗情境下的淋巴增殖性疾病(LPD),包括免疫抑制和免疫调节治疗、实体瘤的各类治疗、伴嗜酸性粒细胞增多和全身症状的药物反应(DRESS)、B 细胞淋巴瘤 CAR-T 治疗、用于 SLL/CLL 的布鲁顿酪氨酸激酶抑制剂(BTKI)、ABL 激酶抑制剂 dasatinib,以及 COVID-19 疫苗接种。病例强调,充分掌握临床资料(包括用药史和疾病分布)对于作出可靠诊断至关重要。
免疫抑制或免疫调节治疗相关 LPD 中,最具诊断挑战的是 T 细胞和 NK 细胞来源浸润,因为其克隆性从无到有不等。DRESS 相关淋巴结肿大呈现多种组织学模式,其中最难鉴别的是 T 细胞淋巴瘤。B 细胞肿瘤接受 CAR-T 后观察到的 LPD 表型出乎预期,可能源于谱系转换/转分化,或采集的 T 细胞本身已携带癌症相关变异。因手术暂时中断 CLL/SLL 的 BTKI 治疗可导致“假性 Richter 转化”,重新开始治疗后病变消退。Dasatinib 可引起具有特殊旺盛滤泡增生的淋巴结肿大,停药后消退。少数经过深入研究的 COVID-19 疫苗相关淋巴结肿大病例显示免疫应答紊乱。本报告描述了诊断这些疑难病例时最重要的特征。
The challenging boundaries between neoplastic and reactive lymphoproliferations were discussed during the 2024 European Association for Haematopathology/Society for Hematopathology workshop in Dubrovnik, Croatia. Session 3 focussed on the atypical lymphoid proliferations associated with therapeutic interventions. Forty-four cases were submitted representing a broad spectrum of lymphoproliferative disorders (LPDs) encountered in the settings of immunosuppressive and immunomodulatory therapies, various interventions for solid tumor treatment, drug reaction with eosinophilia and systemic symptoms (DRESS), CAR T-cell therapy for B-cell lymphomas, Bruton tyrosine kinase inhibitors (BTKI) for SLL/CLL treatment, ABL-kinase inhibitor dasatinib, and COVID-19 vaccination. The cases of this session highlighted the importance of having sufficient clinical information including drug history and distribution of disease in order to achieve reliable diagnosis.
Among LPDs associated with immunosuppressive and immunomodulatory therapies, the most challenging were T- and NK-derived infiltrates as they ranged from non-clonal to clonal. DRESS-associated lymphadenopathy exhibited variable histologic patterns with the most difficult differential diagnosis being with a T-cell lymphoma. LPDs observed after CAR T-cell therapy for B-cell neoplasms exhibited unexpected phenotypes resulting either from lineage switching/transdifferentiation, or from harvested T-cells already harbouring cancer-associated variants.
Temporary interruption of BTKI treatment for CLL/SLL due to surgical procedures led to a "Pseudo-Richter transformation" that disappeared after reintroduction of therapy. Dasatinib led to a lymphadenopathy with a peculiar florid follicular hyperplasia that regressed after discontinuation of therapy. The findings of the few thoroughly studied COVID-19 vaccination associated lymphadenopathy cases reflected a disordered immune response. This report describes the most important features for diagnosis of these challenging cases.
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