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:Infectious Complications of Targeted Therapies in Children with Leukemias and Lymphomas.
Infectious Complications of Targeted Therapies in Children with Leukemias and Lymphomas.
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本文综述儿童白血病和淋巴瘤靶向治疗药物的免疫抑制机制,并汇总医学文献中报道的感染并发症。利妥昔单抗通常不会增加3级感染风险,晚期非霍奇金淋巴瘤患者除外。吉妥珠单抗奥唑米星相关3级感染率较高,但与历史队列相当。帕博利珠单抗在严重感染方面的安全性较好。尽管blinatumomab治疗常出现低丙种球蛋白血症(HGG),但观察到的3级感染率较低,尤其是在复发性B细胞急性淋巴细胞白血病再诱导治疗后。伊马替尼和尼洛替尼通常不引起严重感染并发症,而达沙替尼可能略微增加机会性感染风险。克唑替尼以及泛Trk抑制剂entrectinib和larotrectinib的数据有限。tisagenlecleucel CAR-T 细胞治疗与儿童3级感染相关,并伴有HGG和免疫相关不良事件。超说明书使用的奥英妥珠单抗奥唑米星、维布妥昔单抗和维奈克拉相关3级治疗感染率较低;在T细胞恶性肿瘤标准化疗中加入硼替佐米,似乎可降低诱导期感染风险。本文还讨论各靶向药物对应的预防措施、免疫重建和疫苗接种,并与成人研究进行比较。
The aim of this review is to highlight mechanisms of immunosuppression for each agent, along with pooled analyses of infectious complications from the available medical literature. Rituximab confers no increase in grade 3 infectious risks, except in the case of patients with advanced-stage non-Hodgkin lymphoma. Gemtuzumab ozogamicin links with high rates of grade 3 infections which, however, are comparable with historical cohorts. Pembrolizumab exhibits a favorable safety profile in terms of severe infections. Despite high rates of hypogammaglobulinemia (HGG) with blinatumomab, low-grade 3 infection rates were observed, especially in the post-reinduction therapy of relapsed B-acute lymphoblastic leukemia.
Imatinib and nilotinib are generally devoid of severe infectious complications, but dasatinib may slightly increase the risk of opportunistic infections. Data on crizotinib and pan-Trk inhibitors entrectinib and larotrectinib are limited. CAR T-cell therapy with tisagenlecleucel is associated with grade 3 infections in children and is linked with HGG and the emergence of immune-related adverse events.
Off-label therapies inotuzumab ozogamicin, brentuximab vedotin, and venetoclax demonstrate low rates of treatment-related grade 3 infections, while the addition of bortezomib to standard chemotherapy in T-cell malignancies seems to decrease the infection risk during induction. Prophylaxis, immune reconstitution, and vaccinations for each targeted agent are discussed, along with comparisons to adult studies.
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