Adverse events following infusion of T cells for adoptive immunotherapy: a 10-year experience
Adverse events following infusion of T cells for adoptive immunotherapy: a 10-year experience
复制标题
DOI：
10.3109/14653241003709686
复制
发表时间：
2010-10-01
期刊：
影响因子：
4.5
通讯作者：
Heslop, Helen E.
中科院分区：
文献类型：
--
作者：
Cruz, Conrad Russell;Hanley, Patrick J.;Heslop, Helen E.
背景目标。美国食品和药物管理局（FDA）目前建议在T细胞输注后至少进行4小时的受者监测，以检测早期输注反应。最近的灾难性反应的“首次在人”的生物制剂强调了这一规则的重要性，为初步研究的新产品。这种监测对较好建立的代理人的价值不太明显。方法.我们回顾了本中心新药（IND）研究中给予体外扩增T细胞产品（抗原特异性细胞毒性T淋巴细胞、同种异体耗竭T细胞和遗传修饰T细胞）后的输注相关不良事件（AE）。结果从1998年到2008年，我们向180名接受者输注了381种T细胞产品，这些接受者参加了18项研究，接受了针对恶性肿瘤或移植后病毒感染的T细胞。在初始监测或24小时随访期间，未发生3-4级输注反应。在21次输注期间或输注后立即（最长6小时）发生了24起轻度（1-2级）AE，最常见的是恶心和呕吐（10/24，41.6%），可能是由于二甲基亚砜冷冻保护剂，以及低血压（20.8%），可归因于苯海拉明术前用药。在输注后24小时内报告了22起额外的非重度事件，最常见的是培养阴性发热、寒战和恶心。不良事件风险增加与年龄相关[发生率比（IRR）0.98; 95%置信区间（CI）0.96-1.00，P = 0.05]，而报告过敏的患者中即刻输注相关事件风险增加更高（IRR 2.72，95% CI 1.00-7.40，P = 0.05）;性别、疾病类型和T细胞来源（同种异体或自体）对不良事件的频率没有影响。结论.这些T细胞产品的输注在门诊环境中是安全的，并且没有严重的反应，因此输注后1小时的监测可能就足够了。由于许多AE可归因于苯海拉明术前用药，因此应选择较低剂量（0.25 mg/kg）。
Background aims. The Food and Drug Administration (FDA) currently recommends at least 4 h of recipient monitoring after T cell infusions to detect early infusion reactions. Recent catastrophic reactions to 'first-in-man' biologic agents have emphasized the importance of this rule for initial studies of new products. The value of such monitoring for better established agents is less obvious. Methods. We reviewed infusion-related adverse events (AE) following administration of ex vivo-expanded T cell products (antigen-specific cytotoxic T lymphocytes, allodepleted T cells, and genetically modified T cells) on investigational new drug (IND) studies in our center. Results. From 1998 to 2008, we infused 381 T cell products to 180 recipients, enrolled on 18 studies, receiving T cells targeting malignancies or post-transplant viral infections. There were no grade 3-4 infusion reactions during initial monitoring or 24-h follow-up. Twenty-four mild (grade 1-2) AE occurred in 21 infusions either during or immediately following infusion (up to 6 h), most commonly nausea and vomiting (10/24, 41.6%), probably because of the dimethyl sulfoxide cryoprotectant, and hypotension (20.8%), attributable to diphenhydramine pre-medication. Twenty-two additional non-severe events were reported within 24 h of infusion, most commonly culture-negative fever, chills and nausea. An increased risk of adverse events was associated with age [incidence rate ratio (IRR) 0.98; 95% confidence interval (CI) 0.96-1.00, P = 0.05], while an increased risk of immediate infusion-related events was higher in patients reporting allergies (IRR 2.72, 95% CI 1.00-7.40, P = 0.05); sex, disease type and T cell source (allogeneic or autologous) had no effect on frequency of adverse events. Conclusions. Infusion of these T cell products was safe in the outpatient setting and associated with no severe reactions, so monitoring for 1 h after infusion is probably sufficient. As many of the AE were attributable to diphenhydramine premedication, a lower dose (0.25 mg/kg) should be selected.