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:Retrospective Analysis of Incidence and Etiology of Severe Infections in Children Receiving Therapy for High-Risk Neuroblastoma: A Large Single-Center Experience.
尽管感染相关死亡率较低,但严重感染仍是 HR-NB 治疗中常见且具有重要临床意义的并发症。在未采用系统性预防用药的情况下 IFDs 发生率仍较低,提示预防策略存在优化空间。这些数据为实体瘤免疫治疗和 CAR-T 时代的感染风险提供了流行病学基准。
严重感染是儿科肿瘤发病率和死亡率的主要原因,尤其是接受大剂量化疗的儿童。高危神经母细胞瘤(HR-NB)提供了长期多模式治疗的范例模型,但最近描述其治疗过程中严重感染的负担和时间的数据有限。程序:我们回顾性回顾了 2002 年至 2021 年间根据 SIOPEN/HR-NBL1 方案在 IRCCS Istituto Giannina Gaslini(意大利热那亚)诊断和治疗的连续 184 例 HR-NB 患者。根据国际标准,严重感染事件被定义为血流感染(BSI)和侵袭性真菌病(IFD)。分析了每 100 个风险患者日 (pdr) 的发病率和特定阶段的分布(诱导、巩固、维持)。
在 80,202 个处于风险的患者日中,记录了 104 例严重感染(累计发生率为 56.5%)。 BSI 占事件的 93.3%,主要是革兰氏阳性 (55.8%) 和革兰氏阴性 (37.5%) 病原体; 6.7% 是 IFD。诱导期的发病率最高,而巩固期(造血干细胞移植)的每次 pdr 感染率最高。大约 70% 的 BSI 发生在非中性粒细胞减少的患者中,并且与中心静脉导管 (CVC) 相关;在中性粒细胞减少病例 (30%) 中,一半与 CVC 相关。感染相关死亡率为 1.1%(184 例中有 2 例)。
BACKGROUND: Severe infections are a leading cause of morbidity and mortality in pediatric oncology, especially among children receiving high-dose chemotherapy. High-risk neuroblastoma (HR-NB) provides a paradigmatic model of prolonged multimodal treatment, yet recent data describing the burden and timing of severe infections during its therapeutic course are limited. PROCEDURE: We retrospectively reviewed 184 consecutive HR-NB patients diagnosed and treated at the IRCCS Istituto Giannina Gaslini (Genoa, Italy) according to the SIOPEN/HR-NBL1 protocol between 2002 and 2021. Severe infectious events were defined as bloodstream infections (BSI) and invasive fungal diseases (IFDs) according to international criteria. Incidence rates per 100 patient-days at risk (pdr) and phase-specific distributions (induction, consolidation, maintenance) were analyzed. RESULTS: Over 80,202 patient-days at risk, 104 severe infections were recorded (cumulative incidence 56.5%). BSI represented 93.3% of events, predominantly Gram-positive (55.8%) and Gram-negative (37.5%) pathogens; 6.7% were IFDs. The induction phase accounted for the highest incidence, while consolidation (hematopoietic stem cell transplantation) showed the highest infection rate per pdr. Approximately 70% of BSI occurred in non-neutropenic patients and were central venous catheter (CVC) related; in neutropenic cases (30%), half were CVC associated. Infection-related mortality was 1.1% (two out of 184). CONCLUSIONS: Severe infections remain frequent and clinically significant complications in HR-NB therapy, though infection-related mortality was low. The low incidence of IFDs despite the absence of systematic prophylaxis suggests potential optimization of preventive strategies. These data provide an epidemiologic benchmark for infection risk in the era of immunotherapy and CAR-T approaches for solid tumors.
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