时间标签:数据日期 2026-10-31 · 生成时间 2026-11-01 05:30(Asia/Shanghai)| 检索窗口 PubMed edat 2026/10/28–2026/10/31 | 情报发生日期 2026-10-31
研究问题
Treatment of relapsed/refractory PTLD remains difficult and is still associated with poor outcomes [].;CD19‐CAR T‐cell therapy has revolutionized treatment of aggressive B‐cell lymphomas in immunocompetent patients [, ], however its application in SOT recipients remains limited due to concerns regarding efficacy related to ongoing immunosuppressive therapy (IST) and risk of graft rejection.;However, a major challenge remains the risk of graft rejection, reported in more than 10% of patients [] and optimal management of baseline immunosuppression remains to be defined.
方法
The patient received a first line therapy with Rituximab 375 mg/m2 for four weeks achieving complete remission (CR), followed by four courses of rituximab monotherapy every 21 days [].;To experimentally test this hypothesis, we performed CD19‐CAR T cell killing assays in vitro in the presence or absence of tacrolimus or everolimus.;OCI‐AML2‐CD19 cells were co‐cultured with CD19.CD28z CAR T cells at an effector‐to‐target (E:T) ratio of 2:1 in the presence or absence of tacrolimus and everolimus over a 7‐days in vitro killing assay.
核心结论
A 40‐year‐old female patient was diagnosed with stage IIE (breast) lymphoma associated with immune deficiency and dysregulation per WHO 2022 classification [], previously known as monomorphic PTLD, 3 years after SPK transplantation for type 1 diabetes and end‐stage renal disease secondary to diabetic nephropathy while on IST with mycophenolate mofetil (MMF) and tacrolimus.;IST was decreased, MMF was discontinued and replaced by low dose corticosteroids.;Tacrolimus was discontinued 15 days before leukoapheresis and prednisone increased at 10 mg/day. ‖ 结论:Collectively, our data support the use of mTOR‐based, CNI‐free immunosuppression during CAR T‐cell therapy of hematological malignancies in SOT recipients.
局限
Although causality cannot be established, we cannot exclude the possibility that reintroducing tacrolimus contributed to the subsequent relapse by impairing residual CAR T‐cell activity and/or endogenous antitumor immunity.
对本项目的价值
★☆☆☆☆ 炎症衰老是几乎所有慢性老年病的公共通路,也是最有希望做「抗炎但保留免疫」解耦的靶点。
全文来源
PMC JATS 全文(正文 11,825 字符,已过标题/DOI 逐字归属校验)
原文题录
- 英文标题:Calcineurin Inhibitor-Free, mTOR-Based Immunosuppression in Chimeric Antigen Receptor T-Cell Therapy for Post-Transplant Lymphoproliferative Disorder.
- 期刊与标识:EJHaem · PMID 42959460 · DOI 10.1002/jha2.70437
A 级证据分级:A 级(同行评议人体研究)
本文属人体研究证据,但需注意:观察性或小样本干预的结论不等于已证实临床获益;效应量与长期安全性仍需更大规模、更长随访的试验验证。
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