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:CD7 CAR-T Cell as Bridging Therapy for Successful Allogeneic Hematopoietic Stem Cell Transplantation in Relapsed/Refractory T Lymphoblastic Leukemia/ Lymphoma: A Case Report and Literature Review.
CD7 CAR-T Cell as Bridging Therapy for Successful Allogeneic Hematopoietic Stem Cell Transplantation in Relapsed/Refractory T Lymphoblastic Leukemia/ Lymphoma: A Case Report and Literature Review.
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复发/难治性T细胞急性淋巴细胞白血病/淋巴瘤(R/R T-ALL/LBL)预后极差。达到微小残留病(MRD)阴性完全缓解(CR)后接受异基因造血干细胞移植(allo-HSCT),是实现长期缓解的唯一可能。然而,传统挽救化疗很少能使患者达到MRD阴性。因此,亟需新的桥接策略来清除MRD并实现移植。 病例报告:我们报告一例51岁男性T-ALL/LBL患者,尽管接受多线挽救治疗,仍为MRD阳性。作为移植桥接治疗,患者在淋巴细胞清除后接受来自其HLA 9/10匹配儿子的供者来源CD7CAR-T 细胞治疗。第3天发生3级细胞因子释放综合征,经处理后缓解;未观察到神经毒性。第15天骨髓评估证实形态学完全缓解及MRD阴性,且缓解持续。随后患者接受同一供者提供的清髓性单倍体相合HSCT。中性粒细胞于第+14天植入,血小板于第+45天植入。未发生急性或慢性移植物抗宿主病。连续监测至第+150天显示MRD阴性缓解和供者嵌合状态持续维持。
序贯CD7 CAR-T 治疗后进行巩固性allo-HSCT,是高危R/R T-ALL/LBL患者一种有前景的治愈策略,可清除单纯化疗无法清除的MRD。本病例显示供者来源CD7 CAR-T 作为移植桥接治疗具有可行性和疗效,且毒性可管理。仍需开展较大样本前瞻性研究,进一步验证该策略并优化时机和预处理方案。
BACKGROUND Relapsed/refractory T-cell acute lymphoblastic leukemia/lymphoma (R/R T-ALL/LBL) carries an exceptionally poor prognosis. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) after achieving minimal residual disease (MRD)-negative complete remission (CR) offers the only possibility of long-term remission.
However, conventional salvage chemotherapy rarely achieves MRD negativity.
Thus, novel bridging strategies to eliminate MRD and enable transplant are urgently needed. CASE REPORT We report the case of a 51-year-old man with T-ALL/LBL who remained MRD-positive despite multiple lines of salvage therapy. As a bridge to transplant, he received donor-derived CD7 chimeric antigen receptor T cells (CAR-T) from his 9/10 HLA-matched son after lymphodepletion. Grade 3 cytokine release syndrome occurred on day 3 and resolved with management; no neurotoxicity was observed. Bone marrow evaluation on day 15 confirmed morphological complete remission and MRD negativity, which proved sustained. The patient then underwent myeloablative haploidentical HSCT from the same donor.
Neutrophil engraftment occurred on day +14 and platelet engraftment on day +45. No acute or chronic graft-versus-host disease developed. Serial monitoring through day +150 demonstrated sustained MRD-negative remission and donor chimerism. CONCLUSIONS Sequential CD7 CAR-T therapy followed by consolidative allo-HSCT is a promising curative approach for high-risk R/R T-ALL/LBL patients, enabling MRD clearance not achievable with chemotherapy alone.
This case highlights the feasibility and efficacy of donor-derived CD7 CAR-T as a bridge to transplant, with manageable toxicity. Prospective studies with larger cohorts are needed to further validate this strategy and optimize timing and conditioning.
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