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:Toxoplasmosis Beyond Transplantation: Diagnostic and Prevention Challenges in a Patient Receiving Targeted Immunomodulators.
Toxoplasmosis Beyond Transplantation: Diagnostic and Prevention Challenges in a Patient Receiving Targeted Immunomodulators.
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弓形虫病长期以来被认为是免疫功能低下宿主的严重并发症,尤其见于晚期HIV/AIDS、造血干细胞移植(HSCT)、实体器官移植(SOT)及血液系统恶性肿瘤患者。CAR-T 细胞疗法、单克隆抗体和小分子抑制剂等靶向免疫调节剂迅速扩展,正在移植以外形成新的易感人群。
我们报告一例9岁高危B细胞急性淋巴细胞白血病(B-ALL)男童,出现持续发热和巨噬细胞活化综合征(MAS)。经广泛检查未能明确病因后,在骨髓穿刺中偶然通过形态学发现速殖子,并经刚地弓形虫PCR证实为播散性急性弓形虫病。本病例展示了非移植、接受免疫调节治疗宿主中弓形虫病这一新兴威胁,并支持三项核心风险缓解策略。第一,所有开始靶向免疫治疗的患者均应进行基线弓形虫IgG和IgM血清学检测;需注意B细胞耗竭或低丙种球蛋白血症会使IgG检测可靠性下降,而免疫功能低下者的IgM可能假阴性、延迟出现或持续阳性。第二,当常规诊断无结果时,应尽早对临床相关部位进行靶向PCR,或采用宏基因组二代测序。第三,预防需采取组合策略:基线筛查、对血清阴性者开展患者教育,以及对血清阳性者使用甲氧苄啶-磺胺甲噁唑预防,可结合连续qPCR监测。弓形虫病已不再是移植患者独有的风险。随着靶向免疫调节剂改变风湿病学、肿瘤学、神经病学和自身免疫病等领域的临床实践,感染病专科医生应牵头提升跨专科认知、建立指南和注册数据库,以明确这些不断扩大的患者群体中弓形虫病的真实负担。
Toxoplasmosis has long been recognized as a serious complication in immunocompromised host, particularly those with advanced HIV/AIDS, hematopoietic stem-cell transplantation (HSCT), solid-organ transplant (SOT), and hematological malignancies. The rapid expansion of targeted immunomodulators, including chimeric antigen receptor T-cell (CAR-T) therapies, monoclonal antibodies, and small-molecule inhibitors, is creating new at-risk populations beyond traditional transplant settings.
We present a 9-year-old boy with high-risk B-cell acute lymphoblastic leukemia (B-ALL), who developed prolonged fever and macrophage activation syndrome (MAS). After an extensive unrevealing workup, disseminated acute toxoplasmosis was identified incidentally on bone marrow aspirate via morphologic identification of tachyzoites and confirmed by Toxoplasma gondii PCR. This case exemplifies the emerging threat of toxoplasmosis in non-transplant immunomodulated hosts and supports three core mitigation strategies. First, baseline Toxoplasma IgG and IgM serology should be obtained in all patients initiating targeted immunotherapy, recognizing that B-cell depletion or hypogammaglobulinemia may render IgG unreliable, and that IgM may be falsely negative, delayed, or persistently positive in immunocompromised individuals.
Second, targeted PCR from clinically relevant compartments or metagenomic next-generation sequencing when conventional diagnostics is unrevealing should be applied early. Third, prevention requires a bundled approach: baseline screening, patient education for seronegative individuals, and trimethoprim-sulfamethoxazole prophylaxis with or without serial qPCR monitoring for seropositive patients.
Toxoplasmosis is no longer a transplant-exclusive concern. As targeted immunomodulators reshape practice across rheumatology, oncology, neurology, and autoimmune disease, infectious diseases specialists must lead efforts to raise cross-specialty awareness, establish guidelines, and build registries to define the true burden of toxoplasmosis in these growing populations.
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