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球孢子菌病、免疫球蛋白缺乏:CAR T细胞疗法治疗复发性淋巴瘤的安全性挑战。

Coccidioidomycosis, immunoglobulin deficiency: safety challenges with CAR T cells therapy for relapsed lymphoma.

作者信息

Zahid Umar, Shaukat Al-Aman, Hassan Nida, Anwer Faiz

机构信息

Department of Medicine, Division of Hematology, Oncology, Blood and marrow transplantation, University of Arizona, Tucson, AZ 85724, USA.

Department of Biostatistics, Mel & Enid Zuckerman College of Public Health, University of Arizona, Tucson, AZ 85724, USA.

出版信息

Immunotherapy. 2017 Oct;9(13):1061-1066. doi: 10.2217/imt-2017-0070.

Abstract

Treatment of patients with relapsed or refractory lymphoma may require allogenic hematopoietic stem cell transplant (HSCT), but treatment of post-transplant relapse disease remains very challenging. Donor lymphocyte infusion and blinatumomab have been used with limited success for the treatment of relapse. Initial data on donor-derived CAR T cells has shown this modality to be safe and highly effective in various hematological malignancies. We present a case of a patient with highly refractory, transformed follicular lymphoma who failed both autologous and allogenic HSCT. Patient achieved long-lasting complete remission with the use of donor origin CD19 CAR T-cell therapy, without any evidence of graft-versus-host disease flare. Our patient later developed disseminated coccidioidomycosis and persistent hypogammaglobulinemia. Immunotherapy using CD19 CAR T cells can be a highly effective salvage modality, especially in cases of focal lymphoma relapse. Long-term immunosuppression secondary to B cell lymphopenia, hypogammaglobulinemia, immunoglobulin subclass deficiency, fungal infections and other infectious complications need to be monitored and promptly treated as indicated.

摘要

复发或难治性淋巴瘤患者的治疗可能需要异基因造血干细胞移植(HSCT),但移植后复发疾病的治疗仍然极具挑战性。供体淋巴细胞输注和博纳吐单抗用于复发治疗的效果有限。关于供体来源的嵌合抗原受体(CAR)T细胞的初步数据表明,这种治疗方式在各种血液系统恶性肿瘤中安全且高效。我们报告一例高度难治性转化型滤泡性淋巴瘤患者,其自体和异基因HSCT均失败。该患者使用供体来源的CD19 CAR T细胞疗法实现了持久的完全缓解,且无任何移植物抗宿主病复发迹象。我们的患者后来发生播散性球孢子菌病和持续性低丙种球蛋白血症。使用CD19 CAR T细胞进行免疫治疗可能是一种高效的挽救治疗方式,尤其是在局灶性淋巴瘤复发的病例中。继发于B细胞淋巴细胞减少、低丙种球蛋白血症、免疫球蛋白亚类缺乏、真菌感染和其他感染并发症的长期免疫抑制需要进行监测,并根据指征及时治疗。

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