Ahrendsen Jared T, Sehgal Kartik, Sarangi Sasmit, Uhlmann Erik J, Varma Hemant, Arnason Jon, Avigan David
Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Division of Hematology and Medical Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
J Hematol. 2021 Oct;10(5):212-216. doi: 10.14740/jh903. Epub 2021 Oct 5.
Chimeric antigen receptor (CAR) T-cell therapy targeting cluster of differentiation (CD)19 has had a transformative impact on patient outcomes in a subset of patients with relapsed/refractory non-Hodgkin lymphoma. We present a patient with refractory large B-cell lymphoma in complete remission for 2 years following treatment with CD19-targeted CAR T-cell therapy, who presented with 2 weeks of progressive aphasia. Imaging revealed a left occipital brain lesion and biopsy demonstrated features diagnostic of progressive multifocal leukoencephalopathy. Further evaluation revealed severe hypogammaglobulinemia and a low CD4 count. She was treated with pembrolizumab and intravenous immunoglobulin resulting in decreased cerebrospinal fluid viral load without clinical improvement and died 8 weeks after presentation. This case highlights that there is potential for severe opportunistic infections after CAR T-cell therapy, including fatal progressive multifocal leukoencephalopathy. Strategies to enhance post-treatment immune reconstitution are essential to further harness the unique potency of CAR T-cell therapy.
靶向分化簇（CD）19的嵌合抗原受体（CAR）T细胞疗法已对一部分复发/难治性非霍奇金淋巴瘤患者的治疗结果产生了变革性影响。我们报告了一名难治性大B细胞淋巴瘤患者，在接受靶向CD19的CAR T细胞治疗后完全缓解了2年，随后出现了2周的进行性失语。影像学检查发现左枕叶脑病变，活检显示具有多灶性白质脑病进展的诊断特征。进一步评估发现严重低丙种球蛋白血症和CD4计数低。她接受了派姆单抗和静脉注射免疫球蛋白治疗，脑脊液病毒载量降低，但临床症状未改善，就诊8周后死亡。该病例突出表明，CAR T细胞治疗后存在发生严重机会性感染的可能性，包括致命的进行性多灶性白质脑病。加强治疗后免疫重建的策略对于进一步发挥CAR T细胞疗法的独特效力至关重要。
