Department of Hematology and Oncology, University Hospital, LMU Munich, Munich, Germany.
Laboratory for Translational Cancer Immunology, LMU Gene Center, Munich, Germany.
BMC Infect Dis. 2021 Jan 28;21(1):121. doi: 10.1186/s12879-020-05755-4.
Prolonged myelosuppression following CD19-directed CAR T-cell transfusion represents an important, yet underreported, adverse event. The resulting neutropenia and multifactorial immunosuppression can facilitate severe infectious complications.
We describe the clinical course of a 59-year-old patient with relapsed/refractory DLBCL who received Axicabtagene-Ciloleucel (Axi-cel). The patient developed ASTCT grade I CRS and grade IV ICANS, necessitating admission to the neurological ICU and prolonged application of high-dose corticosteroids and other immunosuppressive agents. Importantly, neutropenia was profound (ANC < 100/μl), G-CSF-refractory, and prolonged, lasting more than 50 days. The patient developed severe septic shock 3 weeks after CAR transfusion while receiving anti-fungal prophylaxis with micafungin. His clinical status stabilized with broad anti-infective treatment and intensive supportive measures. An autologous stem cell backup was employed on day 46 to support hematopoietic recovery. Although the counts of the patient eventually started to recover, he developed an invasive pulmonary aspergillosis, which ultimately lead to respiratory failure and death. Postmortem examination revealed signs of Candida glabrata pancolitis.
This case highlights the increased risk for fatal infectious complications in patients who present with profound and prolonged cytopenia after CAR T-cell therapy. We describe a rare case of C. glabrata pancolitis associated with multifactorial immunosuppression. Although our patient succumbed to a fatal fungal infection, autologous stem cell boost was able to spur hematopoiesis and may represent an important therapeutic strategy for DLBCL patients with CAR T-cell associated bone marrow aplasia who have underwent prior stem cell harvest.
CD19 导向的 CAR T 细胞输注后持续的骨髓抑制是一种重要但报道较少的不良事件。由此导致的中性粒细胞减少和多因素免疫抑制可导致严重的感染并发症。
我们描述了一名 59 岁复发/难治性弥漫性大 B 细胞淋巴瘤患者接受 Axicabtagene-Ciloleucel（Axi-cel）治疗的临床过程。该患者发生了 ASTCT Ⅰ级细胞因子释放综合征（CRS）和 4 级免疫效应细胞相关神经毒性综合征（ICANS），需要入住神经重症监护病房，并长期应用大剂量皮质类固醇和其他免疫抑制剂。重要的是，中性粒细胞减少严重（ANC<100/μl）、对 G-CSF 无反应且持续时间长，超过 50 天。CAR 输注后 3 周，患者发生严重败血症性休克，同时接受米卡芬净预防真菌感染。广谱抗感染治疗和强化支持治疗使患者的临床状况稳定下来。在第 46 天，患者接受了自体干细胞支持以促进造血恢复。尽管患者的计数最终开始恢复，但他发生了侵袭性肺曲霉病，最终导致呼吸衰竭和死亡。尸检显示出 Candida glabrata 全结肠炎的迹象。
本病例强调了 CAR T 细胞治疗后出现严重和持久血细胞减少的患者发生致命性感染并发症的风险增加。我们描述了一例罕见的与多因素免疫抑制相关的 C. glabrata 全结肠炎病例。尽管我们的患者死于致命性真菌感染，但自体干细胞支持能够刺激造血，可能代表了既往进行过干细胞采集的 CAR T 细胞相关骨髓再生不良的 DLBCL 患者的重要治疗策略。
