Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.
Cancer Rep (Hoboken). 2023 Oct;6(10):e1885. doi: 10.1002/cnr2.1885. Epub 2023 Aug 10.
CD19-targeted chimeric antigen receptor (CAR)-T cell therapy involves administration of patient-derived T cells that target B cells, resulting in B-cell depletion and aplasia. In immunity against Pneumocystis jirovecii (Pj), CD4+ T cells and, more recently, B cells, are generally considered important. Antigen presentation by B cells to CD4+ T cells is particularly important. Trimethoprim-sulfamethoxazole (TMP/SMX) for Pj pneumonia (PJP) prophylaxis is generally discontinued when the CD4+ T-cell count is >200/μL. Here we report the first case, to our knowledge, of PJP in a patient with a CD4+ T cell count of >200/μL after CAR-T cell therapy.
A 14-year-old girl developed hemophagocytic lymphohistiocytosis (HLH) after cord blood transplantation (CBT) for relapsed precursor B-cell acute lymphoblastic leukemia (B-ALL). Twenty-one months after CBT, she was diagnosed with combined second relapse in the bone marrow and central nervous system. The patient was treated with CD19-targeted CAR-T cell therapy for the relapse. After CAR-T cell therapy, the patient remained in remission and continued to receive TMP/SMX for PJP prophylaxis. Seven months after CAR-T cell therapy, CD4+ T cells recovered and TMP/SMX was discontinued. The B-cell aplasia persisted. Ten months after CAR-T cell therapy, the patient developed PJP. The patient was also considered to have macrophage hyperactivation at the onset of PJP. Treatment with immunoglobulin, TMP/SMX, and prednisolone was initiated, and the patient's symptoms rapidly ameliorated.
The patient in the present case developed PJP despite a CD4+ T-cell count of >200/μL after CAR-T cell therapy, probably because of inadequate CD4+ T-cell activation caused by B-cell depletion after CAR-T cell therapy and repeated abnormal macrophage immune responses after CBT. It is important to determine the duration of TMP/SMX for prophylaxis after CAR-T cell therapy according to each case, as well as the CD4+ T-cell count.
CD19 靶向嵌合抗原受体 (CAR)-T 细胞疗法涉及输注靶向 B 细胞的患者源性 T 细胞，从而导致 B 细胞耗竭和再生障碍。在针对卡氏肺孢子菌（Pj）的免疫中，CD4+T 细胞以及最近的 B 细胞通常被认为是重要的。B 细胞向 CD4+T 细胞的抗原呈递尤其重要。当 CD4+T 细胞计数＞200/μL 时，通常停止使用复方磺胺甲噁唑（TMP/SMX）预防卡氏肺孢子菌肺炎（PJP）。在此，我们报告首例 CAR-T 细胞治疗后 CD4+T 细胞计数＞200/μL 时发生 PJP 的病例。
一名 14 岁女孩因复发前体 B 细胞急性淋巴细胞白血病（B-ALL）行脐带血移植（CBT）后发生噬血细胞性淋巴组织细胞增多症（HLH）。CBT 后 21 个月，她被诊断为骨髓和中枢神经系统合并二次复发。该患者接受 CD19 靶向 CAR-T 细胞治疗复发。CAR-T 细胞治疗后，患者持续缓解并继续接受 TMP/SMX 预防 PJP。CAR-T 细胞治疗后 7 个月，CD4+T 细胞恢复，停用 TMP/SMX。B 细胞再生障碍持续存在。CAR-T 细胞治疗后 10 个月，患者发生 PJP。患者在 PJP 发病时也被认为存在巨噬细胞过度激活。开始给予免疫球蛋白、TMP/SMX 和泼尼松龙治疗，患者症状迅速改善。
本例患者在 CAR-T 细胞治疗后 CD4+T 细胞计数＞200/μL 时发生 PJP，可能是由于 CAR-T 细胞治疗后 B 细胞耗竭导致 CD4+T 细胞激活不足，以及 CBT 后反复出现异常的巨噬细胞免疫反应。根据每个病例以及 CD4+T 细胞计数，确定 CAR-T 细胞治疗后 TMP/SMX 预防的持续时间非常重要。
