背景:CD19靶向的嵌合抗原受体(CAR)-T细胞治疗涉及靶向B细胞的患者来源的T细胞,导致B细胞耗竭和发育不全。在对jirovecii肺孢子虫(Pj)的免疫中,CD4+T细胞和,最近,B细胞,通常被认为是重要的。B细胞向CD4+T细胞的抗原呈递特别重要。当CD4+T细胞计数>200/μL时,甲氧苄啶-磺胺甲恶唑(TMP/SMX)预防Pj肺炎(PJP)通常会停止。这里我们报告第一个病例,根据我们的知识,CAR-T细胞治疗后CD4+T细胞计数>200/μL的患者的PJP。
方法:一名14岁女孩在脐血移植(CBT)治疗复发性前体B细胞急性淋巴细胞白血病(B-ALL)后出现噬血细胞性淋巴组织细胞增生症(HLH)。CBT后21个月,她被诊断为骨髓和中枢神经系统联合复发。患者接受CD19靶向CAR-T细胞疗法治疗复发。CAR-T细胞治疗后,患者仍处于缓解状态,继续接受TMP/SMX预防PJP.CAR-T细胞治疗后7个月,恢复CD4+T细胞并停用TMP/SMX。B细胞再生障碍持续存在。CAR-T细胞治疗后10个月,患者出现PJP。患者也被认为在PJP发作时具有巨噬细胞过度活化。用免疫球蛋白治疗,TMP/SMX,开始使用泼尼松龙,患者的症状迅速改善。
结论:本病例患者在CAR-T细胞治疗后,尽管CD4+T细胞计数>200/μL,可能是由于CAR-T细胞治疗后B细胞耗竭引起的CD4+T细胞活化不足以及CBT后反复出现的异常巨噬细胞免疫反应所致。根据每种情况,确定TMP/SMX在CAR-T细胞治疗后预防的持续时间很重要,以及CD4+T细胞计数。
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.