Pneumocystis jirovecii pneumonia after CD4+ T‐cell recovery subsequent to CD19‐targeted chimeric antigen receptor T‐cell therapy: A case report and brief review of literature

BACKGROUND: 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. CASE: 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. CONCLUSION: 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.