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.