Cytokine release syndrome (CRS) is one of the major acute complications caused by massive cytokine release after chimeric antigen receptor (CAR) T-cell therapy. Patients with tumor masses were considered at high risk of local CRS induced by the expansion of CAR T cells in the tumor masses. However, even patients without any tumor burden around the neck are at risk of developing cervical edema as local CRS, which can lead to life-threatening airway obstruction. Here, we present the case of a 15-year-old boy who developed cervical edema as a local CRS after CAR T-cell therapy for refractory acute lymphoblastic leukemia. Despite administration of tocilizumab and methylprednisolone for persistent fever as a symptom of systemic CRS after CAR T-cell therapy, cervical edema occurred and extended to the larynx, resulting in dysphagia and hoarseness. Dexamethasone was remarkably effective, and the laryngeal symptoms resolved within a few hours. Local cytokine syndrome showed exacerbation with tocilizumab but exhibited considerable improvement with dexamethasone administration.

Cytokine release syndrome (CRS), which may be associated with fever, hypotension, hypoxia, and organ damage, is caused by a massive cytokine release after chimeric antigen receptor (CAR)-T cell therapy. We present the case of a patient who developed severe bloody diarrhea due to CRS after CAR-T cell infusion. A 10-year-old boy presented with a second relapse of B-cell precursor acute lymphoblastic leukemia 6 months after hematopoietic stem cell transplantation from an unrelated donor. CAR-T cells (tisagenlecleucel) were infused at the third complete remission after salvage chemotherapy. While fever >39°C was sustained from day 4, circulatory and respiratory status remained stable. However, he experienced severe bloody diarrhea. There was no evidence of infection; lower gastrointestinal (GI) endoscopy revealed extensive edema with erosion and ulceration, suggestive of non-specific intestinal inflammation. Thus, we considered CRS-associated grade 3 GI damage and administered a single dose of tocilizumab for grade 2 CRS, followed by 4 days of corticosteroids. Afterwards, no fever or GI bleeding was observed. Biopsy of the intestinal mucosa revealed ulcerative change with a lack of epithelial cells, which may correspond to histologic grade 4 graft versus host disease (GVHD). However, diarrhea corresponded to stage 1 GVHD, and the GVHD risk after CAR-T cell infusion has been reported to be rare in clinical practice. Although severe GI symptoms associated with CRS after CAR-T therapy are rare, early tocilizumab use is recommended for non-infectious severe GI symptoms to avoid long-term corticosteroid use, which may reduce CAR-T cell efficacy.

Anaplastic large cell lymphoma (ALCL) is a rare form of non-Hodgkin’s lymphoma (NHL) in children, accounting for 10–15% of all NHL cases. ALCL is currently classified as follows: systemic anaplastic lymphoma kinase (ALK)-positive, systemic ALK-negative, primary cutaneous, and breast implant-associated ALCL. In children, systemic ALK-positive ALCL is the most common, and patients often present with extranodal involvement. We report a rare case of systemic ALK-positive ALCL with primary bone involvement in a 15-year-old male patient. Primary bone lymphoma is most commonly observed in diffuse large B-cell lymphoma and is extremely rare in systemic ALCL. Therefore, the clinical features and prognosis of primary bone ALCL remain unclear. Our patient had spontaneous remission of primary maxillary bone ALCL after gingival scraping but relapsed 12 months later with rib metastasis. Spontaneous remission of ALCL has been reported frequently in primary cutaneous ALCL and rarely in systemic ALCL. Our case demonstrates for the first time that systemic ALCL can also present as solitary bone involvement that can spontaneously remit. Because systemic ALCL is aggressive and has a risk of relapse, as in our case, it is important to consider ALCL in the differential diagnosis of primary bone lesions and to make a precise pathological diagnosis.

BackgroundCD19‐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.CaseA 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.ConclusionThe 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.