Figure 1.
Clinical, biochemical and correlative analysis for patient 1. (A) Time course of events following CAR T-cell infusion, including adverse events, infectious complications, stem cell infusion, and trends of inflammatory markers and blood counts. (B) Therapeutic strategies employed for managing CAR T-cell–related toxicities. For the first episode of CRS and IEC-HS, the patient received tocilizumab 8 mg/kg for 2 days, 10 mg every 6 hours of dexamethasone tapered over 10 days (tapered), and anakinra 100 mg every 6 hours tapered over 7 days. In the second episode of IEC-HS, the patient received 1 g of methylprednisolone for 3 days with a prolonged taper, along with a dexamethasone taper. Anakinra was started at 100 mg every 6 hours and tapered to every 24 hours over 1 week. Ruxolitinib was initiated at 5 mg daily and increased to twice daily, and was stopped after a week because of concerns about gastrointestinal bleeding. Two doses of emapalumab (1 mg/kg) were administered after high doses of steroids and anakinra failed to improve the clinical course. Finally, the patient received etoposide 50 mg/m2 3 days before death. (C) Immunophenotyping of BM and peripheral blood, showing CAR T-cell expansion, gated on CD3+ viable lymphocytes. (D) Immunophenotyping on day 62 (1 day before the patient died), demonstrating the expansion of mononuclear type cells. (E) H&E staining of BM on day 30 after CAR T-cell therapy but before stem cell boost, showing marked paucicellularity (<5%) (left) and immunohistochemistry demonstrating scattered CD3+ T cells (middle), and PU.1+ cells, which are overexpressed in monocytes, dendritic cells, and histiocytes (right). ALC, absolute lymphocyte count; ANC, absolute neutrophil count; CMV, cytomegalovirus; CRP, C-reactive protein; GGO, ground glass opacity; H&E, hematoxylin and eosin.

Clinical, biochemical and correlative analysis for patient 1. (A) Time course of events following CAR T-cell infusion, including adverse events, infectious complications, stem cell infusion, and trends of inflammatory markers and blood counts. (B) Therapeutic strategies employed for managing CAR T-cell–related toxicities. For the first episode of CRS and IEC-HS, the patient received tocilizumab 8 mg/kg for 2 days, 10 mg every 6 hours of dexamethasone tapered over 10 days (tapered), and anakinra 100 mg every 6 hours tapered over 7 days. In the second episode of IEC-HS, the patient received 1 g of methylprednisolone for 3 days with a prolonged taper, along with a dexamethasone taper. Anakinra was started at 100 mg every 6 hours and tapered to every 24 hours over 1 week. Ruxolitinib was initiated at 5 mg daily and increased to twice daily, and was stopped after a week because of concerns about gastrointestinal bleeding. Two doses of emapalumab (1 mg/kg) were administered after high doses of steroids and anakinra failed to improve the clinical course. Finally, the patient received etoposide 50 mg/m2 3 days before death. (C) Immunophenotyping of BM and peripheral blood, showing CAR T-cell expansion, gated on CD3+ viable lymphocytes. (D) Immunophenotyping on day 62 (1 day before the patient died), demonstrating the expansion of mononuclear type cells. (E) H&E staining of BM on day 30 after CAR T-cell therapy but before stem cell boost, showing marked paucicellularity (<5%) (left) and immunohistochemistry demonstrating scattered CD3+ T cells (middle), and PU.1+ cells, which are overexpressed in monocytes, dendritic cells, and histiocytes (right). ALC, absolute lymphocyte count; ANC, absolute neutrophil count; CMV, cytomegalovirus; CRP, C-reactive protein; GGO, ground glass opacity; H&E, hematoxylin and eosin.

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