PMC9888489_01
Case report timeline. The table offers an overview of the patient's history, treatment lines (A) and corresponding marrow blast count (B). The percentage of bone marrow blasts was evaluated at significant time-points, namely at diagnosis, post-induction, post-transplant, at disease relapse, during bridging and after CAR-T infusion. At the last follow-up, the patient is still in molecular remission and in persistent B-cell aplasia.
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She still receives ponatinib maintenance with excellent tolerance, except for a 10-day discontinuation due to a transient G4 neutropenia.  Figure 1  summarizes the case timeline.
(A) Longitudinal evaluation of total CD3+ T cells, anti-CD19 CAR-T cells, CD19+ B cells and released cytokines in the patient's peripheral blood. Absolute counts were evaluated by flow cytometry at several time-points for up to 1 year after CAR-T cell infusion. The pharmacokinetics shows a remarkable CAR-T cell expansion in the first week following infusion (coinciding with CRS onset and resolution), with engineered cells representing nearly 40% of overall T cells, and a subsequent drop in CAR-T cells over time. At day 270, the patient still has a subset of CAR-T cells accounting for around 1% of the total T-cell count. At the time of last follow-up, circulating CAR-T cells had decreased below the detection limit of the assay but B-cell aplasia persists. (B) Evaluation of serum cytokines/chemokines concentrations in the first three weeks after CAR-T cell infusion. The analysis shows a significant peak occurring within the first week after treatment.
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We longitudinally monitored the patient's CAR-T cell expansion and their subsequent persistence by flow cytometry and plotted the data over time in  Figure 2A . Peak levels of inflammatory cytokines and chemokines occurred within the first week after the CAR T-cell infusion, with particularly high levels of monocyte chemoattractant protein-1 (MCP-1), interferon gamma-induced protein 10 kDa (IP-10), interleukin-6 (IL-6) and interferon-gamma (IFN- gamma,  Figure 2B ).