2.2 CASE 2
A 22-year old male with relapsed/refractory Philadelphia chromosome negative B-cell ALL underwent Tisa-cel therapy in 2020. After a bridging therapy with cyclophosphamide, vincristine and dexamethasone, he received lymphodepletion with fludarabine and cyclophosphamide. At the time of Tisa-cel infusion the patient was afebrile with a baseline ferritin of 6905 ng/mL. He developed a grade 1 CRS six hours after infusion, progressing to grade 2 on day +2, and was treated with three doses of tocilizumab. Plasma cytokine levels showed high values of IL-15, GM-CSF and IL-6. Both symptoms and cytokine levels rapidly improved after administration of tocilizumab.
On day +11 he presented with a new episode of fever, high flow oxygen therapy requirements, impaired renal and liver function, increased ferritin levels (peak 800,000 ng/mL on day +14) and coagulopathy. CAR-T cells expansion in PB was detected (4,141 CAR-T/mL on day +14). At this point, the patient met criteria of CAR-T related HLH/MAS and further studies were performed, showing high levels of soluble CD25 (>10,000 pg/mL), IL-18 (>10,000 pg/mL), INF-gamma (1,365 pg/mL) and TNF-alpha (241 pg/mL).
The patient was transferred to the ICU and was managed with supportive therapy, dexamethasone 20mg/6h from day +14, etoposide 150mg/m2 on days +15 and +18 and anakinra 100mg/12h from day +15 to day +17, with progressive improvement. Dexamethasone was slowly tapered and discontinued on day +44 (Figure 2).
Despite successful management of CAR-T related HLH, he died on day +47 due to a necrotizing pancreatitis in the context of extramedular ALL progression.