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.