Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia
N Engl J Med, 2018 · International, multicenter, single-arm, phase 2 registration trial
Clinical question
What is the efficacy and toxicity profile of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in relapsed/refractory B-ALL?
What the trial found
Tisagenlecleucel achieved durable remissions in relapsed/refractory B-ALL, but was accompanied by high rates of cytokine release syndrome requiring standardized ICU management with tocilizumab.
Current guideline position
FDA and ASTCT consensus guidelines incorporate the ELIANA toxicity management algorithms (tocilizumab +/- corticosteroids) as the cornerstone of CAR-T critical care.
Clinical interpretation
Pivotal landmark trial establishing the therapeutic reality of CAR T-cell therapy and defining the protocolized management of Cytokine Release Syndrome (CRS) in critical care.
Host immune defects, neutropenic sepsis, acute respiratory failure (PJP/Aspergillus), tumor lysis syndrome, leukostasis, CAR-T CRS/ICANS, and ICU triage.
Life-threatening organ dysfunction caused by a dysregulated host response to infection — recognized by an acute rise in SOFA score, not by infection plus fever alone.
The subset of sepsis with profound circulatory and cellular/metabolic abnormality — clinically identified by a vasopressor requirement to maintain MAP ≥ 65 mmHg plus lactate > 2 mmol/L despite adequate fluid resuscitation.