Observational studyBlood advances2026
HLH-like syndromes associate with increased risk of death and CD19- relapse after CAR T in pediatric B-ALL.
Observational study in Blood advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
abstractWe previously reported poor long-term outcomes in patients with B-acute lymphoblastic leukemia (B-ALL) who developed hemophagocytic lymphohistiocytosis (HLH)-like toxicities (HLH-LT) after treatment with tisagenlecleucel. Since then, a consensus definition, immune effector cell-associated HLH-like syndrome (IEC-HS), was developed. Here, we report results from a multicenter retrospective study of children and young adults with B-ALL treated with tisagenlecleucel between 2018 and 2023, describing the incidence, diagnostic overlap, clinical phenotypes, and associated long-term outcomes of HLH-like syndromes. Of 154 tisagenlecleucel recipients, 14.9% met IEC-HS criteria, 21.4% met HLH-LT criteria, and 13% were identified as having HLH by treating institutions in the electronic health record; 10% met all definitions. Each HLH-like syndrome was associated with shortened overall survival and event-free survival, adjusting for baseline disease burden (P< .0001). Those with any HLH-like syndrome experienced 1-year cumulative incidence of nonresponse/relapse of 60% (95% confidence interval [CI], 43.1-76.9) vs 28.2% (95% CI, 20.0-36.5), P< .001, and nonrelapse mortality of 11.4% (95% CI, 0.7-22.1) vs 0% (95% CI, 0-0), P< .001, compared with those without. In those with high disease burden, patients with any HLH-like syndrome had a 1-year cumulative incidence of CD19- relapse of 65.2% (95% CI, 44.7-85.8) vs 2% (95% CI, 0-6.4) in those with no HLH-like syndrome, P< .001. Furthermore, adjusting for disease burden, any HLH-like syndrome was independently predictive of CD19- relapse with a hazard ratio of 8.10 (95% CI, 3.6-18.4), P< .001. These findings demonstrate partial definitional overlap of HLH-like syndromes and the prognostic significance of IEC-HS and identify CD19- relapse and nonrelapse mortality as key outcome drivers.
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