CELL INTELLIGENCE · 肿瘤细胞治疗研究

We previously reported poor long-term outcomes in patients with B-acute lymphoblastic leukemia (B-ALL) who developed hemophagocytic lymphohistiocytosis-like toxicities (HLH-LT) following 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 multi-center 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. Ten percent met all definitions. Each HLH-like syndrome was associated with shortened overall survival and event-free survival, adjusting for baseline disease burden (p<0.

0001). Those with any HLH-like syndrome experienced 1-year cumulative incidence of non-response/relapse of 60% (95% CI [43. 1-76. 9]) vs. 28. 2% (95% CI [20. 0-36. 5]), p<0. 001, and non-relapse mortality of 11. 4% (95% CI [0. 7- 22. 1]) vs. 0% (95% CI [0-0]), p<0. 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-negative 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<0. 001.

Further, adjusting for disease burden, any HLH-like syndrome was independently predictive of CD19-negative relapse with a hazard ratio of 8. 10 (95% CI [3. 6-18. 4]), p<0. 001.

These findings demonstrate partial definitional overlap of HLH-like syndromes and the prognostic significance of IEC-HS and identify CD19-negative relapse and non-relapse mortality as key outcome drivers.