HLH-like syndromes associate with increased risk of death and CD19-negative relapse post-CAR T in pediatric B-ALL

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.

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Journal
Blood Advances
Published
2026-07-17
DOI
https://doi.org/10.1182/bloodadvances.2026020511
Primary Topic
Autoimmune and Inflammatory Disorders Research
Type
article
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article

HLH-like syndromes associate with increased risk of death and CD19-negative relapse post-CAR T in pediatric B-ALL

Anant Vatsayan, Holly Pacenta, Christina Baggott, Michael R. Verneris et al.
Blood Advances
Autoimmune and Inflammatory Disorders Research
article

HLH-like syndromes associate with increased risk of death and CD19-negative relapse post-CAR T in pediatric B-ALL

Anant Vatsayan, Holly Pacenta, Christina Baggott, Michael R. Verneris, Christa Krupski, Samuel John, T. Laetsch, Gary Douglas Myers, Aimee C. Talleur, L. Nelson Sanchez‐Pinto, Elliot Stieglitz, Vanessa A. Fabrizio, Muna Qayed, Lena E. Winestone, Prakash Satwani, Challice Lee Bonifant, Soyang Kwon, Amy K. Keating, Susanne H.C. Baumeister, Xiaopei Lily Zeng, Rebecca Gardner, Snehit Prabhu, Jenna Rossoff, Nicole Karras, Crystal L. Mackall, Gabriela Llaurador Caraballo, Christine L. Phillips, Swati Naik, Julie-An M. Talano, Amy Moskop, Emily Egeler, Kevin O. McNerney, Kevin J. Curran, Liora M. Schultz
article en

Abstract

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.

Blood Advances
Northwestern University (US), Boston Children's Hospital (US), Seattle Children's Hospital (US), City Of Hope National Medical Center (US), St. Jude Children's Research Hospital (US), Memorial Sloan Kettering Cancer Center (US), Children's Hospital of Philadelphia (US), Children's National (US), Johns Hopkins University (US), Emory University (US), Palo Alto University (US), University of California, San Francisco (US), Baylor College of Medicine (US), Medical College of Wisconsin (US), Columbia University Irving Medical Center (US), Johns Hopkins Medicine (US), Cook Children's Medical Center (US), Southwestern Medical Center (US), Parker Institute for Cancer Immunotherapy (US), Aflac (United States) (US), Dana-Farber Cancer Institute (US), UCSF Benioff Children's Hospital (US), Children's Healthcare of Atlanta (US), Texas Children's Hospital (US), Southwestern Medical Center (US), University of Colorado Anschutz Medical Campus (US), University of Cincinnati (US), The University of Texas Southwestern Medical Center (US), Stanford University (US)
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Openalex Percentile: Top 9%
Autoimmune and Inflammatory Disorders Research
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