REVIEW article
Front. Oncol.
Sec. Pediatric Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1631557
This article is part of the Research TopicCritical Complications In Pediatric Oncology and Hematopoietic Cell Transplant - Volume IIIView all 11 articles
Treating and Triggering Hyperinflammation: Tackling Hemophagocytic Lymphohistiocytosis (HLH) and HLH-like syndromes in the Pediatric Cell Therapy and Critical Care Setting
Provisionally accepted
Holly Wobma1,2
Lauren A. Henderson1,2
Christine Noel Duncan2,3,4
Susan E. Prockop2,3,4
Adrienne G. Randolph2,5
Barbara A. Degar2,3,4
Leslie E. Lehmann2,3,4
Susanne H.C. Baumeister2,3,4*- 1Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States
- 2Harvard Medical School, Boston, Massachusetts, United States
- 3Division of Hematology-Oncology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States
- 4Department of Pediatric Oncology, Dana–Farber Cancer Institute, Boston, Massachusetts, United States
- 5Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States
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Hemophagocytic lymphohistiocytosis (HLH) describes a severe, hyperinflammatory syndrome that can originate from diverse etiologies, often requiring critical care level management. Primary HLH, initially described in the 1940s, derives from genetic defects that result in uncontrolled immune activation. Although chemotherapy and immunosuppressive agents can temporarily quell inflammation, allogeneic hematopoietic cell transplantation (HCT) is the only curative option. In 2025, HCT is indicated for primary HLH and some etiologies of secondary HLH but remains challenging due to both disease and transplant-related inflammation. Additionally, new cellular therapy approaches to treat malignancy, such as chimeric antigen receptor T cells, can trigger a spectrum of hyperinflammatory complications. Herein, we review the pathophysiology, diagnosis, and evolving management approaches of primary and secondary HLH, ultimately informing our management of hyperinflammation in the setting of new cell therapies.
Keywords: Hemophagocytic lymphohistiocytosis, Primary HLH, Macrophage Activation Syndrome (MAS), Systemic juvenile idiopathic arthritis (sJIA), CAEBV, immune effector cell associated HLH-like syndrome (IEC-HS), pediatric critical care, Allogeneic Hematopoietic Cell Transplant
Received: 19 May 2025; Accepted: 31 Jul 2025.
Copyright: © 2025 Wobma, Henderson, Duncan, Prockop, Randolph, Degar, Lehmann and Baumeister. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Susanne H.C. Baumeister, Harvard Medical School, Boston, 02115, Massachusetts, United States
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