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This report aims to highlight the rare occurrence of HLH during ibrutinib treatment in a patient with CLL.

January 21, 2026Medicine0 citationsOpen Access

A case report of hemophagocytic lymphohistiocytosis occurring during ibrutinib chemotherapy with a literature review

XHXiaonan HouShandong First Medical University MWManzhi WangChangsha Central Hospital SMShengchao MiaoShandong First Medical University

Key Points

This report aims to highlight the rare occurrence of HLH during ibrutinib treatment in a patient with CLL.
Documented patient history and clinical presentation of symptoms
Performed bone marrow biopsy for diagnosis confirmation
Initiated HLH-94 treatment protocol including etoposide and dexamethasone
Conducted literature review on the association between ibrutinib and HLH
Patient developed HLH five months after starting ibrutinib treatment.
Reported complications included fungemia and a massive cerebral infarction.
Patient's condition deteriorated, leading to treatment withdrawal and eventual death.

Abstract

Rationale: Ibrutinib, a Bruton tyrosine kinase inhibitor, is widely used in chronic lymphocytic leukemia (CLL). Its association with secondary hemophagocytic lymphohistiocytosis (HLH) is exceedingly rare but potentially fatal. Patient concerns: A 59-year-old male with CLL presented with recurrent fever and progressive splenomegaly. Diagnoses: Bone marrow biopsy confirmed CLL. Five months after ibrutinib (420 mg/day) initiation, progressive pancytopenia, hyperferritinemia, and hemophagocytosis on repeat marrow aspirate established HLH diagnosis. Interventions: HLH-94 protocol (etoposide + dexamethasone) was initiated. Outcomes: The patient developed fungemia followed by massive cerebral infarction. Treatment was withdrawn due to deterioration, resulting in death. Lessons: Ibrutinib may trigger HLH via immune dysregulation. Early recognition through vigilant monitoring of cytopenias, ferritin, and marrow hemophagocytosis is critical to improve survival.

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