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

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 Treatment was withdrawn due to deterioration, resulting in death.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.