Secondary Hemophagocytic Lymphohistiocytosis Syndrome Developing in a Patient With Chronic Lymphocytic Leukemia Under a Long-term Ibrutinib Therapy: A Case Report and Literature Review

Abstract

Secondary hemophagocytic lymphohistiocytosis (HLH) syndrome, a fatal disorder characterized by NK/T-cell deficiency, cytokine storm, and organ damage, is rare in chronic lymphocytic leukemia (CLL). Ibrutinib, the first generation of irreversible Bruton's tyrosine kinase inhibitor, has been the first-line therapy for CLL. As an off-target effect, it can also block IL-2 inducible T-cell kinase (ITK), which is essential in maintaining normal NK and T-cell functions. Up to now, 4 cases reported secondary HLH developed in CLL patients shortly after ibrutinib therapy, which indicated ibrutinib might be associated with HLH via NK/T cell damage as a result of ITK inhibition. We herein report the first case describing EBV-driven HLH developed in a CLL patient under long-term ibrutinib monotherapy (4 year), also showing concurrent NK and T cell deficiency. Therefore, the relationship between the long-term use of ibrutinib and the pathophysiology of HLH, as well as the mediating role of NK/T cell disorder caused by ITK blockade therein, deserves attention and further studies.