Case Report: Concurrent acute myeloid leukemia with KMT2A rearrangement and hemophagocytic lymphohistiocytosis: a diagnostic and therapeutic challenge

Introduction Simultaneous presentation of secondary hemophagocytic lymphohistiocytosis (HLH) with de novo acute myeloid leukemia (AML) is uncommon. KMT2A rearrangements, present in approximately 2–7% of de-novo AML, confer aggressive biology, and HLH at the initial diagnosis of KMT2A -rearranged AML is rare. Case-presentation A 47-year-old man presented with influenza-A infection, pancytopenia (WBC 1.08×10³/µL, hemoglobin 10.4 g/dL, platelets 147×10³/µL), acute kidney and hepatic dysfunction, disseminated intravascular coagulation, hypertriglyceridemia (517 mg/dL), hyperferritinemia (73, 776 µg/L), and splenomegaly meeting HLH-2004 criteria. Bone-marrow biopsy revealed 80% blasts with monocytic differentiation and hemophagocytosis, along with KMT2A rearrangement. Treatment with high-dose dexamethasone and 7 + 3 induction chemotherapy achieved MRD-negative complete remission. He received two cycles of high-dose cytarabine consolidation followed by allogeneic stem cell transplantation and remains in remission at 26 months. Conclusion To our knowledge, this is the first reported case of HLH occurring concurrently with de novo KMT2A-rearranged AML at initial diagnosis. This case highlights the importance of early recognition and concurrent management of HLH and KMT2A -r AML to prevent rapid clinical deterioration and achieve durable remission.