Hemophagocytic Lymphohistiocytosis with onset of mental and behavioral disorders following allogeneic hematopoietic stem cell transplantation: A case report

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a rare but highly fatal complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT), with central nervous system involvement (CNS-HLH) being exceptionally uncommon in adults and posing significant diagnostic challenges. This report details a 24-year-old male with acute myeloid leukemia (AML-M5) who developed CNS-HLH on +50 day after haploidentical allo-HSCT. The patient achieved complete donor chimerism post-transplant with no active infections but subsequently presented with acute neuropsychiatric symptoms, including short-term memory impairment, hypersomnia, reduced verbal output, and psychomotor retardation, rapidly progressing to coma. Laboratory findings revealed pancytopenia, hyperferritinemia (4301 μg/L), hypertriglyceridemia, and elevated CD8⁺ T lymphocytes (58 %). Cerebrospinal fluid analysis showed increased pressure (220 mmH₂O) and markedly elevated protein (1350.3 mg/L), while cranial MRI demonstrated bilateral hippocampal and amygdaloid hyperintensities. Bone marrow examination confirmed hemophagocytosis, fulfilling the HLH-2004 criteria and modified post-HSCT HLH diagnostic criteria for secondary HLH. Despite aggressive interventions—high-dose methylprednisolone, intravenous immunoglobulin, plasma exchange, and ruxolitinib combined with intrathecal therapy—the patient remained comatose and succumbed to multi-organ failure. This case underscores the unique clinical trajectory of post-HSCT CNS-HLH, where neuropsychiatric manifestations precede classical hematologic abnormalities and conventional immunosuppressive therapies exhibit limited efficacy. The findings emphasize the imperative for heightened clinical suspicion of HLH in transplant recipients with unexplained neurological deterioration accompanied by progressive cytopenias and biomarker derangements. Furthermore, this report highlights the urgent need for optimized early diagnostic strategies and targeted therapeutic approaches for CNS-HLH. The case provides critical insights into the clinical management and mechanistic understanding of post-transplant HLH.