Abstract Introduction Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome that can closely mimic septic shock, particularly in adults with cancer or immune dysregulation. HLH has been reported as a rare complication of chemotherapy and immune checkpoint inhibitors (ICIs), most often in solid tumors (e.g., melanoma, lung cancer), with fewer reports in lymphoma. Delayed-onset HLH after completion of chemo-immunotherapy is uncommon and clinically important because it can present with sepsis-like physiology and lead to diagnostic delay. We report a case of HLH occurring three months after completion of doxorubicin, vinblastine, and dacarbazine (AVD) plus nivolumab for classical Hodgkin lymphoma, initially manifesting as refractory shock. Case Report A 64-year-old woman with classical Hodgkin lymphoma in complete remission (last AVD plus nivolumab July 2025) presented with weakness, diarrhea, and thrombocytopenia (platelets 17 × 109/L). She developed fluid-refractory hypotension and was transferred to the intensive care unit for presumed septic shock, requiring norepinephrine (up to 0.2 µg/kg/min) for three days, without need for mechanical ventilation or renal replacement therapy. Blood and urine cultures were negative; respiratory PCR and CT chest/abdomen/pelvis showed no infectious source. Laboratory testing revealed ferritin 18,000 ng/mL, soluble interleukin-2 receptor (sIL-2R) 25,000 U/mL, elevated triglycerides, and severely low fibrinogen 100 mg/dL. She met the HLH-2004 criteria, exhibiting hyperferritinemia, cytopenias, hypofibrinogenemia, hypertriglyceridemia, and fever. Furthermore, her HScore was 228 (reference range of 0-300), indicating a very high probability of HLH. Bone marrow biopsy demonstrated trilineage hematopoiesis with hemophagocytosis, confirming the diagnosis. High-dose dexamethasone and etoposide, initiated per the HLH-94 protocol, led to hemodynamic recovery with vasopressors weaned by ICU Day 4 and improved cytopenias, with platelets rising to 71 ×109/L by discharge. After a four-week hospitalization, she was discharged home with resolving cytopenias. At outpatient follow-up two days later and in subsequent visits, she remained in remission. Discussion Immune checkpoint inhibitor-associated HLH is rare and typically occurs in those with solid tumors. Delayed presentations after treatment are especially uncommon in hematologic malignancies. The confluence of Hodgkin lymphoma in remission, prior nivolumab exposure, and delayed HLH onset makes this case noteworthy. In adults with refractory shock after recent chemo-immunotherapy, early recognition of HLH is critical. Prompt evaluation including ferritin and sIL-2R measurement, HScore calculation, and bone marrow examination should be pursued. Timely initiation of HLH-directed therapy may improve survival and overall outcomes. This abstract is funded by: None
Boodhun et al. (2026) studied this question.