From Remission to Complication: Hemophagocytic Lymphohistiocytosis and Avascular Necrosis During Brentuximab Therapy in Hodgkin Lymphoma

Relapsed and refractory classical Hodgkin lymphoma (HL) remains a significant clinical challenge despite advances in salvage chemotherapy and autologous stem cell transplantation (ASCT).We report the case of a 37-year-old man diagnosed with stage II classical HL and treated at the university hospital in Alexandria, Egypt, who initially achieved complete remission following doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy but relapsed within six months.He subsequently received salvage dexamethasone, high-dose cytarabine, and cisplatin (DHAP) chemotherapy followed by ASCT, achieving remission.A second relapse occurred, and the patient was treated with brentuximab vedotin in combination with bendamustine, resulting in complete metabolic remission.During maintenance brentuximab therapy, he developed recurrent low-grade fever, pancytopenia, and progressive left hip pain.Imaging revealed a fluorodeoxyglucose (FDG)-avid osteolytic lesion in the femoral head without evidence of nodal disease, raising concern for relapse.However, bone marrow biopsy demonstrated hemophagocytosis without lymphoma infiltration.Laboratory evaluation showed markedly elevated ferritin and triglyceride levels, supporting the diagnosis of hemophagocytic lymphohistiocytosis (HLH).Brentuximab therapy was discontinued, and corticosteroids and cyclosporine were administered, followed by gradual clinical and hematologic improvement.Subsequent magnetic resonance imaging (MRI) revealed avascular necrosis of the femoral head with multiple bone infarcts.Follow-up evaluation later confirmed disease relapse.This case highlights the diagnostic complexity of distinguishing disease progression from treatment-related complications in refractory classical HL and underscores the importance of early recognition of HLH and avascular necrosis as rare but serious adverse events associated with targeted and immunomodulatory therapies.Prompt diagnosis and appropriate management are essential to optimize patient outcomes.