C50-26 Epstein-Barr Virus (EBV)-associated Severe Aplastic Anemia Unmasked by a Cytokine Storm: A Distinct and Devastating Presentation

EBV reactivation can lead to rare instances of severe aplastic anemia (SAA). The virus activates cytotoxic lymphocytes, which invade the bone marrow and subsequently damage the hematopoietic functionality. Early recognition is imperative to prevent these complications and to improve clinical practice.Here, we present a case of reactivated EBV-associated aplastic anemia and cytokine storm. A 65-year-old male with a history of chronic lymphocytic leukemia (CLL) in remission since 2017 presented with four months of severe pancytopenia, recurrent fever, lymphadenopathy, and behavioral disturbances. He had received multiple courses of antimicrobial and antifungal therapy, as well as granulocyte colony-stimulating factor, with minimal improvement.On admission, he was hypotensive and required initiation of vasopressor support. Laboratory evaluation showed profound pancytopenia (WBC 1.3 K/µL, platelets 10 K/µL, Hgb 7.0 g/dL) and elevated transaminases. CT of the chest, abdomen, and pelvis revealed mediastinal and abdominal lymphadenopathy with splenomegaly. Peripheral smear showed no blasts. Bone marrow biopsy demonstrated marked hypocellularity (≈5% hematopoiesis). Flow cytometry was negative for lymphoproliferative disorder. Immunoglobulin G was markedly low.Ferritin was 34,000 ng/mL, triglycerides were elevated, and soluble IL-2 receptor was markedly increased (∼30,000 pg/mL). CD4/CD8 ratio was 0.4, with an absolute CD4 count of 24. EBV PCR was positive (160,308 copies/mL). These findings supported a diagnosis of EBV reactivation with severe aplastic anemia and cytokine storm.Despite aggressive medical therapy including high dose steroids, the patient’s condition continued to worsen and rapidly progressed to multiorgan failure, requiring life-sustaining measures. The patient passed away after 7 days of escalated therapy. Here, we illustrate a case of EBV-associated severe aplastic anemia during reactivation, eventually progressing to cytokine storm, multiorgan failure, and subsequent death. There was a presumptive clinical diagnosis leaning toward recurrent CLL, given the presence of severe pancytopenia and lymphadenopathy, diverting attention from alternative clinical possibilities. However, bone marrow studies ruled this out. There was no testing for EBV prior to the latest Hospitalization, which raises a pivotal question of whether earlier bone marrow evaluation and viral testing could have changed the tragic trajectory of the clinical course in our patient.EBV-associated severe aplastic anemia carries a poor prognosis, with mortality exceeding 50%, particularly in reactivation cases presenting with pancytopenia. The overall outcome remains poor, compounded by the absence of robust clinical practice guidelines. Physicians should maintain a high index of suspicion for EBV-associated aplastic anemia, as early recognition is crucial to initiating timely interventions such as hematopoietic stem cell transplantation.