Abstract P133

Recurrent Hemophagocytic Lymphohistiocytosis and Hepatic Failure in EBV-Associated Hodgkin Lymphoma

Introduction: Classic Hodgkin lymphoma (cHL) is a highly curable neoplasm. However, <30% of patients have a relapse/refractory disease. The concurrence of cHL and hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening event usually mediated by Epstein-Barr virus (EBV) with a dismal prognosis. We report a clinical case of 42 year-old male that debuted with HLH related to EBV(+) cHL.

Case presentation: A 42-year-old male was admitted with B symptoms and cytopenias. Positron emission tomography-computed tomography (PET/CT) showed nodal and extranodal hypermetabolic activity. A high plasma EBV viral load was detected. The patient experienced a rapid clinical deterioration with multiorgan failure (renal and hepatic failure). The clinical presentation was consistent with HLH confirmed by bone marrow aspirate. The lymph node biopsy demonstrated EBV(+) cHL. Thus, treatment with ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) for 6 cycles was started. At the end of treatment evaluation, patient had a second event of HLH in the context of lymphoma progression. Then, Br-ESHAP (Brentuximab vedotin, etoposide, methylprednisolone, cytarabine and cisplatin) was initiated with transient improvement. Due to persistent HLH event, anakinra and high dose of steroids was added to therapy. After a fourth HLH episode, third-line treatment with nivolumab was started. Remarkable clinical improvement and resolution of EBV reactivation were observed with this treatment. The HLH recurrences linked to EBV reactivation prompted evaluation by a multidisciplinary team due to suspicion of an underlying primary immunodeficiency. Although the genetic panel (NGS) did not identify known causal mutations, the committee dismissed autologous transplantation and ruled out the use of an HLA-identical familial donor to avoid the potential transmission of an unknown genetic defect. Finally, the patient underwent allogeneic hematopoietic stem cell transplantation from an unrelated donor (9/10). Last evaluation, confirmed complete remission with full donor chimerism.

Conclusion: In this patient, relapsed EBV(+) cHL associated with HLH, nivolumab offered a targeted and highly effective treatment which allowed HLH resolution and cleared viremia, serving as a bridge to allogeneic transplantation. Beyond suspicion of immunodeficiency and in absence of molecular genetic characterization, selection of an unrelated donor is recommended to avoid familial susceptibility.