Secondary Hemophagocytic Syndrome Associated with Richter’s Transformation in Chronic Lymphocytic Leukemia

Hemophagocytic syndrome (HPS) is an extremely rare condition arising from the overactivation of one’s own immune system. It results in excessive inflammation and tissue destruction. Prompt initiation of treatment is warranted in either scenario in order to decrease mortality. Most cases are triggered by infectious agents, malignancy, or drugs. We describe the first case of a CLL patient presenting with HPS due to acquisition of EBV-related large cell lymphoma in the setting of profound immunodeficiency. 1. Background Hemophagocytic syndrome (HPS) is an extremely rare but potentially fatal hyperinflammatory condition arising from the overactivation of one’s own immune system. It can be classified as either primary or secondary [1, 2]. Primary HPS, also known as familial hemophagocytic lymphohistiocytosis (FHL), is an autosomal recessive disorder caused by the inheritance of gene mutations producing defective regulatory proteins responsible for the cytolysis of abnormal immune cells [2, 3]. Secondary HPS is caused by strong self-immunologic activation that is mostly not hereditary but arises due to triggers in the setting of conditions such as autoimmune diseases, immunodeficiency, underlying malignancy or disseminated infections from viruses, fungi, or bacteria [2, 4, 5]. However, approximately 15% of secondary HPS patients have an underlying hereditary predisposition to develop HPS. Either form of HPS results in excessive inflammation and tissue destruction. Prompt initiation of treatment is warranted in either scenario in order to decrease mortality [1]. On the other hand, chronic lymphocytic leukemia (CLL) is the most common leukemia in the Western world with a heterogeneous and mostly prolonged disease course [6, 7]. CLL patients are immunodeficient to a degree, with a significant proportion being hypogammaglobulinemic [8, 9]. Furthermore, profound defects of cell-mediated immunity can more readily occur in those treated with purine analogues [10]. Secondary HPS has been sparsely reported in association with CLL. However, most cases were triggered by an infective agent, such as EBV, histoplasmosis, or H1N1 influenza [5, 11–14], by the chemotherapeutic drugs used in the treatment of CLL such as fludarabine or rituximab [4] or by the direct progression of CLL itself [15, 16]. To date there have been no cases in the literature reporting a CLL patient presenting with a secondary HPS due to acquisition of EBV related large cell lymphoma in the setting of profound immunodeficiency as described in this case report. 2. Case Presentation A 57-year-old