A Case of Chronic Lymphocytic Leukemia Complicated by Hemophagocytic Lymphohistiocytosis: Identifying the Aberrant Immune Response

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome that may complicate hematologic malignancies. HLH and malignancies have common clinical features, and HLH diagnostic criteria (HLH-2004/Hscore) were not validated in this specific population. We describe a case of a 72-year-old patient with a history of chronic lymphocytic leukemia stable for over 10 years who presented with fever and cytopenia. After excluding infectious etiologies and the progression of her disease, HLH was diagnosed. The patient was treated with etoposide, dexamethasone, intravenous immunoglobulin, and rituximab. Despite initial clinical improvement, the patient deteriorated and developed pulmonary aspergillosis and CNS involvement that reflected uncontrolled HLH. The patient died 45 days after her presentation. An unusual feature of this case was that HLH was not triggered by infection, disease transformation, or treatment. This case emphasizes the challenges of differentiating the development of overwhelming HLH from other complications associated with hematologic malignancy.

Keywords: CLL; HLH; chronic lymphocytic leukemia; fever; hemophagocytic lymphohistiocytosis; hemophagocytic syndrome; pancytopenia.

Figure 1.

Hemophagocytosis was present on the second bone marrow aspirate. Touch-preparation of the bone marrow biopsy showing phagocytosis by a macrophage of a lymphocyte (arrow) and platelet (arrowhead).

Figure 2.

Lung aspergillosis further complicated the clinical course. A computed tomography image demonstrating bilateral nodular infiltrates (arrowheads) and an evolving fungus ball with a halo sign at the periphery of the right upper lobe (arrow).

Figure 3.

Key features of the patient’s clinical course. Ferritin levels during the patient’s clinical course. The days of HLH-2004 criteria fulfillment and treatment administered are noted. HLH-94 refers to an 8-week protocol of etoposide and dexamethasone.