Development of a human herpesvirus 8-negative effusion-based lymphoma during treatment with dasatinib for chronic myeloid leukemia

Abstract

Primary effusion lymphoma (PEL) is defined as human herpesvirus 8 (HHV8)-positive effusion-based lymphoma (EBL) according to the fourth version of the World Health Organization (WHO) classification. However, PEL-like disease has also been reported and is referred to as "HHV8unrelated PEL-like lymphoma" or "HHV8-negative EBL." Most of the EBL cases reported in East Asia are not related to HHV8; in fact, 17 of 25 Taiwanese patients and 64 of 69 Japanese patients were negative for HHV8. 1,2 Approximately half of HHV8-negative EBL patients had underlying medical conditions leading to fluid overload, including cirrhosis and cardiac complications. 3,4 Immunosenescence may also play a role in the development of HHV8-negative EBL in the elderly. 1,2 Dasatinib, a tyrosine-kinase inhibitor (TKI) used for the treatment of chronic myeloid leukemia (CML), frequently induces pleural effusion (PE) (28-33%), 5 which is caused by lymphocyte-predominant exudates. 6 To date, six cases of HHV8-negative EBL developed during dasatinib treatment, have been reported. [7][8][9][10][11] Here, we report a rare case of HHV8-negative EBL that developed during long-lasting dasatinib-induced PE. CASE REPORTAn 85-year-old man was diagnosed with CML in May 2016. He was treated with a TKI imatinib, which was discontinued due to facial and lower limb edema and appetite loss. In September 2016, imatinib was replaced by bosutinib, but treatment was discontinued because of the onset of diarrhea. As a third-line TKI, treatment with dasatinib was initiated in January 2017 with an initial dose of 50 mg/day. As bilateral PE developed one month later, the patient continued to receive a reduced dose of dasatinib (20 mg/day) with furosemide. A profound molecular response (International Scale (IS), 0.0055%) was achieved in August 2017.He complained of increasing dyspnea on exertion in October 2020. Chest radiography and computed tomography (CT) revealed bilateral PE and pericardial effusion (Figure 1, A). Furosemide and tolvaptan were administered under the diagnosis of congestive heart failure. Dasatinib