Case Description
A 78-year-old-man with CKD and congenital solitary kidney was diagnosed with CLL 15 years prior. The Rai classification was intermediate 1, the Binet classification was A, and watchful waiting was adapted. However, lymphocytosis and lymph node enlargement progressed four years after his first visit; therefore, he was prescribed oral fludarabine treatment. Four years after the oral fludarabine treatment, lymph node enlargement progressed again and hence he was prescribed bendamustine with rituximab (BR) therapy. Treatment response was good, but because severe neutropenia occurred, BR therapy was stopped at two cycles. Two years after the BR therapy, CLL progressed again, and BR treatment was administered again for two cycles. Two years after the last BR treatment, lymphocytosis progressed again; therefore, ibrutinib, an inhibitor of Bruton’s tyrosine kinase and an effective agent for CLL, was initiated and administered for two years. However, lymphocytosis and lymph node enlargement gradually progressed, and he was admitted to our hospital.
Laboratory data on the admission day revealed severe lymphocytosis, severely impaired renal function, and mildly increased liver enzymes (Table 1). The serum creatinine level was 2.7 mg/dL, and the estimated GFR from creatinine was 18.7 mL/min/1.73 m2. He was diagnosed as having a relapse of CLL and complications of severe CKD (stage 4, GFR<30mL/min). Computed tomography (CT) revealed systemic lymphadenopathy and splenomegaly. Because of severe lymphocytosis, systemic lymphadenopathy, splenomegaly, and severe CKD from congenital solitary kidney, the risk of TLS was considered extremely high; therefore, oral cyclophosphamide and prednisolone with four cycles of rituximab were administered to reduce tumor burden before venetoclax therapy. The lymphocyte count reduced to 15000 cells/μL, and lymphadenopathy and splenomegaly were ameliorated. After debulking of the tumor, 20 mg/day venetoclax was initiated, along with intensive prevention of TLS involving hydration, 60 mg/day febuxostat, and 7.5 mg/body rasburicase. This is because we assessed that the risk of TLS was still high because of the complications of severe CKD. Strict monitoring of laboratory data at 4, 8, 12, and 24 hours after the start of venetoclax (Figure 1) on the first administration day revealed a slight increase in the lactate dehydrogenase level with no laboratory abnormality, which met the criteria for TLS diagnosis. Subsequently, the venetoclax dose was increased weekly to 50 mg/day and 100 mg/day without TLS, but catheter-induced blood stream infection occurred, and venetoclax treatment was stopped for a week. After catheter exchange and antibiotic administration, venetoclax treatment was restarted at a dose of 100 mg/day and increased weekly to 200 mg/day and 400 mg/day without TLS. Lymphocytosis and soluble interleukin-2 receptor immediately decreased to the normal range. We observed that response to venetoclax treatment was quite good. After venetcoclax reached maintenance dose, he was discharged on day 113 post-admission, and received additional rituximab as outpatient (clinical course during admission is summarized in Figure 2). We told the importance of this case to patient and obtained informed consent to publish.