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.