Introduction
Tumor lysis syndrome (TLS) is a life-threatening condition caused by the
rapid destruction of malignant cells leading to leading to imbalances in
various electrolytes, and posing risks such as acute kidney injury
(AKI), arrhythmia, seizures, and potentially fatal outcomes if not
managed appropriately [1]. TLS primarily occurs in
highly-proliferative hematological malignancies such as acute leukemia
and high-grade non-hodgkin lymphomas (NHL), while its occurrence in
solid tumors is less common [2]. TLS is burdened with significant
morbidity and mortality, and may occur spontaneously and/or shortly
after treatment initiation [3]. Even though TLS can lead to fatal
outcome, there have been limited studies focused on this condition.
TLS contributes to the formation of uric acid crystals and/or calcium
phosphate salts, which deposit in renal tubules, resulting in acute
obstruction and kidney failure [4]. The precise incidence of TLS
remains uncertain, with historical reports indicating rates as high as
48%, including 6% clinically significant TLS in NHL [5]. However,
recent retrospective studies including various highly-proliferative
onco-hematological malignancies reported TLS occurrence rates ranging
from 5% to 16% [3,6,7]. In approximately one-quarter of cases,
hemodialysis and intensive care unit interventions were required, while
TLS-related mortality ranged from 14% to 21% [3,7,8]. Recognized
clinical risk factors for TLS development include high tumor burden and
proliferation index, increased sensitivity to chemotherapy, elevated
white blood cell count and preexisting renal impairment of the patient
[1,9]. The estimated risk of TLS \soutstands at is 15% for
Burkitt lymphoma (BL) and 6% for diffuse large B-cell lymphoma (DLBCL)
[1].
Early risk stratification based on tumor burden evaluation is required
to efficiently prevent TLS. Intravenous hyperhydration along with
urate-lowering treatments such as xanthine oxydase inhibitors or
uricolytic agents like the recombinant urate oxidase enzyme rasburicase
have shown significant reduction in TLS incidence [8–11].
Additionally, preemptive debulking approaches, involving steroids and/or
low-dose chemotherapy prophase, as well as ramp-up dose schedule are
used dependent on malignant condition and clinical assessment of tumor
burden [7, 11-13].
Rituximab, an anti-CD20 monoclonal antibody is commonly used in
combination with cytotoxic chemotherapy for the treatment of B-cell
malignancies [14,15]. Early studies used fractionated rituximab as a
means to mitigate the risk of infusion reactions and TLS during the
initial administration in low-grade B-cell malignancies, although this
strategy is no longer recommended [16-19].
In this study, we present a retrospective analysis of a single-center
experience on the use of fractionated rituximab as a debulking strategy
in 94 patients with B-cell malignancies at high-risk for TLS over a
ten-year period.