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.