Tumor Lysis Syndrome Risk in Burkitt Lymphoma Versus Mantle Cell Lymphoma During Alkylating Therapy: A Propensity-Matched TriNetX Comparative Outcome Analysis.

Background Tumor lysis syndrome (TLS) is a preventable oncologic emergency that can rapidly progress to acute kidney injury, malignant arrhythmias, seizures, and death. Because key prevention decisions (prophylaxis intensity, monitoring frequency, and inpatient versus outpatient initiation) are made at the start of therapy, clinically useful risk estimates must separate intrinsic disease risk from regimen-driven risk. However, cross-histology TLS comparisons are frequently confounded by systematic differences in chemotherapy composition and intensity. We therefore evaluated whether Burkitt lymphoma retains a higher TLS risk than mantle cell lymphoma (MCL) under a treatment-restricted framework anchored to shared alkylating exposure, with the goal of generating practical clinical insight for early TLS risk recognition, prevention, and monitoring in real-world practice, including urgent and emergency care settings. Methods We performed a retrospective cohort study using the TriNetX Global Collaborative Network, a federated real-world electronic health record research platform. Two cohorts were constructed (Burkitt lymphoma and MCL) and restricted to patients with exposure to cyclophosphamide or ifosfamide. Identical exclusions were applied to both cohorts for anthracyclines (doxorubicin, daunorubicin, epirubicin, idarubicin, and valrubicin), immune checkpoint inhibitors (nivolumab and pembrolizumab), and lymphoma coded as "in remission." Outcomes were assessed beginning one day after cohort entry (index event).  The primary outcome was TLS (ICD-10-CM E88.3). Propensity score matching was performed 1:1. Time-to-event analyses used Kaplan-Meier methods with log-rank testing.  Results After propensity score matching, 290 patients were included in each cohort (290 matched pairs). TLS occurred in 10.0% of the Burkitt cohort (29/290) compared with 5.5% of the mantle cell cohort (16/290), corresponding to an absolute risk difference of 4.5% (95% CI 0.1-8.8%; p = 0.044). On a relative scale, Burkitt lymphoma was associated with higher TLS risk, with a risk ratio of 1.813 (95% CI 1.006-3.264) and an odds ratio of 1.903 (95% CI 1.010-3.585), indicating a consistent direction and magnitude of effect across measures. Time-to-event analyses were concordant with the risk-based estimates: Kaplan-Meier analysis demonstrated shorter TLS-free survival in the Burkitt cohort (log-rank p = 0.034; HR 1.915, 95% CI 1.039-3.527). Median TLS-free survival was not reached in either cohort within available follow-up.  Conclusions In this propensity-matched real-world cohort restricted to cyclophosphamide/ifosfamide exposure and excluding anthracyclines and immune checkpoint inhibitors, Burkitt lymphoma was associated with higher TLS incidence and shorter TLS-free survival compared with MCL. These findings support classifying Burkitt lymphoma as a higher-risk phenotype at treatment initiation and adopting more intensive TLS prevention and monitoring strategies (particularly proactive hydration and closer biochemical surveillance) with escalation of urate-lowering therapy as indicated, consistent with established TLS risk frameworks.