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Venetoclax rapidly induces apoptosis and carries a boxed warning for TLS, particularly in patients with high absolute lymphocyte counts, bulky nodes, or impaired renal function. Evidence-based mitigation uses a weekly dose-ramp schedule to gradually debulk disease, combined with pre- and post-dose hydration (oral/IV), uric acid lowering (allopurinol for most; rasburicase for very high risk or elevated baseline uric acid), and electrolyte monitoring. High-risk initiations warrant inpatient observation with labs at ~6–8 hours and 24 hours after each new dose; intermediate risk may be outpatient with intensive monitoring if reliable. Beginning at full dose (Option A) is unsafe. Assuming oral therapy is low risk (Option C) ignores pharmacology. Diuretics alone (Option D) do not prevent urate/phosphate precipitation or hyperkalemia. The APRN operationalizes risk stratification, TLS ordersets, patient education (red flags), and clear criteria to hold or repeat a dose escalation step if labs worsen, working closely with pharmacy and inpatient teams.