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Oral cryotherapy (ice chips or cold water rinses) during and immediately after melphalan infusion reduces mucosal blood flow, limiting drug delivery to oral tissues and thereby decreasing the incidence and severity of mucositis. This low-cost, well-tolerated intervention has strong support in conditioning regimens that include short–half-life agents like melphalan. Chlorhexidine rinses (Option A) do not prevent chemotherapy-induced mucositis and may worsen irritation. Routine prophylactic antibiotics (Option C) are not indicated solely for mucositis prevention and contribute to antimicrobial resistance. Sucralfate (Option D) has not shown consistent benefit in prevention. APRNs should implement a comprehensive oral care protocol—baseline dental evaluation, soft-bristle brushing, saline/baking soda rinses, avoidance of irritants, pain management, and nutritional support—while educating patients on early symptom reporting. For severe cases, consider analgesic strategies (topical and systemic), parenteral nutrition if needed, and evaluation for palifermin in select transplant settings per institutional policy.