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Treatment of neuroblastoma with targeted immunotherapy using chimeric anti-GD2 monoclonal antibodies (ch14.18) is associated with significant pain requiring management with a high-dose opioid infusion. We present a case series of six children, for whom dexmedetomidine and hydromorphone infusions safely and effectively reduced the pain of ch14.18 therapy in the oncology ward setting.The ch14.18 infusion is administered for ≥10 hr over four consecutive days in each of 5 cycles. Hydromorphone (2–8 mcg.kg−1.hr−1) and dexmedetomidine (0.1–0.6 mcg.kg−1.hr−1) infusions were commenced 1 hr before starting ch14.18 immunotherapy and titrated to optimal clinical effect. One hour after stopping the ch14.18 infusion, dexmedetomidine was discontinued and hydromorphone weaned as tolerated. This strategy was supervised by the Acute Pain Service with strict monitoring and nursing policies. Patient charts were reviewed for evidence of side effects and quality of analgesia.Data from six patients, with median (range) age of 3.5 (2–12) years are reported. Median (range) utilization of hydromorphone was 2.9 (2.0–4.7) mcg.kg−1.hr−1, and of dexmedetomidine was 0.17 (0.10–0.20) mcg.kg−1.hr−1. A drop in mean arterial pressure ≥30% below baseline was identified during 30% of treatment days, but only prompted interrupting or reducing the ch14.18 infusion on 7% of treatment days; only one episode of grade 3 hypotension was recorded during this series. Hypoxemia occurred during 8% and bradycardia during 4% of treatment days.Dexmedetomidine infusion may be an effective and safe pain management adjunct to opioid therapy for the pain of ch14.18 infusion. Pediatr Blood Cancer 2015;62:29–34. © 2014 Wiley Periodicals, Inc.