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• W2589799544 abstract "Mucositis pain after hematopoietic cell transplantation (HCT) is a major burden on quality of life for pediatric patients. Adequate pain management is often delayed by trial and error of various agents and doses. We hypothesized that host genetic polymorphisms will predict pain perception, opioid efficacy, and opioid-induced adverse effects in HCT patients. We tested our hypothesis by genotyping 98 consecutive HCT patients (5/2013 – 10/2014) using pre-HCT samples. A panel of 46 single nucleotide polymorphisms (SNPs) in a set of candidate genes known to influence opioid effects was used. We collected demographic and HCT data, along with detailed daily pain medication use from patient records. Our cohort included 64% male and 85% Caucasian patients at a median age of 9.9 years (range .5-32.8). Seventy-six patients (78%) experienced mucositis a median of 3 days (range –2 to +17) post-HCT; 58 (76%) of these required PCA, and 5 (7%) used scheduled IV opioids. We defined optimal pain control as time after which no further opioid increases were required. Our patients reached optimal pain control a median of 7 days (range 0-22) after opioid initiation. At optimal pain control, median peak morphine-equivalent dose was 1.5 mg/kg (range .2-15.7). Patients were on a PCA for a median of 16 days (range 1-32). Eighteen patients (29%) on IV opioids required ≥1 medication change due to lack of efficacy. Thirty-two patients on IV opioids (51%) experienced ≥1 side effect (pruritus, over-sedation, excessive nausea/emesis). Twenty patients (32%) required opioid change due to toxicity. We found a strong correlation between common uridine diphosphate glucuronosyl transferase (UGT) 2B polymorphisms and race. The SNPs rs7668258 and rs7439366demonstrated perfect linkage, and variants of UGT2B were present in 75% of Caucasians, but only 31% of non-Caucasians (P = .0011). Patients with wild-type UGT2B alleles spent more total days on IV opioids compared with those with variant alleles (P = .0299). This finding supports our observation that non-Caucasians had a higher incidence of mucositis than Caucasians (100% vs. 74%; P = .0366). Non-Caucasians had more pain with mucositis; 92% required scheduled IV opioids, compared to 60% of Caucasians (P = .029). We also found that those with rs4633 variants in catechol-O-methyltransferase (COMT) required more days to optimal pain control compared to wild type (P = .0287), confirming increased pain sensitivity associated with this genotype, irrespective of race. We did not find any association between any SNPs and opioid toxicity, as has been reported in different clinical contexts. Our data suggest that prospective genotyping will improve achievement of optimal pain control in all pediatric patients undergoing HCT. If genotyping is not feasible, paying particular attention to pain control in non-Caucasian patients will allow timely and efficacious pain management." @default.
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• W2589799544 date "2017-03-01" @default.
• W2589799544 modified "2023-09-23" @default.
• W2589799544 title "Prediction of Opioid Requirement for Mucositis By Genotype in Children Undergoing Hematopoietic Cell Transplantation" @default.
• W2589799544 doi "https://doi.org/10.1016/j.bbmt.2016.12.103" @default.
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