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Genetic marker linked to prolonged time on opioids after HSCT
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SALT LAKE CITY — Wild-type alleles found in the rs1042713 genotype of the beta-2 adrenergic receptor gene appeared to prolong time to optimal pain control and increase time on scheduled opioids among pediatric patients with mucositis following hematopoietic stem cell transplantation, according to study results presented at the BMT Tandem Meetings.
“Pain from mucositis is a major problem during the early posttransplant period in pediatric patients,” M. Christa Krupski, DO, MPH, from the division of bone marrow transplantation and immune deficiency at Cincinnati Children’s Hospital Medical Center, said during her presentation. “Adequate pain management is often delayed by trial and error of various agents and doses. Often by the time we have arrived at correct medicine and dose, the mucositis resolves on its own.”
Previous studies have shown polymorphisms in the beta-2 adrenergic receptor (ADRB2) gene were linked to both acute and chronic pain in different adult cohorts; however, this has not been evaluated in a pediatric population.
Krupski and colleagues created a panel of 46 single nucleotide polymorphisms in a set of candidate genes known to influence opioid effects. Researchers focused on ADRB2 and hypothesized that host ADRB2 polymorphisms would predict mucositis pain perception and lead to opioid requirement for pediatric patients who undergo HSCT.
Researchers genotyped 100 consecutive HSCT patients (median age, 9.9 years; range 0.5-32.8) using the panel of SNPs known to impact effects of opioids. Among the patients, 65% were male and 87% were white.
Researchers evaluated demographic and HSCT data, as well as detailed daily pain medication use from patient records.
Optimal pain control was defined as time after which no further opioid increases were required.
Seventy-six patients experienced mucositis at a median of 3 days (range, 2-17) post-HSCT and 63 patients required either scheduled IV opioid or patient-controlled analgesia.
Among the patients who required opioids, 55 had GA/GG (wild allele) and eight had minor allele (AA) for ADRB2.
Patients required a patient-controlled analgesia for a median of 16 days (range 1-32), and optimal pain control was achieved at a median of 8 days (range 1-23) after initiation of opioids.
Results showed the presence of at least one wild-type allele, rs1042713, for ADRB2 appeared associated with increased length of days on IV opioids. Among these patients, median days on IV opioids or patient-controlled analgesia was 17 days, compared with 8.5 days among patients with two minor alleles (P = .0012).
Patients with GA/GG genotype required more time to reach optimal pain control than patients with the AA genotype (median, 8 days vs. 1.5 days; P = .007).
The ADRB2 genotype was not associated with race; however, Krupski said it is important to keep race “in mind when adjusting opioids in these patients.”
Limitations of the study included small sample size, clinical limitations such as mucositis grading systems and use of pain scores, and the retrospective design.
“We have significant room for improvement in achieving efficient control of mucositis pain [among] patients undergoing HSCT. ... Prospective studies are needed to optimize safe and efficient pain control,” Krupski said. – by Melinda Stevens
Reference:
Krupski MC, et al. Abstract 33. Presented at: BMT Tandem Meetings; Feb. 21-25, 2018; Salt Lake City.
Disclosures: The authors report no relevant financial disclosures.