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ORLANDO, FL—A pilot study to determine the burden of mucositis in pediatric patients undergoing hematopoietic stem cell transplant (HSCT) showed that more than 50% of patients required a change in their opioids either for toxicity or lack of efficacy.
Investigators also observed that patients’ genotypes were associated with time to optimal pain control, although this needs to be defined more clearly in larger prospective studies.
“Pain from mucositis is a major problem during the early post-transplant period in pediatric patients,” said M. Christa Krupski, DO, of Cincinnati Children’s Hospital Medical Center in Ohio.
The pain frequently requires intravenous (IV) pain medication, but adequate pain management is often delayed by the trial and error of finding the right agent or the right dose, Dr Krupski added.
She and her colleagues tried to find predictors of mucositis that would help optimize pain control and minimize adverse effects of pain medication.
Dr Krupski presented the group’s findings at the 2017 BMT Tandem Meetings as abstract 50*.
Based on the investigators’ previous experience using a pain chip, they hypothesized that host genetic polymorphisms would predict perception of mucositis pain, opioid efficacy, and opioid-induced adverse effects in pediatric patients undergoing HSCT.
The pain chip was comprised of a panel of 46 single-nucleotide polymorphisms (SNPs) in a set of candidate genes known to influence opioid effect.
Study design
In this single-institution, retrospective pilot study, investigators genotyped 100 consecutive HSCT patients using pre-transplant samples.
The team collected demographic and transplant data, information on the utilization of pain medication, and mucositis data according to the standard CTCAE guidelines.
“And it must be noted,” Dr Krupski said, “that many of our patients required total parenteral nutrition during the transplant process, which automatically made them a grade 3 for mucositis.”
The investigators assessed pain using 2 scales, the Face, Legs, Activity, Cry, Consolability (FLACC) Scale, which is an objective measurement, and the more subjective Numeric Rating Scores (NRS).
Demographics
Patients were a median age of 9.9 years (range, 0.5–32.8), 65% were male, 87% were Caucasian, and 13% non-Caucasian.
The main indications for transplant were malignancy (45%), immune deficiency/dysregulation (30%), and bone marrow failure syndrome (19%).
More than two-thirds (68%) of patients had received a myeloablative conditioning regimen.
Results—mucositis
Seventy-six patients experienced mucositis, three-quarters of whom (78%) had received a myeloablative conditioning regimen.
The majority of patients (57%) had severe mucositis, which developed a median of 3 days after transplant (range, -2 to 17).
Regarding treatment, 13 (17%) had medication as needed or no medication, 5 (7%) had scheduled IV opioid, and 58 (76%) had patient-controlled analgesia (PCA).
For analysis purposes, the investigators grouped together the scheduled IV opioid and PCA treatment groups.
Results—opioid efficacy
The opioid efficacy analysis was based on 63 patients.
Time to optimal pain control was a median of 7 days (range, 0–22), and the morphine dose at the time of optimal pain control was a median of 1.5 mg/kg (range, 0.2–15.7).
“You will note, though, the wide inter-patient variability,” Dr Krupski pointed out, “with some of our patients immediately achieving optimal pain control the day the medication was started and others taking over 3 weeks to reach optimal pain control.”
Investigators observed similar inter-patient variability in morphine equivalent use at the time of optimal pain control and total morphine equivalent use.
The total time patients were on PCA was a median of 16 days (range, 1–32), and the median total morphine equivalent use was 0.99 mg/kg/day (range, 0.10–8.07).
“Most interesting, though, was that 18 patients, or nearly one-third of the patients requiring IV opioids, required a change in this opioid due to poor efficacy,” Dr Krupski said.
Results—opioid toxicity
Thirty-two (51%) patients experienced at least 1 adverse effect from their pain medication.
Specific toxicities, based on 32 patients, included pruritus (53%), sedation (16%), and nausea/vomiting (9%). Six patients (19%) had more than one adverse event.
“Similar to what we observed with respect to opioid efficacy,” Dr Krupski said, “another one-third of our patients with mucositis required a change in opioid due to toxicity.”
Results—impact of race
Non-Caucasians patients (n=13) had a significantly higher incidence of mucositis (100%) than Caucasians (n=87, 72%, P=0.03).
Non-Caucasian patients also experienced significantly more pain with mucositis (P=0.03), even though the severity of mucositis did not differ between the 2 groups.
The total equivalent dose of morphine used also did not differ between the groups.
“This raises the question of whether there are factors other than race that may be contributing to this difference,” Dr Krupski said.
Genetic findings
The UGT2B7 gene encodes the main enzyme metabolizer of morphine, and SNPs of this gene (rs7668258 and rs7439366) vary by race.
Non-Caucasian patients had significantly more wild-type SNPs than Caucasian patients (P=0.001). And patients with the wild-type UGT2B7 genotype spent more total days on IV opioids than patients with variant alleles (P=0.03).
On examination of rs4633, a SNP of the COMT gene, which is a key regulator of pain perception, the investigators observed some different findings from what had previously been reported.
There was no difference in mucositis severity between patients with the wild-type and variant allele (P=0.3).
However, patients with the variant allele required more days to optimal pain control than patients with the wild-type allele (P=0.04). This finding confirmed increased pain sensitivity associated with the genotype, irrespective of race.
“[I]f this association holds true in future studies,” Dr Krupski explained, “one may be more aggressive in the initial opioid titration to optimize pain control.”
Despite limitations of sample size, especially with respect to non-Caucasian patients, the pilot study showed association, but not causation, with respect to genetic variants.
“Racial differences affect mucositis pain perception and opioid requirement,” Dr Krupski said. “If genotyping is not feasible, it is important to pay particular attention to this difference while managing patients’ pain from mucositis.”
“We have an opportunity here to improve our care. Therefore, our plan is to validate these findings in additional patients before we use them to achieve our ultimate goal: precision dosing of opioids to individual patients.” 
*Data in the abstract differ slightly from the presentation.
ORLANDO, FL—A pilot study to determine the burden of mucositis in pediatric patients undergoing hematopoietic stem cell transplant (HSCT) showed that more than 50% of patients required a change in their opioids either for toxicity or lack of efficacy.
Investigators also observed that patients’ genotypes were associated with time to optimal pain control, although this needs to be defined more clearly in larger prospective studies.
“Pain from mucositis is a major problem during the early post-transplant period in pediatric patients,” said M. Christa Krupski, DO, of Cincinnati Children’s Hospital Medical Center in Ohio.
The pain frequently requires intravenous (IV) pain medication, but adequate pain management is often delayed by the trial and error of finding the right agent or the right dose, Dr Krupski added.
She and her colleagues tried to find predictors of mucositis that would help optimize pain control and minimize adverse effects of pain medication.
Dr Krupski presented the group’s findings at the 2017 BMT Tandem Meetings as abstract 50*.
Based on the investigators’ previous experience using a pain chip, they hypothesized that host genetic polymorphisms would predict perception of mucositis pain, opioid efficacy, and opioid-induced adverse effects in pediatric patients undergoing HSCT.
The pain chip was comprised of a panel of 46 single-nucleotide polymorphisms (SNPs) in a set of candidate genes known to influence opioid effect.
Study design
In this single-institution, retrospective pilot study, investigators genotyped 100 consecutive HSCT patients using pre-transplant samples.
The team collected demographic and transplant data, information on the utilization of pain medication, and mucositis data according to the standard CTCAE guidelines.
“And it must be noted,” Dr Krupski said, “that many of our patients required total parenteral nutrition during the transplant process, which automatically made them a grade 3 for mucositis.”
The investigators assessed pain using 2 scales, the Face, Legs, Activity, Cry, Consolability (FLACC) Scale, which is an objective measurement, and the more subjective Numeric Rating Scores (NRS).
Demographics
Patients were a median age of 9.9 years (range, 0.5–32.8), 65% were male, 87% were Caucasian, and 13% non-Caucasian.
The main indications for transplant were malignancy (45%), immune deficiency/dysregulation (30%), and bone marrow failure syndrome (19%).
More than two-thirds (68%) of patients had received a myeloablative conditioning regimen.
Results—mucositis
Seventy-six patients experienced mucositis, three-quarters of whom (78%) had received a myeloablative conditioning regimen.
The majority of patients (57%) had severe mucositis, which developed a median of 3 days after transplant (range, -2 to 17).
Regarding treatment, 13 (17%) had medication as needed or no medication, 5 (7%) had scheduled IV opioid, and 58 (76%) had patient-controlled analgesia (PCA).
For analysis purposes, the investigators grouped together the scheduled IV opioid and PCA treatment groups.
Results—opioid efficacy
The opioid efficacy analysis was based on 63 patients.
Time to optimal pain control was a median of 7 days (range, 0–22), and the morphine dose at the time of optimal pain control was a median of 1.5 mg/kg (range, 0.2–15.7).
“You will note, though, the wide inter-patient variability,” Dr Krupski pointed out, “with some of our patients immediately achieving optimal pain control the day the medication was started and others taking over 3 weeks to reach optimal pain control.”
Investigators observed similar inter-patient variability in morphine equivalent use at the time of optimal pain control and total morphine equivalent use.
The total time patients were on PCA was a median of 16 days (range, 1–32), and the median total morphine equivalent use was 0.99 mg/kg/day (range, 0.10–8.07).
“Most interesting, though, was that 18 patients, or nearly one-third of the patients requiring IV opioids, required a change in this opioid due to poor efficacy,” Dr Krupski said.
Results—opioid toxicity
Thirty-two (51%) patients experienced at least 1 adverse effect from their pain medication.
Specific toxicities, based on 32 patients, included pruritus (53%), sedation (16%), and nausea/vomiting (9%). Six patients (19%) had more than one adverse event.
“Similar to what we observed with respect to opioid efficacy,” Dr Krupski said, “another one-third of our patients with mucositis required a change in opioid due to toxicity.”
Results—impact of race
Non-Caucasians patients (n=13) had a significantly higher incidence of mucositis (100%) than Caucasians (n=87, 72%, P=0.03).
Non-Caucasian patients also experienced significantly more pain with mucositis (P=0.03), even though the severity of mucositis did not differ between the 2 groups.
The total equivalent dose of morphine used also did not differ between the groups.
“This raises the question of whether there are factors other than race that may be contributing to this difference,” Dr Krupski said.
Genetic findings
The UGT2B7 gene encodes the main enzyme metabolizer of morphine, and SNPs of this gene (rs7668258 and rs7439366) vary by race.
Non-Caucasian patients had significantly more wild-type SNPs than Caucasian patients (P=0.001). And patients with the wild-type UGT2B7 genotype spent more total days on IV opioids than patients with variant alleles (P=0.03).
On examination of rs4633, a SNP of the COMT gene, which is a key regulator of pain perception, the investigators observed some different findings from what had previously been reported.
There was no difference in mucositis severity between patients with the wild-type and variant allele (P=0.3).
However, patients with the variant allele required more days to optimal pain control than patients with the wild-type allele (P=0.04). This finding confirmed increased pain sensitivity associated with the genotype, irrespective of race.
“[I]f this association holds true in future studies,” Dr Krupski explained, “one may be more aggressive in the initial opioid titration to optimize pain control.”
Despite limitations of sample size, especially with respect to non-Caucasian patients, the pilot study showed association, but not causation, with respect to genetic variants.
“Racial differences affect mucositis pain perception and opioid requirement,” Dr Krupski said. “If genotyping is not feasible, it is important to pay particular attention to this difference while managing patients’ pain from mucositis.”
“We have an opportunity here to improve our care. Therefore, our plan is to validate these findings in additional patients before we use them to achieve our ultimate goal: precision dosing of opioids to individual patients.”
*Data in the abstract differ slightly from the presentation.
ORLANDO, FL—A pilot study to determine the burden of mucositis in pediatric patients undergoing hematopoietic stem cell transplant (HSCT) showed that more than 50% of patients required a change in their opioids either for toxicity or lack of efficacy.
Investigators also observed that patients’ genotypes were associated with time to optimal pain control, although this needs to be defined more clearly in larger prospective studies.
“Pain from mucositis is a major problem during the early post-transplant period in pediatric patients,” said M. Christa Krupski, DO, of Cincinnati Children’s Hospital Medical Center in Ohio.
The pain frequently requires intravenous (IV) pain medication, but adequate pain management is often delayed by the trial and error of finding the right agent or the right dose, Dr Krupski added.
She and her colleagues tried to find predictors of mucositis that would help optimize pain control and minimize adverse effects of pain medication.
Dr Krupski presented the group’s findings at the 2017 BMT Tandem Meetings as abstract 50*.
Based on the investigators’ previous experience using a pain chip, they hypothesized that host genetic polymorphisms would predict perception of mucositis pain, opioid efficacy, and opioid-induced adverse effects in pediatric patients undergoing HSCT.
The pain chip was comprised of a panel of 46 single-nucleotide polymorphisms (SNPs) in a set of candidate genes known to influence opioid effect.
Study design
In this single-institution, retrospective pilot study, investigators genotyped 100 consecutive HSCT patients using pre-transplant samples.
The team collected demographic and transplant data, information on the utilization of pain medication, and mucositis data according to the standard CTCAE guidelines.
“And it must be noted,” Dr Krupski said, “that many of our patients required total parenteral nutrition during the transplant process, which automatically made them a grade 3 for mucositis.”
The investigators assessed pain using 2 scales, the Face, Legs, Activity, Cry, Consolability (FLACC) Scale, which is an objective measurement, and the more subjective Numeric Rating Scores (NRS).
Demographics
Patients were a median age of 9.9 years (range, 0.5–32.8), 65% were male, 87% were Caucasian, and 13% non-Caucasian.
The main indications for transplant were malignancy (45%), immune deficiency/dysregulation (30%), and bone marrow failure syndrome (19%).
More than two-thirds (68%) of patients had received a myeloablative conditioning regimen.
Results—mucositis
Seventy-six patients experienced mucositis, three-quarters of whom (78%) had received a myeloablative conditioning regimen.
The majority of patients (57%) had severe mucositis, which developed a median of 3 days after transplant (range, -2 to 17).
Regarding treatment, 13 (17%) had medication as needed or no medication, 5 (7%) had scheduled IV opioid, and 58 (76%) had patient-controlled analgesia (PCA).
For analysis purposes, the investigators grouped together the scheduled IV opioid and PCA treatment groups.
Results—opioid efficacy
The opioid efficacy analysis was based on 63 patients.
Time to optimal pain control was a median of 7 days (range, 0–22), and the morphine dose at the time of optimal pain control was a median of 1.5 mg/kg (range, 0.2–15.7).
“You will note, though, the wide inter-patient variability,” Dr Krupski pointed out, “with some of our patients immediately achieving optimal pain control the day the medication was started and others taking over 3 weeks to reach optimal pain control.”
Investigators observed similar inter-patient variability in morphine equivalent use at the time of optimal pain control and total morphine equivalent use.
The total time patients were on PCA was a median of 16 days (range, 1–32), and the median total morphine equivalent use was 0.99 mg/kg/day (range, 0.10–8.07).
“Most interesting, though, was that 18 patients, or nearly one-third of the patients requiring IV opioids, required a change in this opioid due to poor efficacy,” Dr Krupski said.
Results—opioid toxicity
Thirty-two (51%) patients experienced at least 1 adverse effect from their pain medication.
Specific toxicities, based on 32 patients, included pruritus (53%), sedation (16%), and nausea/vomiting (9%). Six patients (19%) had more than one adverse event.
“Similar to what we observed with respect to opioid efficacy,” Dr Krupski said, “another one-third of our patients with mucositis required a change in opioid due to toxicity.”
Results—impact of race
Non-Caucasians patients (n=13) had a significantly higher incidence of mucositis (100%) than Caucasians (n=87, 72%, P=0.03).
Non-Caucasian patients also experienced significantly more pain with mucositis (P=0.03), even though the severity of mucositis did not differ between the 2 groups.
The total equivalent dose of morphine used also did not differ between the groups.
“This raises the question of whether there are factors other than race that may be contributing to this difference,” Dr Krupski said.
Genetic findings
The UGT2B7 gene encodes the main enzyme metabolizer of morphine, and SNPs of this gene (rs7668258 and rs7439366) vary by race.
Non-Caucasian patients had significantly more wild-type SNPs than Caucasian patients (P=0.001). And patients with the wild-type UGT2B7 genotype spent more total days on IV opioids than patients with variant alleles (P=0.03).
On examination of rs4633, a SNP of the COMT gene, which is a key regulator of pain perception, the investigators observed some different findings from what had previously been reported.
There was no difference in mucositis severity between patients with the wild-type and variant allele (P=0.3).
However, patients with the variant allele required more days to optimal pain control than patients with the wild-type allele (P=0.04). This finding confirmed increased pain sensitivity associated with the genotype, irrespective of race.
“[I]f this association holds true in future studies,” Dr Krupski explained, “one may be more aggressive in the initial opioid titration to optimize pain control.”
Despite limitations of sample size, especially with respect to non-Caucasian patients, the pilot study showed association, but not causation, with respect to genetic variants.
“Racial differences affect mucositis pain perception and opioid requirement,” Dr Krupski said. “If genotyping is not feasible, it is important to pay particular attention to this difference while managing patients’ pain from mucositis.”
“We have an opportunity here to improve our care. Therefore, our plan is to validate these findings in additional patients before we use them to achieve our ultimate goal: precision dosing of opioids to individual patients.”
*Data in the abstract differ slightly from the presentation.