Although it is the most convenient method for monitoring oral 6-mercaptopurine (6MP) intake in pediatric patients with acute lymphocytic leukemia (ALL), self-reporting frequently becomes over-reporting, according to a report from the Children’s Oncology Group presented at the 2015 ASH Annual Meeting. Inaccurate records of chemotherapy intake could lead to higher risks of relapse according to investigators, led by Wendy Landier, PhD, CRNP, from the Institute for Cancer Outcomes and Survivorship at the University of Alabama at Birmingham, noted.
“We have previously shown that poor systemic exposure to 6MP (as measured by poor adherence to oral 6MP) is associated with increased risk of relapse,” Dr. Landier said during her presentation of the results. “Accurate assessment of 6MP intake is, therefore, critical to ensure timely interventions.”
To determine the accuracy of subjective reporting among pediatric patients with ALL, and the possible predictors of over-reporting, investigators compared self-reported oral 6MP intake (subjective record group) with electronically monitored intake (objective record group) in 416 young patients with ALL.
In the subjective record group, the patient (or the patient’s parent, if the patient was younger than 12 years old) self-reported the number of days that the 6MP had been taken over the past month at the end of each of the four study months. In the objective record group, 6MP was measured electronically using the Medication Event Management System (MEMS) tracking cap, which recorded the dates and times whenever the 6MP bottle was opened, continuing for four study months per patient.
All patients included in the study (median age = 6 years; age range = 2-20 years) were in first remission and receiving 75 mg/m2 once-daily 6MP as maintenance therapy. Thirty-nine percent of patients had high-risk disease and 36 percent were Caucasian.
At the end of the study period, the data from the MEMS cap were compared with the self-report records. Patients were then categorized as either:
- perfect reporters: objective and subjective records matched
- over-reporters: 6MP intakes was greater on self-report than MEMS for 5 or more days for more than half of the study months
- others: 6MP intake was different on self-report than MEMS for less than 5 days or less than half of the study months
Only 50 patients (12%) were identified as “perfect reporters,” Dr. Landier and colleagues wrote, while 98 (23.6%) were identified as “over-reporters.” The remaining 64.4 percent were classified as “others.”
A total of 1,344 patient-months of self-report and MEMS data were evaluated. As seen in TABLE 1, mean days of reported 6MP intake per month were higher in the subjective record group (ranging from 25.8-26.1 days) than in the objective record group (22.8-25.4 days).
Eighty-eight percent of patients/parents over-reported the number of days 6MP was taken, with most over-reporting by one to four days. The difference between objective and subjective records due to over-reporting was:
- <0 days in 2 patients (<1%)
- 0 days in 50 patients (12%)
- 1-4 days in 266 patients (64%)
- ≥5 days in 98 patients (24%)
The authors identified the following as independent predictors of over-reporting: older age, non-white race, a household in which fathers did not attend college, and 6MP non-adherence (TABLE 2).
Overall, 40.4 percent of all patients were non-adherent to oral 6MP. Notably, non-adherent patients were 8.6 times more likely than adherent patients to over-report 6MP intake. “While 77 of 98 (78.6%) of over-reporters were non-adherent, only one of the 50 (2%) of the perfect reporters was non-adherent,” Dr. Landier and colleagues concluded. “Subjective reporting of 6MP ingestion during maintenance therapy for childhood ALL may be unreliable, particularly in non-adherent patients, and should be used with caution.”
Landier W, Chen Y, Hageman L, et al. 6-Mercaptopurine (6MP) intake during maintenance for childhood acute lymphoblastic leukemia (ALL) – a comparison of self-report and electronic monitoring: a report from the Children’s Oncology Group (COG) study AALL03N1. Abstract #82. Presented at the 2015 ASH Annual Meeting, December 5, 2015; Orlando, Florida.
|TABLE 1. 6MP Intake by Self-Report Versus MEMS|
|Study Month||Patients (N)||Self-report, days
|MEMS, days (mean, SD)||
|1||275||26.1 (4.5)||25.4 (4.5)||0.58||<0.0433|
|2||370||26.1 (4.3)||22.8 (6.4)||0.44||<0.0001|
|3||355||25.9 (4.9)||23.7 (6.3)||0.36||<0.0001|
|4||344||25.8 (5.3)||23.2 (6.7)||0.43||<0.0001|
|TABLE 2. Predictors of Over-Reporting of 6MP Intake|
|Odds Ratio||95% CI||p Value|
|Age ≥12 (per year)||1.07||1.0-1.1||0.04|
|Paternal education lower than college-level||2.1||1.1-4.1||0.02|
|6MP non-adherence <95%||8.6||4.7-15.9||<0.001|