Roxanne Nelson, BSN, RN

December 05, 2015

ORLANDO, Florida — Durable remissions in childhood acute lymphocytic leukemia (ALL) require about 2 years of maintenance chemotherapy that includes daily doses of oral 6-mercaptopurine (6MP), and if children don't take this drug, they could be at risk of relapse. A new study shows that children and their parents often report that the drug has been taken when in fact it hasn't.

Approximately 25% of children or their caregivers overreported 6MP intake, while only 12% were identified as "perfect reporters," where the report correlated with electronic monitoring of when the drug was taken. The remaining 64.4% of children and caregivers fell in between the two ends of the spectrum.

The authors also found that overreporting was more likely to occur in patients who were nonadherent to 6MP, those who were 12 years of age or older, were from a minority race, or were from households with lower parental education.

"Subjective overreporting of 6MP intake during maintenance therapy for childhood ALL is common, particularly in nonadherent patients, and should be used with caution," explained lead author Wendy Landier, PhD, CRNP, from the University of Alabama, Birmingham.

Dr Wendy Landier

Speaking at a press briefing here at the American Society of Hematology (ASH) 57th Annual Meeting, she emphasized that the maintenance chemotherapy regimen was important to prevent relapses. In the COG AALL03N1 study, electronically measured 6MP adherence rates <95% were associated with a 3.7-fold increased risk of relapse, she noted.

An accurate assessment of 6MP intake is crucial to ensure timely intervention for nonadherent patients, and self-report is a convenient and inexpensive method of monitoring the use of 6MP in the clinical setting, she explained. However, literature in the nononcology setting has indicated that self-reporting is subject to overreporting, and the extent of overreporting is directly related to the number of missed doses.

As the accuracy of self-/parental reporting of 6MP intake during ALL maintenance is not known, Dr Landier and colleagues addressed the issue by comparing self-reported 6MP intake with electronic monitoring, with the goal of identifying predictors of overreporting.

She emphasized, however, that this study was focused on the issue of overreporting and not nonadherence. "We were digging deeper into the data to compare the correlation between subjective and objective reporting," Dr Landier pointed out. "These people knew they were in a clinical trial and they knew that they were being monitored and they still overreported."

Majority Overreported Intake

The cohort included 416 children with ALL in first remission who were receiving oral 6MP (75 mg/m2/day) during their maintenance regimen. The median age at study entry was 6 years old (range, 2 to 20 years), and 36% were non-Hispanic white, 67% were male, 38.4% had high-risk disease, and 40.4% were nonadherent to oral 6MP therapy.

The intake of 6MP was measured electronically using the Medication Event Management System (MEMS; objective record), which recorded the dates/times of each 6MP bottle opening over 4 study months per patient (28 days/month). The bottle containing 6MP had a TrackCap microprocessor chip that recorded the date and time of each bottle opening. These data were downloaded at end of study period and then compared with self-report.

For the subjective data, the patient or parent (if patient was younger than 12 years old) self-reported the number of days that 6MP had been taken during the past month, at the end of each of the 4 study months.

A total of 1344 patient-months of self-report and MEMS data were evaluated. The objective and subjective records of 6MP intake were then compared for each patient by study month, and patients were categorized as "perfect reporters" (self-report = MEMS report), "overreporters" (self-report > MEMS report ≥ 5 days/month for > 50% of study months) and "others."

When comparing subjective to objective 6MP intake, the mean (±SD) days of 6MP ingestion per month ranged from 25.8±5.3 to 26.1±4.5 by subjective reporting vs 22.8±6.4 to 25.4±4.5 by objective measurement (adjusted mean values by generalized estimating equations analysis).

Dr Landier and her colleagues found that when looking at the difference in days between self-report vs electronic monitoring, only 50 patients (12%) missed 0 days. Double that number (98 patients, 24%) missed 5 or more days, and 266 (64.4%) missed between 1 and 4 days.

Overall, 88% of patients/parents overreported a number of days that been 6MP taken, she explained.

When evaluating predictors of overreporting, they found nonwhite race (Hispanic, odds radio [OR] 2.4, = .02; Asian, OR 3.1, = .02; black, OR 5.3, P < .001), level of paternal education (<college, OR 2.1, = .02), and 6MP nonadherence (OR 8.6, P < .0001) were all predictive of overreporting.

While 77/98 (78.6%) of overreporters were nonadherent, only one of the 50 (2%) of the perfect reporters was nonadherent.

Drugs Don't Work Unless You Take Them

There are many pharmaceutical therapies available now, commented Mark Crowther, MD, professor and chair in the department of pathology and molecular medicine of McMaster University in Hamilton, Ontario, Canada.

"Some of them are complex, some of them are expensive, some of them are revolutionary, but if the patients don't take them they can't possibly work," said Dr Crowther, who moderated the briefing. "This whole issue of how you maximally use the therapies is a huge problem for medicine.

"While it's great to have advances, we have to make sure that we are using the therapies that we have now appropriately," he noted. "And that is probably the most important message. When a patient fails, did they fail because the medication didn't work or because they weren't taking it?"

Dr Landier reported no relevant financial relationships. Coauthors William E Evans, PharmD, and Mary V Relling, PharmD, report receiving royalties from licensing TPMT genotyping from Prometheus Labs.

American Society of Hematology (ASH) 57th Annual Meeting; Orlando, Florida. Abstract 82, presented December 5, 2015.

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