This article is more than 5 years old. Information may no longer be current.
Therapy restrictions may hinder adherence in children with ALL
Click Here to Manage Email Alerts
Commonly practiced restrictions to take oral mercaptopurine in the evening without food or dairy products may negatively affect treatment adherence among children with acute lymphocytic leukemia, according to results of a prospective study.
Further, these restrictions did not appear to affect outcomes.
Therapy for childhood ALL involves a 2-year maintenance period with daily oral mercaptopurine (6-MP), recommendations for which state it should be taken every evening on an empty stomach without food or dairy products. Although research has shown that poor adherence to 6-MP is prevalent and associated with increased risk for relapse, the consensus recommendations on 6-MP ingestion restrictions are based on limited and conflicting evidence.
“On the basis of these findings, we believe that future recommendations regarding 6-MP intake during maintenance therapy for childhood ALL should aim to simplify and reduce variability in administration and enhance adherence — by removing restrictions regarding coadministration of food and milk products and emphasizing the importance of establishing a consistent daily 6-MP routine that integrates well into the family lifestyle — to maximize the likelihood of success,” Wendy Landier, PhD, RN, CRNP, associate professor in the division of pediatric hematology-oncology at University of Alabama at Birmingham School of Medicine, and colleagues wrote.
Researchers evaluated the association between 6-MP ingestion practices and adherence, red cell thioguanine nucleotide levels — to represent systemic exposure to 6-MP — and risk for relapse.
The analysis included 441 children (median age, 6 years; range, 2-20) with ALL from 87 institutions who were receiving 75 mg/m2 oral 6-MP daily.
Researchers used the Medication Event Monitoring System (WestRock Healthcare in Switzerland) — a microelectronic technology to track every date and time the bottle was opened — to track patient adherence over 48,086 patient-days. Researchers categorized patients as receiving their medication in the morning/midday or evening/night local time if more than 75% of doses fell within one of the time frames; otherwise, patients took 6-MP at various times of day.
Patients or their parents also completed self-report questionnaires that detailed ingestion habits as took 6-MP with food vs. without food, took 6-MP with milk/dairy vs. without milk/dairy, swallowed 6-MP tablet whole vs. tablet crushed or chewed, and followed an established 6-MP routine vs. no routine. The researchers assessed self-reported data on days 29, 57, 113 and 141.
Overall, the researchers observed variability in 6-MP ingestion habits. Nine percent of patients took their 6-MP dose at times other than the evening, 14% had no set routine for taking it, 15% reported taking it with milk or dairy products, 28% reported taking it with food, 33% crushed or chewed the tablet before swallowing, and 43.8% were nonadherent.
Among patients who adhered to medication, the researchers found no association between red cell thioguanine nucleotide levels (measured in pmol/8 x 108) and taking 6-MP with or without food (206.1 ± 107.1 vs. 220.6 ± 121.6); with or without dairy (220.1 ± 87.8 vs. 216.3 ± 121.3); or in the evening/night (218.8 ± 119.7) compared with in the morning/midday (195.5 ± 82.3) or various times of day (174.8 ± 93.4).
However, the researchers found a relationship between 6-MP ingestion practices and adherence.
Taking 6-MP with dairy (OR = 1.9; 95% CI, 1.3-2.9) and at various times (OR = 3.4; 95% CI, 1.8-6.3) increased likelihood of nonadherence.
After adjusting for adherence and other prognostic factors, researchers observed no association between relapse risk and taking 6-MP with food (HR = 0.7; 95% CI, 0.3-1.9), with dairy (HR = 0.3; 95% CI, 0.07-1.5), in the morning/midday vs. evening/night (HR = 1.1; 95% CI, 0.2-7.8), at various times vs. evening/night (HR = 0.3; 95% CI, 0.04-2.7) and swallowing the tablet whole vs. taking it crushed/chewed (HR = 0.8; 95% CI, 0.3-2.1).
“Because it is clear that 6-MP will not be absorbed at all if it is not taken, our findings point to the importance of prioritizing adherence over restrictions regarding 6-MP ingestion,” the researchers wrote. – by Melinda Stevens
Disclosures: Landier reports institutional research funding from Merck Sharp & Dohme. Please see the full study for a list of all other researchers’ relevant financial disclosures.
Click Here to Manage Email Alerts