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. 2017 Sep 6;12(9):e0183119.
doi: 10.1371/journal.pone.0183119. eCollection 2017.

Adherence to 6-Mercaptopurine in children and adolescents with Acute Lymphoblastic Leukemia

Mervat Alsous  1 , Rana Abu Farha  1 , Eman Alefishat  2 , Suha Al Omar  3 , Deema Momani  3 , Alia Gharabli  3 , James McElnay  4 , Robert Horne  5 , Rawad Rihani  6
Affiliations

Adherence to 6-Mercaptopurine in children and adolescents with Acute Lymphoblastic Leukemia

Mervat Alsous et al. PLoS One. .

Abstract

Objective: Studies on children with Acute Lymphoblastic Leukemia (ALL) reported non-adherence in 2-54% of cases. The primary objective of this study was to assess rates of adherence to 6-MP using two different methods in children and adolescents with ALL. Secondary aim was to identify factors that influence adherence to 6-MP in children with ALL.

Methods: All eligible children with ALL who are (≤ 19) years old and receive 6-MP therapy for at least 1 month were approached to participate in the study. A total of 52 children with ALL and their primary caregivers were recruited. Adherence measures included an objective method (measuring 6-MP metabolites in packed Red Blood Cells (RBCs)) and a subjective method (using parent and child self-report via the Medication Adherence Report Scale; MARS; Adherence was defined as 90% or greater).

Results: Rates of adherence varied across the measurement methods. Packed RBCs sample analysis indicated forty-four patients (84.6%) to be adherent. Using the MARS questionnaires, a total of 49 children (94.2%) were classified as being adherent according to the parental MARS questionnaire scores, while all the 15 children (100%) who answered the MARS (child) questionnaire were classified as adherent. Overall adherence rate was 80.8% within the studied population.

Conclusion: MARS scale was shown to overestimate adherence compared to measurement of 6-MP metabolites in the blood. A combination of both methods led to increased detection of non-adherence to thiopurine in children with ALL.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Scatter plot showing the four different clusters formed after hierarchical clustering of the ALL study sample using 20th percentile of metabolite levels as cutoff point.
Data for 6-mMPNs and 6-TGNs are the metabolite levels (adjusted per dose/SA). Cluster A (i.e. above 20% cutoff point) was characterized by high levels of 6-TGN levels and 6-mMP levels (adherent patients). Cluster B was characterized by high levels of 6-mMP but with low 6-TGN concentrations, it is expected that those patients in Cluster B had higher TPMT activity than those in cluster A, which would explain the shift in 6-MP metabolism toward 6-mMP production in those patients. Cluster C was characterized by low levels of both 6-mMP levels and 6-TGN (non-adherent patients). Cluster D patients have low levels of 6-mMP levels and high levels of 6-TGN (Lower TPMT activity in patients in Cluster D compared to those in cluster A would explain the shift in 6-MP metabolism toward 6-TG production in those patients).
See this image and copyright information in PMC

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