PROJECT SUMMARY / ABSTRACT
Patients diagnosed with cancer between the ages of 15-39y have not seen the same improvement in survival
when compared with patients diagnosed as children (<15y). These patients have received special designation
by the NCI as adolescents and young adults (AYA), accompanied by a mandate to address these outcome
disparities. Acute lymphoblastic leukemia (ALL) epitomizes this phenomenon, where survival rates in AYA
continue to lag behind children (5y overall survival: 1-14y: 86%; 15-21: 56%; 22-29: 42%; 30-39: 35%). Across
pediatric-inspired and adult-style therapy regimens, ALL therapy includes a prolonged (~2y) maintenance phase
of chemotherapy requiring daily oral 6-mercaptopurine (6MP). A large investigation recently confirmed that
inadequate systemic exposure to 6MP is associated with an increased risk of relapse; to measure systemic 6MP
exposure, this comprehensive approach assessed the levels of a 6MP metabolite (thioguanine nucleotide [TG])
incorporated into DNA (DNA-TG). Several AYA-specific factors likely contribute to systemic 6MP exposure and
have not been examined systematically. These factors are likely related to both the AYA patient (6MP adherence)
and healthcare (disease management, reflected by the provider-prescribed 6MP dose intensity [DI]), as well as
the barriers and facilitators within these domains. We hypothesize that systemic exposure to 6MP will correlate
with both 6MP adherence (in the patient domain) and disease management, as represented by provider-
prescribed 6MP DI (in the healthcare domain). We will examine these associations between DNA-TG levels and
both 6MP adherence and 6MP DI, adjusting for pharmacogenetics. We will then identify barriers/ facilitators to
both 6MP adherence and disease management, using a mixed methods convergent parallel study design, both
quantitatively determining the predictors of adherence and 6MP DI, and qualitatively describing the perspectives
of both the patients and healthcare providers. We will conduct this study using a prospective cohort of AYA
patients in ALL maintenance therapy across a national 14-site consortium of multiple types of facilities and
oncology practices. For 6 months per patient, 6MP adherence will be monitored electronically and monthly DNA-
TG levels will be followed (peripheral blood). Patient questionnaires will capture self-reported barriers and
facilitators of adherence as well as sociodemographics; institution-level questionnaires will capture healthcare
factors. Findings from this study have the potential to identify both patient-related and healthcare-related targets
amenable to interventions with the potential to mitigate AYA outcome disparities in AYA patients with ALL.
Furthermore, this study establishes the infrastructure to continue to follow this cohort for relapse, and conduct
intervention(s) informed by this proposed trial within a novel AYA-focused consortium.
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