Predictors of Systemic Exposure to Oral 6MP During Maintenance in Adolescentsand Young Adults with Acute Lymphoblastic Leukemia

患有急性淋巴细胞白血病的青少年和年轻人在维持期间全身暴露于口服 6MP 的预测因子

• 批准号: 10576861
• 负责人: Julie Anna Wolfson
• 金额: $ 64.98万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-24 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10576861
• 关键词: 6-Mercaptopurine; Acute Lymphocytic Leukemia; Address; Adherence; Adolescent and Young Adult; Adult; Adult Acute Lymphocytic Leukemia; Age; Behavioral Sciences; Biometry; Caring; Child; Childhood; DNA; Diagnosis; Diagnostic; Disease Management; Disease remission; Disparity; Dose; Enrollment; Exposure to; Geography; Health Personnel; Health Services Research; Healthcare; Individual; Inferior; Infrastructure; Institution; Intervention; Interview; Investigation; Knowledge; Leukocytes; Maintenance; Maintenance Therapy; Malignant Neoplasms; Measures; Methods; Modeling; Monitor; Nucleotides; Oncology; Oral; Outcome; Outcomes and Health Services Research; Patient Care; Patient Self-Report; Patients; Pharmacogenetics; Pharmacology; Phase; Population; Process; Prospective cohort; Provider; Psychosocial Factor; Qualitative Research; Questionnaires; Recurrent disease; Regimen; Relapse; Research Design; Role; Services; Site; Social support; Structure; Survival Rate; System; Thioguanine; Time; chemotherapy; cohort; drug metabolism; health belief; health care delivery; improved; innovation; leukemia treatment; medication compliance; novel; oncology service; outcome disparities; peripheral blood; public health relevance; relapse risk; sociodemographics; young adult

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.

项目摘要/摘要