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The Promoting Resilience in Stress Management (PRISM) intervention is a resilience-coaching program that has been shown to mitigate distress and improve quality of life among AYAs receiving chemotherapy for newly diagnosed or advanced cancer. This article describes the protocol of an ongoing randomized-controlled trial (RCT) examining the efficacy of PRISM among AYAs receiving HCT for cancer and\/or blood disorders.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods\/design<\/jats:title><jats:p>The goal of this multi-site, parallel, RCT is to evaluate the effect of PRISM compared to psychosocial usual care (UC) among AYAs receiving HCT. Our primary hypothesis is that AYAs who receive PRISM will report lower depression and anxiety 6-months following enrollment compared to those who receive UC. The PRISM program includes four scripted coaching sessions targeting skills in stress-management, goal setting, cognitive-restructuring, and meaning-making, followed by a facilitated family meeting. Sessions are delivered one on one, 1\u20132\u2009weeks apart, in-person or via videoconference. We aim to recruit 90 AYAs from 4 US pediatric AYA oncology centers. Eligible AYAs are aged 12\u201324\u2009years; receiving HCT for malignancy or a bone marrow failure syndrome associated with cancer predisposition; &lt;\u20094\u2009weeks from their HCT date; able to speak English and read in English or Spanish; and cognitively able to complete sessions. Enrolled AYAs are randomized 1:1 within each site to receive PRISM+UC or UC alone. AYAs on both study-arms complete patient-reported outcome surveys at baseline, 3- and 6-months. Age-valid instruments assess depression and anxiety, overall and cancer-specific health-related quality of life, symptom burden, resilience, and hope. Covariate-adjusted regression models will compare AYA-reported depression and anxiety at 6-months in the PRISM versus UC groups. Secondary and exploratory objectives include assessments of PRISM\u2019s cost-effectiveness and its impact on (i) parent and caregiver quality of life and mental health, (ii) pharmaco-adherence to oral graft-versus-host disease (GVHD) prophylaxis, (iii) biologic outcomes such as transplant engraftment and graft-versus-host disease, and (iv) biomarkers of stress such as heart rate variability and the Conserved Transcriptional Response to Adversity (CTRA) gene expression profile.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>If successful, this study has the potential to address a critical gap in whole-patient care for AYAs receiving HCT.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial registration<\/jats:title><jats:p>ClinicalTrials.gov Identifier<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03640325?term=NCT03640325&amp;draw=2&amp;rank=1\">NCT03640325<\/jats:ext-link>, August 21, 2018.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12904-022-00966-9","type":"journal-article","created":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T01:02:25Z","timestamp":1652922145000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The Promoting Resilience in Stress Management (PRISM) intervention for adolescents and young adults receiving hematopoietic cell transplantation: a randomized controlled trial protocol"],"prefix":"10.1186","volume":"21","author":[{"given":"Kaitlyn M.","family":"Fladeboe","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha","family":"Scott","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liam","family":"Comiskey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joyce P.","family":"Yi-Frazier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7608-607X","authenticated-orcid":false,"given":"Abby R.","family":"Rosenberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,5,19]]},"reference":[{"issue":"5","key":"966_CR1","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1182\/blood-2011-01-331835","volume":"118","author":"SH Armenian","year":"2011","unstructured":"Armenian SH, Sun CL, Kawashima T, et al. 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