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Background: Adolescents and young adults (AYAs) receiving hematopoietic cell transplantation (HCT) are at high risk of poor psychosocial health. This study aimed to determine whether the Promoting Resilience in Stress Management (PRISM) intervention mitigated these risks during the first 6 months posttransplant. Methods: This multisite, parallel, randomized trial was conducted from April 2019 to March 2023. Eligible AYAs were aged 12–24 years, English speaking, and within 1 month of HCT for cancer or cancer predisposition syndrome. They were assigned 1:1 to PRISM (a brief, skills‐based intervention targeting "resilience resources" [stress management, goal setting, cognitive reframing, and meaning making]) or usual care (UC). Outcomes included total symptoms of depression and anxiety (Hospital Anxiety and Depression Scale; primary outcome), hope (Snyder Hope Scale), resilience (10‐item Connor–Davidson Resilience Scale), and health‐related quality of life (HRQOL; Pediatric Quality of Life Inventory Cancer Module). Analyses leveraged multivariable linear regressions; exploratory analyses assessed the influence of baseline depression or anxiety. Results: Of 94 enrolled and randomized AYAs, the mean age was 16.7 years (SD, 4.2); 43 (46%) were female, 56 (60%) were non‐Hispanic White, 22 (23%) were Hispanic, and nine (10%) were Black. Most (77%) had leukemia. Of n = 50 randomized to PRISM and n = 44 to UC, 37 (74%) and 33 (73%) completed all study procedures, respectively. In intention‐to‐treat analyses, PRISM did not affect 6‐month depression and anxiety (β = −1.1; 95% CI, −3.7 to 1.5), hope (β = 0.83; 95% CI, −3.3 to 4.9), resilience (β = −0.01; 95% CI, −3.0 to 3.0), or HRQOL (β = 1.5; 95% CI, −4.7 to 7.9). Among AYAs with preexisting anxiety or depression, PRISM recipients reported greater 6‐month improvements in hope (score change, +3.71; SD, 6.9) versus UC recipients (score change, −2.76; SD, 6.5) (p =.04). Conclusions: Resilience coaching did not influence outcomes in this sample. Exploratory findings suggest it may be more effective when directed toward those with concurrent distress. In a randomized trial conducted during the COVID‐19 pandemic among adolescents and young adults receiving hematopoietic cell transplantation for cancer or cancer predisposition, standardized resilience coaching did not influence patient‐reported depression. Exploratory findings suggest it may have promoted hopeful patterns of thoughts in the subset of participants who reported preexisting depression or anxiety. [ABSTRACT FROM AUTHOR]

1. Participants will be able to describe the potential impact of resilience-coaching programs for patients at risk for vs currently endorsing active psychological distress. 2. Participants will be able to describe the rationale for intention-to-treat analyses in randomized clinical trials, as well as opportunities to generate hypotheses from otherwise "negative" studies. In a randomized trial testing a brief, resilience-skills building intervention for adolescents and young adults with advanced blood cancers, the program seemed to work better among youth with mild-moderate distress. Promoting resilience may be more successful when people experience (and hope to improve) feelings of stress and distress. As we endeavor to deliver brief psychosocial interventions to improve quality of life among populations at risk, determining who may benefit from which interventions at which times is critical. In this randomized trial, we found that resilience-coaching may work better for youth already experiencing some degree of distress. Adolescents and Young Adults (AYAs) receiving Hematopoietic Cell Transplantation (HCT) are at high risk of depression. We aimed to determine if the Promoting Resilience in Stress Management (PRISM) intervention mitigated risks of depression during the first 3 months post-transplant. Secondary aims assessed PRISM's impact on anxiety, sense of resilience, hope, and health-related quality of life (HRQOL). We conducted this multi-site, parallel, non-blinded randomized trial from Oct/2019-Dec/2022. AYAs were eligible if they were 12-24 years-old, English- or Spanish-speaking, and within 1 month of HCT. They were assigned 1:1 to PRISM or Usual Care (UC). PRISM is a brief, skills-based, intervention taught by lay-coaches and targeting "resilience resources" (stress-management, goal-setting, cognitive-reframing, and meaning-making). Outcomes included AYA-reported depression (HADS-D) anxiety (HADS-A), resilience (CDRISC10), Hope (Hope scale), and HRQOL (PedsQL-cancer). We conducted intention-to-treat analyses using mixed linear regressions; exploratory analyses assessed the role of baseline depression (HADS-D>4). Ninety-four AYAs participated. Their mean age was 16.7 years (SD=4.2); they identified as female [n=43 (46%)], Non-Hispanic white [n=56 (60%)], Hispanic [n=22 (23%)], Non-Hispanic Black [n=9 (10%)]; Asian [n=5 (5%)], and "other"/mixed race [2 (2%)]. Of n=50 assigned to PRISM and n=44 to UC, n=22 (44%) and n=21 (48%) reported concurrent depression. Thirty-six (72%) PRISM-AYAs completed all 4 assigned sessions; n=10 (20%) completed 0-1. In intention-to-treat analyses, PRISM did not impact 3-month depression (b=0.04; 95% CI-1.5,1.6), anxiety (b=0.3; -1.1,1.7), resilience (b=1.1; -1.8,3.9), hope (b=2.6; -1.1,6.2), or HRQOL (b=5.2; -0.2,11.0). Stratified analyses suggested PRISM may help AYAs with active depression (Resilience b=3.6; 2.0,9.3; Hope b=5.7; 0.5,11.0; HRQOL b=7.2; -2.2,17.0). We observed no measurable impact of resilience-coaching among a cohort of AYAs receiving HCT; secondary analyses suggest the program may be more effective when limited to those with concurrent distress. Successfully promoting resilience may require recognizing and targeting those who most need it most. Psychosocial support/Pediatrics [ABSTRACT FROM AUTHOR]