Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a potentially curative procedure for many hematologic malignancies. Due to the intensive conditioning regimen (e.g., radiotherapy, chemotherapy) and post-transplant complications, allo-SCT is associated with multiple physical and psychological side effects including symptom burden (e.g., fatigue, pain), and poor psychosocial function and emotional distress (e.g., anxiety, depression) that impair health-related quality of life (HRQoL), and occur within the context of following a strict self-management protocol to prevent treatment-related complications. Novel, integrative, engaging, low-demand and scalable programs to reduce symptom burden and improve health related quality of life (HRQoL) and health outcomes in allo-SCT are needed, yet limited work has addressed the development and implementation music therapy—a therapeutic approach that can favorably impact health outcomes in cancer survivors. Mindfulness-based music therapy (MBMT) blends core elements of mindfulness and tailored music intervention components (e.g., songwriting, instrument playing) delivered by a trained music therapist. Our transdisciplinary team has shown that (a) MBMT reduces negative mood, fatigue, and anxiety in breast cancer survivors, (b) stress management and mindfulness improve physiological adjustment (e.g., reduced inflammation) and HRQoL in various cancer survivorship populations, and (c) that eHealth platforms can facilitate effective delivery of psychosocial interventions in cancer patients and survivors. However, studies implementing the first step in developing and evaluating well-designed, feasible, acceptable, and reproducible eHealth facilitated MBMT (eMBMT) interventions to improve patient outcomes are limited. Further, how specific music therapy components impact psychosocial (e.g., anxiety, depression) and physiological (e.g., inflammation, immunocompetence) mechanisms is not well understood. Using our expertise in mix-methods approaches, eHealth, allo-SCT, and MBMT, we address these gaps and propose to establish acceptability, feasibility and intended effects of a novel eHealth facilitated eMBMT in reducing symptom burden and improving HRQoL (Primary Outcomes), improving psychosocial and physiological adaptation and (e.g., cancer distress, reduced inflammation, T-cell recovery/immune reconstitution) (eMBMT Mechanisms), and ameliorating disease activity (e.g., GVHD) (Secondary Outcomes) in patients undergoing allo-SCT. In the R61 Phase we implement a mixed-methods (e.g., focus groups, small RCT) design to finalize eMBMT and a mindfulness meditation (eMM) control condition, establish feasibility and begin to identify music therapy components that favorably impact our study outcomes/mechanisms. In our R33 Phase we conduct a larger scale pilot RCT informed by the R61 findings to establish intended effects of eMBMT music therapy components on HRQOL, symptom burden and psychosocial and physiologic adaptation. Findings will guide a large-scale RCT with long-term follow-up and additional clinical outcomes.