A digital health approach to improving PTSD symptom management among cancer transplant survivors using a SMART design.

550 Background: Hematopoietic cell transplantation (HCT) cancer survivors face elevated risk for posttraumatic stress disorder (PTSD) symptoms, yet access to effective treatment remains limited. This NCI-funded study (R01-CA244172) evaluated a stepped-care, adaptive digital health intervention using a Sequential Multiple Assignment Randomized Trial (SMART) design to optimize PTSD symptom management. Methods: Adult cancer survivors who received autologous or allogeneic HCT 1–5 years prior, were in remission, and identified through transplant registries were recruited from three cancer centers and BMT Infonet. Inclusion criteria required significant PTSD symptoms [PTSD Checklist (PCL-5) score ≥31] and access to a smart device. Participants were randomized to the Cancer Distress Coach (CaDC) app (n=237) or Usual Care (n=240). At Month 1, non-responders (i.e., <5-point PCL-5 reduction) were re-randomized to receive CaDC+Coaching (i.e., app+therapist/coach; n=80) or HCT-specific CBT for PTSD (CBT-PTSD; n=80) virtually. PTSD symptoms (PCL-5) were assessed at Month 3 (post-intervention) and Month 6 (follow-up). The design enabled evaluation of initial treatment efficacy and six stepped-care strategies. Results: Participants (N=477) were majority female (63%), white (82%), with a mean age of 52.6±13.7. Those in the CaDC arm showed greater PTSD symptom reduction at Month 3 compared to Usual Care (p=0.0378). Regimes including CBT-PTSD showed improvements over those without at 3 and 6 months. At 6 months, regimes beginning with CaDC were associated with greater PCL-5 score reductions than regimes beginning with Usual Care. All regimes with CaDC+Coaching and CBT-PTSD had large Cohen's d effect sizes at Month 3 (0.769, 0.887) and Month 6 (0.846, 0.920). Conclusions: This SMART study demonstrated the effectiveness of a stepped-care, digital health approach for PTSD symptom management in HCT cancer survivors. CaDC is a promising first-line intervention, while CaDC+Coaching and CBT-PTSD offer substantial added benefits for non-responders. These findings inform scalable, personalized distress management strategies for cancer survivors. Clinical trial information: NCT04058795 .