Unfavorable transcriptome profiles and social disadvantage in hematopoietic cell transplantation: a CIBMTR analysis.

Patient-reported outcomes (PROs) capture subjective social determinants of health (SDOH), which can affect health outcomes through the stress response pathway. The Conserved Transcriptional Response to Adversity (CTRA) is a stress-mediated pro-inflammatory transcriptomic pattern that has been linked to adverse hematopoietic cell transplant (HCT) outcomes. This study examined the association of pre-transplant CTRA with patient-reported SDOH in allogeneic HCT recipients. In this cross-sectional study, pre-HCT SDOH-related PROs included the 36-Item Short Form Health Survey (SF-36) and the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT). CTRA was assessed by RNA sequencing of whole blood specimens, with mixed effects linear regression models relating CTRA expression to PRO scores while controlling for age, sex, race, disease, and performance status. Among n=121 patients, median age was 54 years, 42% were female, and 91% White. CTRA was elevated in participants reporting lower scores on the FACT-BMT (p=0.003), including the General (p=0.003) and BMT-specific (p=0.014) components. Effects were driven by the Social Well-Being domain (p=0.0001). This corresponded to an 8-15% difference in CTRA RNA expression across a 4-SD range in patient-reported SDOH. Ancillary bioinformatics analyses confirmed the association of well-being with reduced pro-inflammatory transcription pathway activity (CREB, NF-kB, and AP-1). In conclusion, HCT patients who experience unfavorable social conditions show elevated CTRA expression in pre-transplant blood samples. These data highlight the biologic sequelae of social well-being and community context and suggest a potential molecular mechanism for the impact of social gradients in HCT outcomes. Targeting this pathway could optimize outcomes in this high-risk population.