Targeting Stress Biology after HCT: Mindfulness for Insomnia Improves Sleep and Reduces Proinflammatory Gene Expression

Sleep disruption is common among hematopoietic stem cell transplantation (HCT) patients and associated with increased inflammation and reduced immune response. Increased expression of proinflammatory genes is predictive of adverse HCT outcomes, including increased relapse. Mindfulness-based interventions (MBIs) can improve sleep quality and enhance immune function, yet their effect on these factors in the immediate peri-HCT setting is unknown. To investigate the effect of an insomnia-based MBI on sleep and transcriptomic markers of inflammation among multiple myeloma patients receiving their first autologous HCT. In this randomized controlled pilot study, patients (N=7) with multiple myeloma undergoing autologous HCT received pre-transplant instruction in Mindfulness Awareness Practices for Insomnia (MAP-I; N=3) or Sleep Hygiene Education (SHE; N=4). Biospecimens and sleep surveys were collected at five peri-transplant timepoints (T1: Day -42, T2: Day -2; T3: Day +14, T4: Day +60, T5: Day +100). Sleep was measured via the Pittsburgh Sleep Quality Index (PSQI); a >3 point change from baseline indicated clinical significance. Proinflammatory gene expression was measured by RNA sequencing of whole blood samples. Analyses focused on a composite of 19 pre-specified inflammatory genes. MAP-I was associated with a significant decrease in proinflammatory gene expression at T4 and T5 in an intervention vs. time interaction (F[4, 399]=2.53, p=.04; 41% relative reduction from baseline at both time points, both p < .01). Analysis controlled for person-level (age, race, BMI, smoking) and leukocyte subtype variables. MAP-I but not SHE was associated with a clinically significant improvement in PSQI scores from baseline to T4 and T5 (MAP-I: -4, -4; SHE-2.5, -3; respectively). MAP-I produced clinically meaningful improvement in sleep and sustained reduction in proinflammatory gene expression at 60–100 days post-HCT. Although the intervention was delivered weeks earlier, these effects emerged during immune reconstitution, suggesting a conditioning-like influence priming recovery toward a less inflammatory setpoint. These results indicate that a peri-HCT, sleep-focused MBI may be a useful adjunct to standard care. Larger, mechanistic trials are needed to replicate and clarify the pathway.