CMV exposure drives long-term CD57+ CD4 memory T-cell inflation following allogeneic stem cell transplant.

Donor and recipient cytomegalovirus (CMV) serostatus correlate with transplant-related mortality that is associated with reduced survival following allogeneic stem cell transplant (SCT). Prior epidemiologic studies have suggested that CMV seronegative recipients (R-) receiving a CMV-seropositive graft (D+) experience inferior outcomes compared with other serostatus combinations, an observation that appears independent of viral reactivation. We therefore investigated the hypothesis that prior donor CMV exposure irreversibly modifies immunologic function after SCT. We identified a CD4+/CD57+/CD27- T-cell subset that was differentially expressed between D+ and D- transplants and validated results with 120 patient samples. This T-cell subset represents an average of 2.9% (D-/R-), 18% (D-/R+), 12% (D+/R-), and 19.6% (D+/R+) (P < .0001) of the total CD4+ T-cell compartment and stably persists for at least several years post-SCT. Even in the absence of CMV reactivation post-SCT, D+/R- transplants displayed a significant enrichment of these cells compared with D-/R- transplants (P = .0078). These are effector memory cells (CCR7-/CD45RA+/-) that express T-bet, Eomesodermin, granzyme B, secrete Th1 cytokines, and are enriched in CMV-specific T cells. These cells are associated with decreased T-cell receptor diversity (P < .0001) and reduced proportions of major histocompatibility class (MHC) II expressing classical monocytes (P < .0001), myeloid (P = .024), and plasmacytoid dendritic cells (P = .0014). These data describe a highly expanded CD4+ T-cell population and putative mechanisms by which prior donor or recipient CMV exposure may create a lasting immunologic imprint following SCT, providing a rationale for using D- grafts for R- transplant recipients.

Improving Quality of Life in Hematopoietic Stem Cell Transplantation Survivors Through a Positive Psychology Intervention.

Despite advances in transplantation medicine, psychological distress and quality of life and functional deficits continue to compromise survivorship after hematopoietic stem cell transplantation (HSCT). With increasing numbers of HSCT survivors, supportive oncology interventions that target health-related outcomes in HSCT survivorship are needed. Here we aimed to test the feasibility and acceptability of a group format phone-delivered positive psychology (PP) intervention in HSCT survivors. This is a one-arm pilot study design that adapted and tested an individual PP intervention used in cardiac disease to a phone-delivered group-based program for HSCT survivors who were .4 to 39 years post-transplantation. All participants received an 8-session weekly PP intervention. We assessed feasibility by the enrollment and intervention completion rates. We examined acceptability on a 10-point Likert scale of ease and utility. Unstructured qualitative interviews were used to obtain participant feedback on the intervention for future application in a larger trial. Self-reported assessments on psychological, functional, and quality of life outcomes were administered at baseline and at follow-up (the end of the intervention). Of 64 eligible participants, 29 (45%) enrolled in the study. For the main aim of intervention feasibility and acceptability, participants completed 96% of all PP sessions and rated the ease (7.6 ± 1.7) and utility (8.1 ± 1.1) of sessions highly. Of the self-reported assessments obtained, the PP intervention resulted in improvements in the resilience scale (mean difference, 2.4 ± 5.4; P = .03). From unstructured qualitative interviews, participants reported the PP exercises and intervention helped them to focus on positive emotions and the group format fostered a sense of community and social support. An 8-week phone-delivered group format PP intervention is feasible and acceptable in HSCT survivors. The piloted intervention could be tested with minor modifications in a randomized study to definitively examine the impact of the group format PP intervention on health-related outcomes.