A Critical Analysis of the Delivery of a Psychosocial Workshop for Cancer Survivors with Lymphedema

Secondary lymphedema is a chronic condition that can develop after the treatment of cancer and can often lead to negative psychological and social impairments. When dealing with chronic illness, hoping and coping are interdependent. Previous research has assessed the outcomes of workshops designed to enhance hope but has not examined the workshop itself to determine how those outcomes were achieved. This study deconstructs the Living Hopefully with Lymphedema workshop to identify (1) what aspects of the workshop facilitated or interfered with therapeutic progress, (2) key aspects of facilitation that contributed to the functioning of the workshop, and (3) how participants responded to the workshop. Two three-day workshops were attended by a total of 19 participants. All sessions were audio taped and the recordings analyzed. Theoretical coding revealed a central theme focused on the importance of a safe environment within the workshop. Facilitators and participants worked together to co-create, maintain, and protect a safe space in which to engage in therapy. Findings are discussed in relation to key aspects of facilitation and the participants’ response to the workshops. Recommendations for future workshop development are presented

Promoting regulation via the inhibition of DNAM-1 after transplantation

Donor T cells play pivotal roles in graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effects following bone marrow transplantation (BMT). DNAX accessory molecule 1 (DNAM-1) is a costimulatory and adhesion molecule, expressed mainly by natural killer cells and CD8(+) T cells at steady state to promote adhesion to ligand-expressing targets and enhance cytolysis. We have analyzed the role of this pathway in GVHD and GVL. The absence of DNAM-1 on the donor graft attenuated GVHD in major histocompatibility complex (MHC)-mismatched and MHC-matched BMT following conditioning with lethal and sublethal irradiation. In contrast, DNAM-1 was not critical for GVL effects against ligand (CD155) expressing and nonexpressing leukemia. The effects on GVHD following myeloablative conditioning were independent of CD8(+) T cells and dependent on CD4(+) T cells, and specifically donor FoxP3(+) regulatory T cells (T-reg). The absence of DNAM-1 promoted the expansion and suppressive function of T-reg after BMT. These findings provide support for therapeutic DNAM-1 inhibition to promote tolerance in relevant inflammatory-based diseases characterized by T-cell activation

Soluble lymphotoxin is an important effector molecule in GVHD and GVL

Tumor necrosis factor (TNF) is a key cytokine in the effector phase of graft-versus-host disease (GVHD) after bone marrow transplantation, and TNF inhibitors have shown efficacy in clinical and experimental GVHD. TNF signals through the TNF receptors (TNFR), which also bind soluble lymphotoxin (LT alpha 3), a TNF family member with a previously unexamined role in GVHD pathogenesis. We have used preclinical models to investigate the role of LT in GVHD. We confirm that grafts deficient in LT alpha have an attenuated capacity to induce GVHD equal to that seen when grafts lack TNF. This is not associated with other defects in cytokine production or T-cell function, suggesting that LT alpha 3 exerts its pathogenic activity directly via TNFR signaling. We confirm that donor-derived LT alpha is required for graft-versus-leukemia (GVL) effects, with equal impairment in leukemic clearance seen in recipients of LT alpha- and TNF-deficient grafts. Further impairment in tumor clearance was seen using Tnf/Lta(-/-) donors, suggesting that these molecules play nonredundant roles in GVL. Importantly, donor TNF/LT alpha were only required for GVL where the recipient leukemia was susceptible to apoptosis via p55 TNFR signaling. These data suggest that antagonists neutralizing both TNF and LT alpha 3 may be effective for treatment of GVHD, particularly if residual leukemia lacks the p55 TNFR. (Blood. 2010;115:122-132