ABSTRACT
BACKGROUND: Trans-acting programmed death-ligand 1 (PD-L1) derives from malignant cells in three known forms. High levels of secreted splice variant PD-L1 (sPD-L1), ADAM10/ADAM17-shed sPD-L1, and PD-L1-positive extracellular vesicles (evPD-L1) each predict poor prognosis and limited response to PD-(L)1 checkpoint inhibitors in cancer. To our knowledge, no clinical intervention has reduced any of these circulating forms of extracellular PD-L1. Here, we explore therapeutic plasma exchange (TPE) as a treatment to reduce circulating extracellular PD-L1. RESULTS: In patients with melanoma, sPD-L1 levels above 0.277 ng/mL predicted inferior overall survival. In patients undergoing TPE for non-malignant indications, each TPE session removed a mean 70.8% sPD-L1 and 73.1% evPD-L1 detectable in plasma. TPE also reduced total and ADAM10-positive extracellular vesicles. CONCLUSION: Here, we report the first known clinical intervention to remove either sPD-L1 or evPD-L1 from plasma in vivo. TPE reduces plasma sPD-L1 and evPD-L1 in vivo and may have a role in treatment with immunotherapy. TPE may also prove useful in patients with other extracellular vesicle-related conditions.
Subject(s)
B7-H1 Antigen/immunology , Extracellular Vesicles/immunology , Immunotherapy/methods , Plasma Exchange/methods , Adult , Aged , Female , Humans , Male , Middle AgedABSTRACT
BACKGROUND: A new protocol has been developed on the Amicus Separator that enables the device to perform online extracorporeal photopheresis (ECP) procedures when used in conjunction with the Phelix photoactivation device and associated disposable kit. The objective of this study was to evaluate the safety and performance of the Amicus ECP System in adult subjects with steroid-refractory or dependent chronic graft vs host disease (cGVHD). STUDY DESIGN AND METHODS: Eight subjects with mild to severe cGVHD underwent 31 procedures. Subject safety evaluations were performed pre and post procedure and adverse events (AEs) were recorded during treatment and 24 hours after the last procedure. In vitro evaluations of the treated cells included hematology counts and lymphocyte apoptosis, viability and proliferation as measures for ECP procedure validation. RESULTS: For n = 23 evaluable procedures, median (range) procedure time was 88 (78-110) minutes, during which 2.9 (0.6-4.7) × 109 TNCs (approximately 90% MNCs) were treated and reinfused to the subjects. All subject safety evaluations (vitals, cell counts, plasma hemoglobin and bacterial and endotoxin testing) were within expected ranges. All device or procedure related AEs were mild in nature. After 24 hours in culture, 86 (52-98)% of treated lymphocytes were apoptotic compared to 27 (15-51)% in controls. Inhibition of lymphocyte proliferation was >91% in all procedures. CONCLUSION: ECP procedures were safely completed in adult subjects with SR-cGVHD treated using the new online Amicus ECP system.
Subject(s)
Graft vs Host Disease/therapy , Photopheresis/methods , Steroids/therapeutic use , Adult , Aged , Apoptosis , Cell Proliferation , Cell Survival , Female , Glomerular Filtration Rate , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , In Vitro Techniques , Internet , Lymphocytes/cytology , Male , Middle Aged , Patient Safety , Photochemistry , Pilot Projects , Risk , Treatment OutcomeABSTRACT
Palliative care (PC) is perhaps the most inherently interdisciplinary specialty within health care. Comprehensive PC is delivered by a core team of physicians, nurses, social workers, spiritual care providers, pharmacists, and others who address the broad range of medical, psychosocial, and spiritual needs of those living with serious illness. While PC clinicians are typically skilled in screening for distress, the best path to follow when patients screen positive for psychosocial distress or exhibit mental health challenges may not always be clear. This article brings together the perspectives of experienced social workers practicing across PC and hospice settings. It seeks to identify opportunities and rationale for the integration of palliative social work (PSW) in the provision of quality, person-centered, family-focused, and culturally congruent care for the seriously ill. Increasing recognition of the impact of social determinants of health highlights the critical importance of including PSW if we are to better understand and ultimately address the broad range of factors that influence people's quality of life.
Subject(s)
Hospice Care , Hospice and Palliative Care Nursing , Humans , Palliative Care , Quality of Life , Social WorkABSTRACT
Many of America's Veterans have unique medical and psychosocial needs related to their military service. Since most medical care received by Veterans occurs outside of the Department of Veterans Affairs (VA) health care system, it is imperative that all medical providers have a working understanding of the unique needs of Veterans and some of the many programs and services available to Veterans through the VA. This article, created by an interdisciplinary team of palliative care and hospice providers who care for Veterans throughout the country, seeks to improve the comfort with which non-VA clinicians care for Veterans while increasing knowledge about programs for which Veterans might qualify through the VA.
