Red blood cell transfusion in myelodysplastic syndromes: A systematic review.

Patients with myelodysplastic syndrome (MDS) frequently receive red blood cell (RBC) transfusions for anaemia resulting from ineffective erythropoiesis. While RBC transfusions may rapidly increase haemoglobin values, their impact on clinical and health services outcomes in MDS patients has not previously been summarized. We conducted a systematic review of the literature to evaluate risks and benefits of RBC transfusions in MDS patients. We searched electronic databases (MEDLINE, Embase, CENTRAL, CINAHL) from inception through June 4, 2021 to identify studies reporting data on RBC transfusions in MDS patients. Full text publications that assessed RBC transfusions as an intervention and reported at least one clinical, laboratory, or healthcare outcome associated with transfusion were included. Study characteristics, transfusion information and transfusion-related outcomes were extracted and reported. We identified 1243 original studies, of which 38 met eligibility requirements and were included. Fourteen reported on survival following diagnosis of MDS, with the majority reporting poorer survival among patients receiving or requiring more frequent transfusions. Nine reported on transfusion-related iron overload and its complications. Other outcomes included rates of allo/autoimmunization and adverse transfusion reactions, and healthcare costs incurred by patients with a greater transfusion burden. Only two studies reported on symptom relief following transfusion. This review underscores transfusion dependence as a negative prognostic factor for MDS patients and highlights the paucity of evidence surrounding quality of life and symptom-related outcomes following RBC transfusions in this population. Further study of patient-important outcomes associated with transfusion in MDS patients is warranted to improve therapeutic recommendations and inform resource allocation.

Direct-Acting Antiviral Treatment of HCV Infection Does Not Resolve the Dysfunction of Circulating CD8+ T-Cells in Advanced Liver Disease.

Chronic hepatitis C virus (HCV) infection disrupts immune functions, including that of cytotoxic CD8+ T-cells which are important mediators of immune response. While HCV cure aims to eliminate long term sequelae of infection, whether direct-acting antiviral (DAA) treatment results in immune reconstitution remains unclear. We and others have reported generalized CD8+ T-cell dysfunction in chronic HCV infection and our research suggests that the degree of liver damage is a factor in this process. Our recent research indicates that liver fibrosis is not readily reversed after DAA-mediated clearance of chronic HCV infection. We therefore examined the function of circulating CD8+ T-cell subsets in chronic HCV infection in the context of liver fibrosis severity, determined by ultrasound elastography and Metavir F-score system. We observed progressive shifts in CD8+ T-cell subset distribution in HCV-infected individuals with advanced liver fibrosis (F4) compared to minimal fibrosis (F0-1) or uninfected controls, and this remained unchanged after viral cure. Impaired CD8+ T-cell function was observed as a reduced proportion of CD107+ and perforin+ late effector memory cells in HCV+(F4) and HCV+(F0-1) individuals, respectively. In HCV+(F4) individuals, nearly all CD8+ T-cell subsets had an elevated proportion of perforin+ cells while naïve cells had increased proportions of IFN-γ+ and CD107+ cells. These exaggerated CD8+ T-cell activities were not resolved when evaluated 24 weeks after completion of DAA therapy and HCV clearance. This was further supported by sustained, high levels of cell proliferation and cytolytic activity. Furthermore, DAA therapy had no effect on elevated concentrations of systemic inflammatory cytokines and decreased levels of inhibitory TGF-ß in the plasma of HCV+(F4) individuals, suggesting HCV infection and advanced liver disease result in a long-lasting immune activating microenvironment. These data demonstrate that in chronic HCV infection, liver fibrosis severity is associated with generalized hyperfunctional CD8+ T-cells, particularly with perforin production and cytotoxicity, and this persists after viral clearance. Whether DAA therapy will eliminate other related long-term sequelae in HCV+(F4) individuals remains an important research question.