Khulud Alanazi

Background Cytomegalovirus (CMV) infection is a major contributor to morbidity and mortality in recipients of hematopoietic stem cell transplant (HSCT), solid organ transplant (SOT), and chimeric antigen receptor T-cell (CAR-T) therapy. While antiviral agents remain the cornerstone of treatment, CMV-specific immunoglobulins (CMVIG) have been utilized as adjunct therapy with variable outcomes. This study aims to evaluate the virological response and tolerability of CMVIG in cases of severe or refractory CMV viremia, with or without CMV disease. Methods: We conducted a single-center retrospective case series of adult recipients of SOT, allogeneic HSCT, and/or CAR-T cell therapy who developed CMV viremia or disease and received at least one dose of CMVIG between May 2017 and May 2023 at our center. Virological improvement within 14 days of starting CMVIG and tolerability of CMVIG are the primary outcome of this study. Results: A total of 33 patients were included. Of these, 29 underwent transplantation [SOT: 48.2%, HSCT: 51.7%], and five underwent CAR-T cell therapy (one post-HSCT). High-risk CMV serostatus was present in 12%. CMV viremia was documented in 32 patients (97%), and tissue-invasive disease was present in 11 patients (33.3%). Virological response, was observed in 65.6% of the cohort. The median time to undetectable CMV viral load following CMVIG initiation was 28 days. CMVIG was well-tolerated. All-cause mortality at 90 days remained high (57%). Conclusion: In this case series, CMVIG demonstrated a virological response rate of 65.6% in patients with severe or refractory CMV infection. While CMVIG was well-tolerated with minimal adverse events, the high mortality rate despite virological response suggests that CMVIG may be insufficient for this critically ill population. Our findings should be interpreted as observational data from a small case series, and prospective controlled trials are needed to establish the true benefit of CMVIG in combination with standard antiviral therapy.

Background: Data about the impact of albumin-to-alkaline phosphatase ratio (AAPR) on prognosis in hepatocellular cancer (HCC) patients are inconclusive and conflicting. Methods: The authors systematically searched literatures from seven databases (PubMed, Medline, Web of Science, Cochrane Library, Embase, Google Scholar, and CINAHL), updated to September 2023. Hazard ratios (HRs) and 95% CIs were pooled and synthesized using Comprehensive Meta-Analysis version 3 in order to assess the overall impact of AAPR on patient’s prognosis. Results: In total, 8 studies involving 13 cohorts with 3774 cases were included. Pooled results from both univariate and multivariate analyses revealed that higher AAPR was an independent prognostic factor for overall survival (HR=0.429, 95% CI: 0.361–0.509, P=0.001; HR=0.476, 95% CI: 0.421–0.538, P=0.001; respectively). Similarly, pooled multivariate results showed that higher AAPR was associated with better disease-free survival (HR=0.558, 95% CI: 0.452–0.688, P=0.001). Moreover, pooled results from both univariate and multivariate analyses revealed that higher AAPR was an independent prognostic factor for recurrence-free survival (HR=0.540, 95% CI: 0.420–0.694, P=0.001; HR=0.647, 95% CI: 0.494–0.848, P=0.002; respectively). Subgroups analysis showed that elevated AAPR still significantly correlated with better overall survival across the confounding factors. Moreover, sensitivity analysis suggested the robustness of these findings and no publication bias was detected. Conclusions: In summary, higher AAPR could be considered as a reliable prognostic factor in patients with HCC, which could be used as a routine inspection of HCC patients to individualized prognosis prediction and clinical decision making.