Incidence, Patterns, and Outcomes of Fungal Infections in Patients With Graft Versus Host Disease Requiring Systemic Steroids Following Allogeneic Hematopoietic Cell Transplantation: A Systematic Review and Meta Analysis.

BACKGROUND: Graft-versus-host disease (GVHD) is a significant complication following allogeneic hematopoietic cell transplantation (HCT). Systemic corticosteroids, the standard treatment for GVHD, increase susceptibility to infections, including invasive fungal infections (IFIs). This study aimed to systematically review and meta-analyze existing literature to assess the incidence, patterns, and outcomes of IFIs in this high-risk population. METHODS: A systematic literature search was conducted in PubMed, EMBASE, Scopus, and the Cochrane Library, following the PRISMA guidelines. Four eligible studies were included reporting IFI in GVHD following HCT. A pooled analysis of proportions with 95% confidence intervals (CIs) was conducted using the 'meta' package in R version 4.4. RESULTS: A total of 1,141 patients with GVHD post-HCT were included. The pooled overall incidence of IFIs was 8.0% (95% CI: 6.0%-10.0%; I² = 49.5%). Aspergillosis was the most reported fungal infection, with a pooled incidence of 5% (95% CI: 3.0%-.9.0.%; I² = 70.3%) Among patients with acute GVHD, the pooled incidence of IFIs was 10.0% (95% CI: 8.0%-13.0%; I² = 0%)., while in chronic GVHD it was 9.0% (95% CI: 4.0%-17.0%; I² = 83.7%). The cumulative incidence of IFIs at 100 days post-transplant was 7.0% (95% CI: 5.0%-13.0%; I² = 73.0%). Pooled overall IFI-related mortality in the entire cohort was estimated at 3% (95% CI: 2.0%-4.0%; I² = 0.0%) Pooled IFI-related mortality among established or probable IFIs patients was 39.4% (95% CI: 25.5%-55.3%), with subgroup analysis revealing higher mortality in studies with ≥12 months of follow-up compared to those with <12 months (4% vs. 3%). Overall survival (OS) at 100 days ranged from 64% to 82% (I² = 97.4%). Patients receiving azole-based prophylaxis had a pooled IFI incidence of 7.0% (95% CI: 5.0%-10.0%; I² = 0%), compared to 9.0% (95% CI: 6.0%-14.0%; I² = 38%, P = .151) in those receiving combination antifungal prophylaxis. CONCLUSION: Invasive fungal infections remain a significant complication in patients with GVHD after transplant, particularly among those with acute GVHD and longer follow-up. Despite antifungal prophylaxis, IFI-related mortality persists, underscoring the need for improved preventive strategies.