Risk factors for invasive fungal infections after hematopoietic stem cell transplantation: a systematic review and meta-analysis

Background Invasive fungal infections (IFIs) are a common infectious complications after hematopoietic stem cell transplantation (HSCT), seriously threatening the survival of patients. Objectives This systematic review aimed to investigate risk factors associated with IFIs following HSCT. Data sources Pubmed, EMBASE, Web of Science, and the Cochrane Library until April 2023. Study eligibility criteria Case-control or cohort studies that assessed risk factors for IFIs among HSCT recipients were included. Methods Two authors independently conducted the selection of studies and extraction of data. Risk factors for IFIs, invasive aspergillosis (IA)/invasive mold infections (IMIs) and invasive candida infection after HSCT were compiled separately by meta-analysis using RevMan 5.4 and R language 4.1.2. Results Out of 1637 studies screened, 51 studies involving 109,155 patients were included, with 45 studies providing adequate data for meta-analysis. Identified risk factors for IFIs included prolonged neutropenia, intensified therapy for graft-versus-host disease (GVHD), prior transplantation, prior proven/probable IFI, acute GVHD≥grade II, extensive/severe chronic GVHD, use of anti-thymocyte globulin (ATG) during transplantation, haploidentical transplantation, high-dose glucocorticoids, Epstein-Barr virus (EBV) infection, cytomegalovirus (CMV) infection/reactivation, and lower albumin. Conversely, antifungal prophylaxis emerged as the sole preventive factor. For IA/IMIs, top risk factors were extensive/severe chronic GVHD, respiratory viral infection, high-dose glucocorticoids, acute GVHD≥grade II, and human leukocyte antigen (HLA) mismatch. Cord blood transplantation was the sole significant risk factor for invasive candidiasis. Nevertheless, there was likely a high degree of interdependence among various risk factors. Conclusion This meta-analysis provides a thorough review of risk factors for IFIs infection after HSCT. The achieved insights can aid in stratifying patients who are at an elevated risk of IFIs, promoting antifungal preventive strategies.