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

Abstract

Background: Invasive fungal infections (IFIs) are common infectious complications after haematopoietic stem cell transplantation (HSCT), seriously threatening the survival of patients.

Objectives: This systematic review aimed to investigate risk factors associated with IFIs following HSCT.

Methods: Two authors independently conducted the selection of studies and extraction of data. Risk factors for IFIs, invasive aspergillosis or invasive mould infections and invasive candida infection after HSCT were compiled separately by meta-analysis using RevMan 5.4 and R language 4.1.2.

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.

Participants: Patients experiencing HSCT.

Test/s: None.

Reference standard: The IFIs were defined according to the European Organisation for Research and Treatment of Cancer/Mycosis Study Group (EORTC/MSG) criteria, or a similar definition.

Assessment of risk of bias: A modified version of the Newcastle-Ottawa Scale was used.

Methods of data synthesis: A random-effects model with the Mantel-Haenszel method was used to pool results from primary studies.

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), previous transplantation, previous proven or probable IFI, acute GVHD ≥ grade II, extensive or severe chronic GVHD, use of anti-thymocyte globulin during transplantation, haploidentical transplantation, high-dose glucocorticoids, Epstein-Barr virus infection, cytomegalovirus infection or reactivation, and lower albumin. Conversely, antifungal prophylaxis emerged as the sole preventive factor. For invasive aspergillosis or invasive mould infections, the top risk factors were extensive or severe chronic GVHD, respiratory viral infection, high-dose glucocorticoids, acute GVHD ≥ grade II, and human leukocyte antigen mismatch. Cord blood transplantation was the sole significant risk factor for invasive candidiasis. However, there was likely a high degree of interdependence among various risk factors.

Discussion: 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 and promoting antifungal preventive strategies.

Keywords: Clinical research; Haematopoietic stem cell transplantation; Invasive fungal infections; Meta analysis; Risk factors.