OBJECTIVES: Chronic graft-versus-host disease (cGVHD) is major long-term complication of allogeneic hematopoietic stem cell transplantation (HSCT). This study aimed to perform a systematic literature review of the evidence on cGVHD incidence, disease severity and affecting factors.

METHODS: A systematic review of English-language articles published between 2007 and 2017 was conducted using PubMed. Literature search was limited to studies that applied the 2005 or 2014 National Institute of Health Consensus Criteria for the diagnosis and staging of cGVHD, and had a cohort size of at least 100 patients. Studies were assessed for quality. Data on the cumulative incidence of cGVHD and related disease severity, and their predictive factors were extracted.

RESULTS: After full text screening 84 articles were included. The 1-, 2-, and 5-year cumulative incidence of cGVHD ranged from 14% to 60%, from 6% to 90%, and from 44% to 70%, respectively. Based on reviewed articles, age, gender, donor type, type of conditioning regimen, type of cGVHD prophylaxis, stem cell source, prior aGVHD, underlying disorders and immune system related factors (e.g. number of CD34+ cells or late activated T-cells) were predictors significantly affecting cGVHD. The 1-, 2-year cumulative incidence of moderate to severe cGVHD ranged from 8.6% to 42.6% and from 3.2% to 56.5%, respectively, while the 1-, 2-year cumulative incidence of severe cGVHD ranged from 2.2% to 13% and from 2.4% to 31.2%, respectively. The distribution of moderate and severe cGVHD patients among diagnosed cGVHD patients ranged from 15% to 84% and from 4% to 66%, respectively.

CONCLUSIONS: cGVHD is a highly prevalent disorder in HSCT recipients. The high number of influencing parameters may explain the wide variation of observed cGVHD cumulative incidence. Most studies focused on the factors affecting cGVHD incidence; however, more evidence is needed on the predictors of disease severity.