Cytomegalovirus (CMV) infection and primary disease relapse remain challenging problems after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We sought to assess the association between CMV infection and disease relapse after transplantation. PubMed, EMBASE, the Cochrane Library, SCI, and Chinese Biomedicine Databases were searched up to July 1, 2018, for all studies that investigate pre-transplant CMV serostatus, CMV replication, and primary disease relapse in allo-HSCT patients with hematologic malignancies. Meta-analysis of 24 eligible cohort studies showed a significantly lower relapse risk after allo-HSCT in patients with CMV replication in acute myeloid leukemia (AML) (HR = 0.64, 95% CI, 0.50-0.83; P < 0.001) subgroup. However, CMV replication was associated with increased non-relapse mortality (NRM) in AML patients (HR = 1.64, 95% CI, 1.46-1.85; P < 0.001), but not associated with overall survival (OS) or graft-versus-host disease for AML patients (P > 0.05). There was no association between pre-transplant CMV serostatus and disease relapse, although D-/R- was associated with better OS in acute leukemia patients (HR = 0.89, 95% CI, 0.83-0.96; P = 0.003). In AML patients, CMV replication may be a protective predictor against disease relapse, although the potential benefit of CMV replication is offset by increased NRM.

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