Negative Impact of Cytomegalovirus Reactivation on Survival in Adult Patients with Aplastic Anemia after an Allogeneic Hematopoietic Stem Cell Transplantation: A Report from Transplantation-Related Complication and Adult Aplastic Anemia Working Groups of the Japan Society for Hematopoietic Cell Transplantation

Abstract

Cytomegalovirus (CMV) infection is a major infectious complication following an allogeneic hematopoietic stem cell transplantation (allo-HSCT). Recent large-scale retrospective studies reported that CMV reactivation is an independent risk factor for poor post-transplant outcomes, although the development of CMV end-organ disease is suppressed by the CMV antiviral preemptive therapy, which has been mainly analyzed for hematopoietic malignancies, such as acute leukemia. However, it remains unclear whether CMV reactivation also has a negative effect on post-transplant outcomes in aplastic anemia (AA). Therefore, we evaluated the clinical relevance of CMV reactivation in patients with AA using the registry database of the Japan Society for Hematopoietic Cell Transplantation. Adult patients with AA who underwent their first allo-HSCT between 2005 and 2017 and who survived with neutrophil engraftment until 100 days post-transplantation were analyzed (n = 672). Patients were monitored using pp65 antigenemia since the time of engraftment, and CMV reactivation in the analysis of this study was defined as the beginning of CMV preemptive or definitive therapy within 100 days post-transplantation. CMV reactivation occurred in 372 (55%) patients, including 19 with CMV end-organ disease. In time-dependent multivariate analysis, patients aged ≥40 years (hazard ratio [HR], 1.89; P = .003) who underwent transplantation from HLA-matched related peripheral blood stem cells (HR, 2.85; P = .008), HLA-matched unrelated bone marrow (BM) (HR, 2.01; P = .036), and other stem cell sources (HR, 2.32; P = .007) compared to HLA-matched related BM, CMV reactivation (HR 1.65; P = .042), grade II to IV acute graft-versus-host disease (HR 1.73; P = .013), and secondary graft failure (HR 7.09; P < .001) had independent risk factors that significantly decreased overall survival, indicating that CMV reactivation, one of the early events at post-transplantation, had a significant negative impact on the long-term prognosis at post-transplantation. This effect was more pronounced in patients aged ≥40 years who received a graft from other than HLA-matched related BM. Comparing the causes of death with and without CMV reactivation, no significant difference in the frequency of each cause of death was observed between the 2 groups (P = .453). Improvement of post-transplant CMV management that effectively suppresses CMV reactivation in the early stage at post-transplantation will be required to improve post-transplant outcomes, especially in high-risk patients.

Keywords: Allogeneic hematopoietic stem cell transplantation; Aplastic anemia; Cytomegalovirus; Survival.