Pre-Transplant Platelet Refractoriness and Alternative Donors Are Associated With Cytomegalovirus Retinitis in Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia.

Yuehong Zhang,Ling Li,Wenjian Mo,Xu Zhang,Zongyin Gao,Yuqin Liang,Shunqing Wang,Jinpeng Cao

doi:10.3389/fcimb.2022.870296

Abstract

BackgroundCytomegalovirus retinitis is a severe, vision-threatening opportunistic infection in an immunodeficient population. Reports on cytomegalovirus retinitis in hematopoietic stem cell transplant recipients due to severe aplastic anemia have been scant. This study assessed the risk of cytomegalovirus retinitis in relation to the pre-transplant status of severe aplastic anemia patients.MethodsWe conducted a retrospective nested case-control study of cytomegalovirus retinitis among severe aplastic anemia patients receiving allogeneic hematopoietic stem cell transplants in a tertiary care institution that attends severe aplastic anemia patients from southern China from January 1, 2013 to December 31, 2018. Each cytomegalovirus retinitis case was matched with four controls without cytomegalovirus retinitis by age and gender. Thirteen pre-transplant parameters were chosen to compare the risk factor levels between the cases and controls. Multivariable logistic regressions were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs).ResultsA total of 361 severe aplastic anemia patients received hematopoietic stem cell transplants in the study period 2013–2018 in our medical institution, and 31 (8.58%) developed cytomegalovirus retinitis. Cytomegalovirus retinitis was diagnosed in the median of 148 days after transplantation. We confirmed platelet refractoriness more frequently in cases than in controls (p = 0.0005). Compared with human leukocyte antigen-matched sibling donors, alternative donors were significantly more prone to cytomegalovirus retinitis (p = 0.0009). After stepwise selection in multivariate logistic regression, platelet refractoriness (OR 5.41, 95% CI 1.98–15.39), haploidentical donor (OR 7.46, 95% CI 2.19–34.87), and unrelated donor (OR 8.38, 95% CI 2.30–41.34) were associated with an increased risk of cytomegalovirus retinitis.ConclusionsPre-transplant platelet refractoriness and alternative donors were significant predictors of cytomegalovirus retinitis in severe aplastic anemia recipients. These results highlight the importance of accounting for existing risks while developing prevention strategies and preemptive treatment for severe aplastic anemia recipients. We recommend that the platelet count be closely monitored and thrombopoietin be properly applied during the period when cytomegalovirus retinitis is prone to occur.

Highlights

Cytomegalovirus (CMV) is a double-stranded DNA virus of the herpes family
The points of the two variables were added to the total points. In this case-control study of Severe aplastic anemia (SAA) hematopoietic stem cell transplantation (HSCT) recipients, two pretransplant variables—platelet refractoriness and alternative donors—proved to be risk factors for CMV retinitis (CMVR). This is the first time these two risk factors have been reported in SAA HSCT recipients
Our findings are helpful in guiding clinical decisions about reducing the risk of CMVR and maximizing the benefits of HSCT in SAA patients as part of universal prevention strategies targeting post-transplant CMVR

Summary

Introduction

Cytomegalovirus (CMV) is a double-stranded DNA virus of the herpes family. CMV infection can be a primary infection, reinfection, or reactivation. CMV retinitis (CMVR), a progressive retinal necrotizing disease, is an ocular opportunistic infection in patients who cannot produce effective immune response to CMV, which mainly occurs in patients with human immunodeficiency virus infection, immunosuppressive therapy and organ transplant (Munro et al, 2019; Stern et al, 2019). Severe aplastic anemia (SAA) is a progressive autoimmune disease characterized by peripheral pancytopenia and marrow hypoplasia, which can be treated effectively with allogeneic hematopoietic stem cell transplantation (HSCT) (Bacigalupo, 2017; Kumar et al, 2017). Many studies on CMVR in non-human immunodeficiency virus individuals have focused on HSCT recipients with malignant hematological diseases (Ando et al, 2020). Reports on cytomegalovirus retinitis in hematopoietic stem cell transplant recipients due to severe aplastic anemia have been scant. This study assessed the risk of cytomegalovirus retinitis in relation to the pretransplant status of severe aplastic anemia patients

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Results

Conclusion