Reactivation and dynamics of cytomegalovirus and Epstein‐Barr virus after rabbit antithymocyte globulin and cyclosporine for aplastic anemia

Park, Sung‐Soo; Cho, Sung‐Yeon; Han, Eunhee; Min, Gi June; Park, Silvia; Yoon, Jae‐Ho; Lee, Sung‐Eun; Cho, Byung‐Sik; Eom, Ki‐Seong; Kim, Yoo‐Jin; Lee, Seok; Kim, Sang-Yong; Min, Chang‐Ki; Cho, Seok Goo; Lee, Jong Wook

doi:10.1111/ejh.13308

Cited by 5 publications

(5 citation statements)

References 42 publications

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“…In previous studies, severe aplastic anemia (SAA) patients undergoing unrelated donor transplantation received rituximab in combination with ATG-containing conditioning regimens to prevent EBV reactivation ( 27 , 48 ). Previous studies showed that the risk factors for EBV activation were predominantly related to the degree of T cell depletion or impairment, including mismatch between donor and recipient, T cell depletion from graft, degree and duration of immunosuppression, and use of ATG or alemtuzumab (anti-CD52) ( 41 , 45 , 49 – 51 ). Furthermore, we found CMV activation, HLA mismatch and cGVHD were independent risk factors for EBV reactivation, while the usage of rituximab was proved to prevent EBV reactivation.…”

Section: Discussionmentioning

confidence: 99%

The impact of Rituximab administered before transplantation in patients undergoing allogeneic hematopoietic stem cell transplantation: A real-world study

et al. 2022

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Rituximab is used to eliminate B cells as a chimeric monoclonal antibody directed against CD20, a B-cell antigen expressed on B cells. To explore the impact of rituximab administered before transplantation, we implemented a retrospective, monocentric study and utilized real-world data collected at our center between January 2018 and December 2020, and then followed until December 2021. Based on whether a dose of 375mg/m2 rituximab was used at least once within two weeks before transplantation, patients undergoing allo-HSCT were classified into two groups: rituximab (N=176) and non-rituximab (N=344) group. Amongst all the patients, the application of rituximab decreased EBV reactivation (P<0.01) and rituximab was an independent factor in the prevention of EBV reactivation by both univariate and multivariate analyses (HR 0.56, 95%CI 0.33-0.97, P=0.04). In AML patients, there were significant differences in the cumulative incidence of aGVHD between the two groups (P=0.04). Our data showed that rituximab was association with a decreased incidence of aGVHD in AML patients according to both univariate and multivariate analyses. There was no difference between the two groups in other sets of populations. Thus, our study indicated that rituximab administered before transplantation may help prevent EBV reactivation in all allo-HSCT patients, as well as prevent aGVHD in AML patients after allo-HSCT.

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Section: Discussionmentioning

confidence: 99%

The impact of Rituximab administered before transplantation in patients undergoing allogeneic hematopoietic stem cell transplantation: A real-world study

et al. 2022

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“…A partial response was determined as no longer meeting the criteria for SAA and having transfusion independence for >8 weeks 3 , 14 . An analysis of glycosylphosphatidylinositol‐deficient granulocytes was performed by flow cytometry outlined in our previous report 13 . Bone marrow samples of healthy controls were collected from healthy donor for allogeneic BM transplantation following written consent.…”

Section: Methodsmentioning

confidence: 99%

“…The diagnosis and severity of idiopathic AA were assessed according to previous reports. 10 , 11 Patients received IST consisting of rabbit ATG (Thymoglobulin; Genzyme-Sanofi, Lyon, France) and cyclosporine (n = 7) as previously described 12 , 13 or cyclosporine monotherapy (n = 4). Patients with SAA received the combination of ATG and cyclosporine as the standard treatment.…”

Section: Methodsmentioning

confidence: 99%

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Single-cell RNA Sequencing Reveals Novel Cellular Factors for Response to Immunosuppressive Therapy in Aplastic Anemia

Jang,

Kim,

Park

et al. 2023

HemaSphere

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Aplastic anemia (AA) is a lethal hematological disorder; however, its pathogenesis is not fully understood. Although immunosuppressive therapy (IST) is a major treatment option for AA, one-third of patients do not respond to IST and its resistance mechanism remains elusive. To understand AA pathogenesis and IST resistance, we performed single-cell RNA sequencing (scRNA-seq) of bone marrow (BM) from healthy controls and patients with AA at diagnosis. We found that CD34+ early-stage erythroid precursor cells and PROM1+ hematopoietic stem cells were significantly depleted in AA, which suggests that the depletion of CD34+ early-stage erythroid precursor cells and PROM1+ hematopoietic stem cells might be one of the major mechanisms for AA pathogenesis related with BM-cell hypoplasia. More importantly, we observed the significant enrichment of CD8+ T cells and T cell–activating intercellular interactions in IST responders, indicating the association between the expansion and activation of T cells and the positive response of IST in AA. Taken together, our findings represent a valuable resource offering novel insights into the cellular heterogeneity in the BM of AA and reveal potential biomarkers for IST, building the foundation for future precision therapies in AA.

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“…In addition, the use of ATG [39], a higher titer of CMV-IgG in recipients before allo-HSCT [40], and the titer of the human leukocyte antigen allele type [41] have also been associated with CMV reactivation. ATG use or dose may increase CMV reactivation in patients with aplastic anemia and renal transplantation [42][43][44][45]. More aggressive CMV prophylaxis, such as letermovir, should be considered in patients with these risk factors, which present before allo-HSCT or may occur during allo-HSCT.…”

Section: Plos Onementioning

confidence: 99%

Cytomegalovirus reactivation under pre-emptive therapy following allogeneic hematopoietic stem cell transplant: Pattern, survival, and risk factors in the Republic of Korea

Kang,

Jeon,

et al. 2023

PLoS ONE

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Introduction Pre-emptive therapy for cytomegalovirus (CMV) reactivation has been used in allogeneic hematopoietic stem cell transplantation (allo-HSCT). It is unclear if this strategy has poorer clinical outcomes in CMV-endemic areas and if more aggressive prophylaxis is required. Methods We retrospectively analyzed the patterns and survival after CMV reactivation in patients undergoing pre-emptive therapy following allo-HSCT and assessed high-risk patients who could benefit from aggressive CMV prophylaxis in endemic areas. Results Of the 292 patients who underwent allo-HSCT, 70.5% (donor+ or recipient+) were CMV seropositive. CMV reactivation occurred in 139 patients (47.6%), with a median of 31.5 days from day 0 of allo-HSCT. The overall survival of patients with CMV reactivation who received pre-emptive therapy did not differ from those without reactivation. Of the 139 patients with CMV reactivation, 78 (56.1%) underwent ≥2 rounds of pre-emptive therapy. In multivariate analysis, the risk of CMV reactivation was higher in patients with multiple myeloma, with CMV seropositivity of the recipient and donor, administered with a higher dose of anti-thymocyte globulin (ATG), and with acute graft-versus-host disease (aGVHD) ≥ grade 2. Conclusion Although half of the patients with allo-HSCT were administered with pre-emptive therapy for CMV, CMV reactivation did not affect their survival, indicating the advantages of pre-emptive therapy, even in CMV-endemic areas. The cost-effectiveness of more aggressive CMV prophylaxis should be re-evaluated in patients at a high risk for CMV reactivation.

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Reactivation and dynamics of cytomegalovirus and Epstein‐Barr virus after rabbit antithymocyte globulin and cyclosporine for aplastic anemia

Cited by 5 publications

References 42 publications

The impact of Rituximab administered before transplantation in patients undergoing allogeneic hematopoietic stem cell transplantation: A real-world study

The impact of Rituximab administered before transplantation in patients undergoing allogeneic hematopoietic stem cell transplantation: A real-world study

Single-cell RNA Sequencing Reveals Novel Cellular Factors for Response to Immunosuppressive Therapy in Aplastic Anemia

Cytomegalovirus reactivation under pre-emptive therapy following allogeneic hematopoietic stem cell transplant: Pattern, survival, and risk factors in the Republic of Korea

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