Efficacy of Low-Dose Rituximab as Preemptive Treatment of EBV DNA-emia After Allogeneic Hematopoietic Stem Cell Transplantation
Year: 2025
Type: article
Study design: Observational Study
Abstract: Introduction: Epstein-Barr virus (EBV) reactivation is a common complication following allogeneic hematopoietic stem cell transplantation, with potential progression to PTLD. To prevent EBV-related diseases, the European Conference on Infections in Leukemia recommends regular post-transplant EBV-DNA-emia monitoring and early intervention with preemptive therapy, including rituximab (RTX) and reduction of immunosuppression. RTX is typically administered with 375mg/m² until EBV clearance, while no robust clinical trails confirmed the necessity of this high-dose regimen. Given that RTX may impair post-transplant immune reconstitution and increase infection risk, and considering that EBV-DNA emia primarily occurs within the first four months after allo-HSCT, with high EBV viral load being a risk factor for the development and increasing RTX administration frequency. We hereby report the efficacy and safety of fixed low-dose RTX (100 or 200 mg per dose) in high-risk patients with low-load EBV-DNA-emia who received ATG-containing conditioning regimens. Methods: Among 1755 consecutive patients who received ATG-containing regimens for allo-HSCT at the First Affiliated Hospital of Soochow University between January 2019 and March 2022, we included 77 patients who received fixed low-dose preemptive RTX for EBV-DNA-emia within four months post-transplant in this retrospective study. Patients with a high viral load (>10,000 copies/mL), probable PTLD or late-onset EBV reactivation were excluded. EBV-DNA was monitored with quantitative PCR in whole peripheral blood begins one week after stem cell infusion and was performed weekly for the first four months post-transplantation. EBV-DNA-emia is defined as detectable viremia exceeding 100 copies/mL in two consecutive measurements. Preemptive therapy with a fixed low dose of RTX (100 or 200 mg per dose). Treatment success was defined as achieving negative EBV-DNA results without subsequent development of PTLD. Results: Of 77 patients, 51 cases received 100mg of RTX, while 26 patients received 200mg. 66 patients received haplo-HSCT, 11 patients received URD-HSCT. The median time from transplantation to the first dose of RTX was 51 days (range, 18-113) and median EBV load at RTX initiation was 2260 copies/mL (range,212-9210). Of the 76 evaluable patients, 70 achieved viral clearance (92.1%, 95%CI, 85.9%-98.3%). The clearance rate was similar between the two cohort: 92% (84.2% to 99.8%) in the 100mg RTX cohort, 92.3% (81.3% to 100%) in the 200mg cohort. In the 100mg group, 28 patients tested negative after 1 dose, and 15 patients after 2 doses, while the corresponding numbers in the 200mg group were 8 and 12, respectively. Patients tolerated RTX treatment well, with no treatment discontinuations due to adverse events. Among the 77 patients, 43 underwent peripheral blood B-cell quantification by flow cytometry before and approximately two weeks after initiating RTX therapy. Of these, 41 achieved near-complete CD19+ B-cell depletion. Two (2.6%) patients developed PTLD. The median follow-up time was 44.2 (range,1.5 - 71.4) months. The 3-year OS, NRM and CIR were 70.7% (95%CI, 61.1% - 81.8%), 15.3% (95%CI, 6.0%- 23.6%), and 24.3% (95% CI, 13.5%- 33.8%). Three-year overall survival (100mg: 67.4%; 200mg: 76.9%, P=0.47), non-relapse mortality (100mg: 18.4%; 200mg: 8.9%, P=0.24), and cumulative relapse incidence (CIR) (100mg: 22.2%; 200mg: 28.2%, P=0.35) were statistically similar between two cohorts. In univariate and multivariate analyses, patients with an EBV load ≥2260 copies/ml demonstrated a tendency towards a poorer CIR (HR=0.43, 95%CI =0.16-1.15; P= 0.094). Clinically significant grade II-IV aGVHD occurred in 10 patients (13%) at day 100 after transplantation, with median onset of 44.5 (range 23-98) days. 5 patients developed EBV-viremia in the setting of grade II-IV aGVHD. Among 74 patients who survived for at least 100 days, chronic GVHD was diagnosed in 20 (27 %) patients, with the median onset of 5.8 (3.3-32.2) months. The cumulative incidence of chronic GVHD at third year was 29.1%. No statistically significant difference was observed in the incidence of cGVHD between the two dosage groups. (P=0.55). Conclusions: Low-dose RTX achieved a high EBV clearance rate (92%) with minimal toxicity, supporting its potential as an effective and safer alternative to the conventional high-dose regimen (375 mg/m²). prospective randomized multicentric trial with larger number of patient is needed.
Authors: Yi Wang, Yi Wang, Yaoyao Shen, Jiaqian Qi, Xiaohui Hu, Feng Chen, Yang Xu, Shengli Xue, Huiying Qiu, Xiaowen Tang, Yue Han, Suning Chen, Aining Sun, Yanming Zhang, Depei Wu, Ying Wang, Ying Wang
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: National Natural Science Foundation of China, Natural Science Foundation of Jiangsu Province, Soochow University, Priority Academic Program Development of Jiangsu Higher Education Institutions, Jiangsu Provincial Medical Center, Key Technologies Research and Development Program, National Key Research and Development Program of China
OpenAlex ID: W4417016367