A clinical study of lyophilized intravenous human immunoglobulin containing high-titer cytomegalovirus-neutralizing antibody for the treatment of cytomegalovirus viremia after allogeneic hematopoietic stem cell transplantation

Abstract

Background: Cytomegalovirus (CMV) infection increases the risk of death after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, some patients do not respond to ganciclovir (GCV) or foscarnet sodium. Lyophilized intravenous human immunoglobulin containing high-titer CMV-neutralizing antibody (CMV-IVIG) is another option to further improve treatment safety and efficacy. This study was designed to evaluate the efficacy of the combination of CMV-IVIG with traditional antiviral drugs (GCV or foscarnet sodium) at different time points for the treatment of post-allo-HSCT CMV viremia and to determine the clinical value of CMV-IVIG as a preemptive treatment strategy. Methods: The clinical data of 73 patients who received allo-HSCT and concurrent CMV-IVIG to treat post-allo-HSCT CMV viremia at our hospital between January and September 2020 were retrospectively analyzed. The patients were divided into two groups based on the total dose of antithymocyte globulin (ATG) used in the pretransplant preconditioning regimen, i.e., the low-dose ATG group (rabbit ATG ≤6 mg/kg, porcine ATG ≤40 mg/kg) (n=19) and the high-dose ATG group (rabbit ATG >6 mg/kg, porcine ATG >40 mg/kg) (n=54). Real-time quantitative polymerase chain reaction (RQ-PCR) was performed to measure the peripheral CMV-DNA level. Patients with CMV viremia (CMV-DNA >1,000 copies/mL) received concurrent CMV-IVIG therapy [early (within 3 days after the diagnosis of CMV viremia) or late (after 3 days)]. The CMV-DNA conversion rate, the median time of CMV-DNA conversion, and the two-week response rate and reactivation rate were analyzed for different ATG doses and different time points of CMV-IVIG use. Results: The overall response rate to CMV-IVIG combined with traditional anti-CMV drugs was 100%. Early use of CMV-IVIG significantly reduced the median time of CMV-DNA conversion (14 vs. 21 days, P=0.000), especially in the high-dose ATG group (14 vs. 23 days, P=0.000). Conclusions: For patients with post-allo-HSCT CMV viremia, early use of CMV-IVIG effectively accelerates CMV-DNA conversion and peripheral CMV clearance, significantly improves the two-week response rate, and reduces the two-week reactivation rate. These effects are more pronounced in the high-dose ATG group.