Management of cytomegalovirus reactivation in high-risk haematopoietic stem cell transplant recipients by using cytomegalovirus-specific immunoglobulins

Background: Cytomegalovirus (CMV) infection/reactivation continues to represent one of the most opportunistic infections after haematopoietic stem cell transplantation (HSCT). CMV infection can escalate to CMV disease with complex outcomes that may be challenging to manage. CMV can indirectly contribute to reduced overall survival (OS) and increase non–relapse mortality (NRM) in HSCT patients. Prevention of CMV and early pre–emptive strategies are fundamental to reduce the risk of end–organ disease. Risk factors for CMV infection or disease include CMV seropositive recipients, mismatched and unrelated transplants, the use of T cell depletion agents, steroid therapy, graft–versus–host disease (GvHD), administration of CMV–positive blood products in seronegative recipients, among other factors. Ganciclovir or valganciclovir remain the mainstream of CMV management in HSCT. Due to adverse effects such as leukopenia and nephrotoxicity, some patients may exhibit intolerance or necessitate early discontinuation of such drugs. A recent review indicated that the pre–emptive use of CMVIG resulted in an overall response in 65%–100% of patients with a clearance time of 14 to 21 days (Whittaker et al 2023). Methods: Objectives: To assess the efficacy of CMVIG in the early pre–emptive management of CMV in high–risk HSCT recipients. Methods: Between December 2022 and October 2024, 13 high–risk patients’ post–prophylaxis with early detection of CMV reactivation were treated with CMVIG. All patients were managed with CMVIG as monotherapy. Clinical parameters such as viral load (IU/ml), medication side effects, and patient tolerance were systemically evaluated. Results: All patients experiencing CMV reactivation exhibited at least one–risk factor predisposing them to CMV reactivation, including D + /R+ serostatus, exposure to anti–thymocyte globulin (ATG), or received a matched unrelated donor (MUD) or haploidentical donor. All patients were receiving Valacyclovir 500 mg b.i.d. for prophylaxis. The median age at transplantation was 53.8 years (range: 24–69). The median viremia level detected during treatment was 3175 IU/ml. (1300 IU/ml. min; 7000 IU/ml. max) with no clinical symptoms. A favourable response defined as achieving undetectable CMV viral load was achieved in all patients. None of the patients required additional antiviral therapy following early initiation of CMVIG. The median duration to achieve viral response was 20 days with CMV load monitoring 2 times per week. CMVIG was well tolerated among all patients, with no reported adverse reactions recorded. Conclusions: This single–centre experience demonstrates the clinical efficacy of CMVIG as monotherapy in the early pre–emptive management of CMV infection, achieving complete remission of in all patients with no product related side effects recorded. CMVIG may be considered as a suitable option in the pre–emptive management to enhance virus clearance, and to avoid or shorten the need for antiviral therapy in high–risk patients or in patients presenting with intolerance to antiviral drugs