Immunoglobiulin-specific Prophylaxis of Citomegalovirus Infections in Immunocompromised Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Human cytomegalovirus (CMV) is a globally prevalent, human-specific herpesvirus characterised by a lifelong latency after primary infection, an often asymptomatic reactivation and affecting up to 100% of adults based on region and age. CMV reactivation has serious risks for immunocompromised patients, especially those undergoing allogeneic hematopoietic stem cell transplantation (HSCT). In these patients, CMV can lead to graft failure, multiorgan disease, increased risk of other infections, GVHD, post-transplant lymphoproliferative disorders, and higher transplant-related mortality (TRM). Although antiviral prophylaxis, CMV infection occurs in 38-80% of HSCT recipients, but current antiviral drugs are insufficiently effective and they are associated with adverse effects. Furthermore, treatment failure is due to the high genetic variability of CMV. The protective role of virus-specific antibodies remains under debate. Some studies suggest that high neutralizing antibody titers protect transplant recipients from CMV, while others highlight the importance of T-cell responses. However, recent animal studies showed that humoral immunity alone can prevent CMV reactivation, even without T or NK cells. In solid-organ transplant patients, antibody titers ≥480 have been linked to reduced infection, shorter treatment, and full protection from CMV disease. Although the use of anti-CMV immunoglobulin remains controversial, the IRCCS Burlo Garofolo has used it as post-transplant prophylaxis and second-line treatment for over a decade. The main objective of their study was to assess whether CMV-specific immunoglobulin prophylaxis reduces CMV incidence and severity in pediatric HSCT patients. Secondary goals included evaluating its effect on transplant outcomes and its efficacy across different ethnic groups. A population pharmacokinetic (POP/PK) study was also conducted to better understand the drug's distribution and elimination and to identify factors influencing its pharmacokinetics in patients.

NCT Number	NCT07013370
Lead Sponsor	Antonello Di Paolo, M.D., Ph.D. Collaborators: IRCCS Burlo Garofolo
Conditions	Immunoglobulin Prophylaxis, Cytomegalovirus Infections, Allogeneic Hematopoietic Stem Cell Transplantation, Transplant-Related Disorder
Enrollment	150 participants
Start Date	2025-06-02
Primary Completion	2025-12-31 (estimated)
Study Completion	2026-06-02 (estimated)
Updated on ClinicalTrials.gov	2025-06-10