A Randomized Controlled Trial of Prophylactic Rituximab to Reduce Clinically Significant EBV DNAemia After Allogeneic Hematopoietic Stem Cell Transplantation

A Prospective, Randomized, Controlled, Open-Label Clinical Trial With Blinded Endpoint Assessment of Prophylactic Rituximab for Reducing Clinically Significant EBV Viremia After Allogeneic Hematopoietic Stem Cell Transplantation

This is a single-center, prospective, randomized, open-label clinical trial with blinded endpoint assessment for patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aim to explore whether low-dose preventive rituximab can lower the risk of clinically significant Epstein-Barr virus (EBV) viremia within 180 days after transplantation.

Patients aged 16-65 years who receive allo-HSCT and carry medium-to-high risks of EBV reactivation will be enrolled. All eligible participants will be randomly split into two groups at day +21 after transplant at a 1:1 ratio.

Intervention group: Standard post-transplant supportive care plus two low doses of rituximab (100mg intravenous infusion on day +21 and day +28).

Control group: Only standard routine post-transplant management without preventive rituximab.

All participants will receive regular scheduled blood tests and outpatient follow-up visits up to 1 year after transplantation. We will monitor EBV viral load, cytomegalovirus (CMV) infection, graft-versus-host disease (GVHD), infection complications, immune function recovery, as well as long-term survival. We will also record all adverse reactions related to rituximab infusion, low immunoglobulin levels and other safety events.

The main study outcome is the cumulative rate of clinically significant EBV viremia within 180 days post transplant. All endpoint judgments will be completed by independent researchers to reduce assessment bias. This trial hopes to confirm the safety and clinical value of low-dose rituximab prevention, and provide reliable clinical evidence for EBV infection prevention after hematopoietic stem cell transplantation.

Inclusion Criteria:

- Aged between 16 and 65 years old. Recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Clinically stable condition allowing administration of study intervention at post-transplant Day +21.

EBV-DNA quantitative test completed within 48 hours prior to randomization. Written informed consent signed by the participant or legal authorized representative.

Exclusion Criteria:

- Presence of clinically significant EBV infection or meeting criteria for EBV preemptive therapy before randomization.

Prior rituximab administration during conditioning regimen. Confirmed or highly suspected post-transplant lymphoproliferative disorder (PTLD).

Severe anaphylactic history to rituximab or any excipients of the preparation. Active uncontrolled severe systemic infection. Active hepatitis B virus (HBV) infection without standardized antiviral prophylaxis or treatment.

Pregnant or breastfeeding female subjects. Subjects judged ineligible for participation by the investigator for any other reason.