After allogeneic hematopoietic stem cell transplantation (allo-HSCT), recipients are immunocompromised and at increased risk of complications, including cytomegalovirus (CMV) infection. International clinical guidelines for the management of CMV infection post-allo-HSCT recommend three main strategies: minimizing infection risk, prevention, and preemptive therapy. However, traditional antiviral agents have not been approved for CMV prophylaxis in allo-HSCT recipients and are associated with significant adverse effects and the development of resistance, leaving the CMV prevention needs of this patient population unmet. Recent studies have demonstrated that letermovir prevents potent and highly specific antiviral activity against CMV, and it has been approved for CMV prophylaxis within the first 100 days post-allo-HSCT. Furthermore, evidence suggests that extending letermovir administration up to 28 weeks further reduces the risk of CMV infection in the later post-transplant period without increasing drug-related mortality. In China, the post-allo-HSCT CMV prevention strategy faces challenges such as limited treatment options, unclear guideline recommendations, non-standardized drug usage in certain medical institutions, and insufficient monitoring. This study aims to provide robust, evidence-based support for the use of letermovir in high-risk CMV reactivation among adult allo-HSCT recipients, thereby broadening clinical treatment choices.
The patients have decided to undergo an initial allogeneic hematopoietic stem cell transplantation (allo-HSCT).
The patients are ≥18 years old.
The patients are CMV seropositive prior to transplantation.
Patients who have previously received allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Patients with evidence of CMV viremia at any time prior to enrollment.
Patients with a history of CMV end-organ disease within 6 months prior to enrollment.
Patients with suspected or known allergy to letermovir or any active or inactive components of similar drugs.
Parallel
Letermovir (0-24w）
DrugPatients will begin receiving prophylactic treatment with domestically produced letermovir from day 0 to day 28 post-allo-HSCT, at a dose of 480 mg, administered orally once daily. If used in combination with cyclosporine, the dose should be reduced to 240 mg once daily. The treatment will continue until 24 weeks post-transplant (approximately 170 days).
Letermovir (0-14w）
DrugPatients will begin receiving prophylactic treatment with domestically produced letermovir from day 0 to day 28 post-allo-HSCT, at a dose of 480 mg, administered orally once daily. If used in combination with cyclosporine, the dose should be reduced to 240 mg once daily. The treatment will continue until 14 weeks post-transplant (approximately 100 days).
The incidence of clinically significant CMV infection (csCMVi) within 24 weeks post-transplant
csCMVi: the occurrence of CMV disease or CMV viremia requiring preemptive therapy
Incidence of resistant or refractory CMV infection within 24 weeks post-transplant
Refractory CMV viremia: CMV viral load remains unchanged or increases after 2 weeks of appropriate anti-CMV treatment. Refractory CMV disease: Symptoms or signs of CMV disease show no improvement or continue to progress after 2 weeks of appropriate anti-CMV treatment.
Time to initiation of preemptive therapy and duration of treatment for CMV infection within 24 weeks post-transplant
Preemptive Therapy for CMV: A treatment strategy where antiviral medications are administered early, based on the detection of CMV reactivation (e.g., through viral load monitoring) before symptoms or disease develop, to prevent the progression to CMV disease.
Incidence and severity of acute graft-versus-host disease (GVHD) within 100 days post-transplant
Acute GVHD: A complication that occurs shortly after allogeneic stem cell transplantation, where the donor's immune cells attack the recipient's tissues, typically affecting the skin, liver, and gastrointestinal tract. It usually develops within the first 100 days post-transplant and can range from mild to severe.
Incidence and severity of chronic GVHD within 24 weeks post-transplant
Chronic GVHD: A long-term complication following allogeneic stem cell transplantation, where the donor's immune cells attack the recipient's healthy tissues, affecting organs such as the skin, liver, lungs, and eyes. It can range from mild to severe and may require prolonged immunosuppressive therapy.
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