With the increasing use of letermovir and considering that haploidentical hematopoietic stem cell transplantation (haplo-HSCT) predominates in China alongside a high CMV seroprevalence in the population, multiple domestic centers have reported cases of CMV infection after letermovir discontinuation. Currently, there is no clear definition for the high-risk population who may benefit from extended letermovir prophylaxis. This study aims to utilize CMV-specific immune reconstitution to identify high-risk individuals for CMV infection after letermovir cessation post-transplant, thereby guiding the timing of letermovir discontinuation and balancing the risks and safety associated with prolonged prophylaxis.

Based on the established scoring system for cytomegalovirus-specific immune reconstitution, guide the discontinuation of letermovir after transplantation to reduce the incidence of CMV infection within one year after letermovir discontinuation.

Inclusion Criteria:

• (1) Recipients who meet either of the following conditions:

  1. CMV IgG-positive recipients undergoing HLA-haploidentical hematopoietic stem cell transplantation (HSCT).
  2. CMV IgG-negative recipients receiving a graft from a CMV IgG-positive donor, and who have received letermovir as CMV prophylaxis post-transplant without prior discontinuation.

• (2) Plasma CMV-DNA level below the lower limit of detection (local threshold: 400 copies/mL) within 5 days before enrollment.

• (3) Age ≥ 18 years.

• (4) Ability to provide written informed consent independently.

• (5) Negative for HIV, HBV, and HCV.

• (6) Written informed consent must be provided before initiation of any study procedure. Consent may be provided by the patient or a legally authorized representative if, in the investigator's judgment, obtaining consent directly from the patient is not in the patient's best medical interest.

Exclusion Criteria:

• (1) Prior clinical diagnosis of CMV infection, CMV disease, or CMV viremia before enrollment;
• (2) Received ganciclovir, valganciclovir, foscarnet, acyclovir (oral dose >3200 mg daily, or intravenous dose >25 mg/kg daily), valacyclovir (oral dose >3000 mg daily), or famciclovir (oral dose >1500 mg daily) within 7 days before enrollment;
• (3) Received the following treatments within 30 days before enrollment: cidofovir, CMV hyperimmune globulin, any experimental anti-CMV therapy or biologics;
• (4) Presence of uncontrolled infection, requirement for mechanical ventilation, or hemodynamic instability at enrollment;
• (5) Suffering from mental illness or other conditions that prevent compliance with study treatment and monitoring requirements;
• (6) Inability or unwillingness to sign the informed consent form;
• (7) Other special circumstances deemed ineligible by the investigator.

For enrolled subjects, at 3 months after transplantation, apply a predictive model incorporating CMV-specific immune reconstitution to evaluate the risk of CMV infection after discontinuation of letermovir. Based on the prediction results, define low-risk, intermediate-risk, and high-risk categories. For low-risk patients, direct discontinuation of letermovir is recommended; for intermediate-risk patients, discontinuation may be considered, but close monitoring of peripheral blood CMV-DNA is required after discontinuation; for high-risk patients, extending letermovir treatment until 200 days after transplantation is recommended.