Evaluation of the Efficacy of a Cytomegalovirus-Specific Immune Reconstitution-Incorporated Scoring System in Guiding the Duration of Antiviral Prophylaxis to Reduce Cytomegalovirus Infection Following Letermovir Discontinuation
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 1,114
- 主要终点
- incidence of CMV reactivation and cs CMV infection
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •(1) Recipients who meet either of the following conditions:
- •CMV IgG-positive recipients undergoing HLA-haploidentical hematopoietic stem cell transplantation (HSCT).
- •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.
排除标准
- •(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.
研究组 & 干预措施
CMV high risk patients after transplantation
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.
结局指标
主要结局
incidence of CMV reactivation and cs CMV infection
时间窗: one year after letermovir discontinuation
次要结局
- Incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)(one year)
- All-cause mortality(one year)
- treatment-related mortality(one year)