Letermovir Prophylaxis in Children With EBV-Positive T/NK-Cell Lymphoproliferative Disease and Refractory/Relapsed EBV-Associated Hemophagocytic Lymphohistiocytosis

Официальное название

Impact of Letermovir Prophylaxis on Viral Infections After Allogeneic Hematopoietic Stem Cell Transplantation in Children With EBV-Positive T/NK-Cell Lymphoproliferative Disease and Refractory/Relapsed EBV-Associated Hemophagocytic Lymphohistiocytosis

Обзор

This study investigates the impact of letermovir prophylaxis on viral infections (including CMV, EBV, BKV, HHV-6/7, RSV, ADV, HSV, etc.) following allogeneic hematopoietic stem cell transplantation in pediatric patients with EBV-associated T/NK-cell lymphoproliferative diseases and refractory/relapsed EBV-related hemophagocytic lymphohistiocytosis. Additionally, we examine its effects on other transplantation complications, including engraftment failure, graft-versus-host disease (GvHD), disease relapse, thrombotic microangiopathy (TMA), overall survival (OS), post-transplant lymphoproliferative disorder (PTLD) incidence, and immune reconstitution.

Вмешательства

• Препарат Letermovir
  Arm 1 (Letermovir Prophylaxis): Pediatric patients receive oral letermovir once daily from day 0 to day 100 post-transplant. Prophylaxis may be extended to day 200 if high-risk factors persist (steroid use, poor immune reconstitution). Dosing: 480mg (≥30kg), 240mg (15-30kg), 120mg (7.5-15kg), 80mg (6-7.5kg); halved if co-administered with cyclosporine. Arm 2 (Control): Historical control cohort (2018-2023) receiving no routine CMV prophylaxis; preemptive therapy with ganciclovir/foscarnet initi

Первичные конечные точки

• Incidence of Clinically Significant CMV Infection (cs-CMVi) and EBV Infection (cs-EBVi) [Срок оценки: Up to 180 days and 360 days post-transplant]

Вторичные конечные точки (1)

• Incidence of Other Viral Infections and Transplant-Related Complications [Срок оценки: Up to 100, 180, 270, and 360 days post-transplant]

Критерии участия

Критерии включения

• Diagnosed with EBV-positive T/NK lymphoproliferative disease (EBV-T/NK LPD) according to ICC 2022 criteria, or diagnosed with refractory/relapsed EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) according to the 2004-HLH diagnostic criteria;
• Undergoing first allogeneic hematopoietic stem cell transplantation (allo-HSCT) at the study center;
• Age < 18 years;
• CMV seropositive (IgG+) prior to transplantation;
• Presence of at least one high-risk factor for CMV infection: haploidentical transplantation, HLA-mismatched transplantation, receipt of ATG (including ATLG/ALG) in conditioning, sustained corticosteroid use post-conditioning, donor/recipient CMV serostatus mismatch, or positive NGS result pre-transplant.

Критерии исключения

• History of CMV end-organ disease within 6 months prior to enrollment;
• Severe hepatic dysfunction (defined as Child-Pugh Class C);
• End-stage renal impairment with creatinine clearance < 10 mL/min (calculated by Cockcroft-Gault equation);
• Prior allogeneic hematopoietic stem cell transplantation;
• Expected survival ≤ 3 months;
• Received radiation therapy during conditioning;
• Initiation of letermovir prophylaxis after day 28 post-transplant;
• Letermovir dosage or administration not in accordance with the prescribing information;
• Lack of signed informed consent.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Профилактика

Центры проведения

Китай · 1 центр

• Beijing Children's Hospital, Capital Medical University — Пекин

Идентификаторы

NCT: NCT07488728 · [2025]-Y-242-D

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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