EBV-associated T/NK-cell Lymphoproliferative Diseases, Letermovir, Refractory/Relapsed EBV-related Hemophagocytic Lymphohistiocytosis
Conditions
Keywords
EBV, Letermovir, EBV-associated T/NK-cell lymphoproliferative diseases, refractory/relapsed EBV-related hemophagocytic lymphohistiocytosis
Brief summary
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.
Interventions
DRUGLetermovir
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 initiated only when plasma PCR exceeds threshold.
Sponsors
Beijing Children's Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 18 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Clinically Significant CMV Infection (cs-CMVi) and EBV Infection (cs-EBVi) | Up to 180 days and 360 days post-transplant | To evaluate the incidence of clinically significant CMV and EBV infections in pediatric patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) with or without letermovir prophylaxis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Other Viral Infections and Transplant-Related Complications | Up to 100, 180, 270, and 360 days post-transplant | To assess the incidence of other viral infections (e.g., BKV, HHV-6/7, RSV, ADV, HSV), graft-versus-host disease (GvHD), post-transplant lymphoproliferative disorder (PTLD), thrombotic microangiopathy (TMA), graft failure, relapse, overall survival (OS), and immune reconstitution (T/B/NK cell counts and function). |
Countries
China
Contacts
CONTACTJun Yang, Doctor
Outcome results
None listed