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Updated: Jan 10, 2026
Generation of Multivirus-specific T Cells to Prevent/treat Viral Infections after Allogeneic Hematopoietic Stem Cell Transplant
Published on: May 27, 2011
Memory T Cell Donor Lymphocyte Infusion as a Treatment for Viral Infection After Pediatric Haploidentical
Yixian Li1, Yau Ki Wilson Chan1, Pui Wah Pamela Lee2
1Department of Paediatrics and Adolescent Medicine, Hong Kong Children's Hospital, Hong Kong SAR, China.
Background:
Viral reactivations, including cytomegalovirus (CMV), Epstein-Barr virus (EBV), adenovirus (ADV), human herpesvirus 6 (HHV-6), and BK virus (BKV), are significant infectious complications following haploidentical hematopoietic stem cell transplant (haplo-HCT). TCRαβ-depletion of haploidentical graft reduces the risk of graft-versus-host disease (GVHD) but may lead to delayed immune recovery and further increases the risk of viral reactivations. Prophylactic infusion of CD45RA-depleted donor memory T lymphocytes (TMDLI) has been reported as a strategy to accelerate recovery of T cell immunity after haplo-HCT.
Objectives:
To evaluate the safety and feasibility of therapeutic TMDLI for the treatment of viral infections before immune recovery within 100 days after TCRαβ-depleted haplo-HCT and prophylactic TMDLI administered on Day 0.
Study Design:
A retrospective review of patients who had received therapeutic TMDLI for one or more post-transplant viral infection(s) in a tertiary children's hospital from 2020 to 2023.
Results:
A total of 46 therapeutic TMDLIs were administered to 24 patients, with the first dose of infusion given between day 12 to 93 after haplo-HCT. CMV reactivation was the most common indication for TMDLI (n = 32, 69.6%), and the median time to achieve CMV clearance (defined as first negative viral polymerase chain reaction (PCR) test from the time of first therapeutic TMDLI) was 14 days. Other intended-to-treat viral infections or co-infections include ADV (n = 10), EBV (n = 6), BKV (n = 6) and HHV-6 (n = 3). The cumulative incidence of negative viral PCR for all viruses 30 days after the first TMDLI treatment was 75% (18/24 patients). All TMDLIs were well tolerated, with no de novo or recurrence of acute GVHD thereafter. One patient developed de novo moderate chronic GVHD after TMDLI treatment.
Conclusion:
TMDLI was a safe and feasible treatment for viral infections occurring within 100 days after pediatric TCRαβ-depleted haplo-HCT and prophylactic TMDLI.
Insights
Therapeutic TMDLI is a safe and feasible treatment for viral infections post-haploidentical hematopoietic stem cell transplant (haplo-HCT). This approach effectively clears viral reactivations like CMV, improving outcomes for pediatric patients.
Area of Science:
- Immunology
- Hematology
- Infectious Diseases
Background:
- Viral reactivations (CMV, EBV, ADV, HHV-6, BKV) are major complications after haploidentical hematopoietic stem cell transplant (haplo-HCT).
- TCRαβ-depletion reduces graft-versus-host disease (GVHD) but increases risks of delayed immune recovery and viral infections.
- CD45RA-depleted donor memory T lymphocytes (TMDLI) infusion is explored to accelerate T cell immunity post-haplo-HCT.
Purpose of the Study:
- To assess the safety and feasibility of therapeutic TMDLI for treating viral infections.
- To evaluate TMDLI in pediatric patients within 100 days post-TCRαβ-depleted haplo-HCT.
- To analyze TMDLI administered prophylactically on Day 0.
Main Methods:
- Retrospective review of pediatric patients receiving therapeutic TMDLI.
- Data collected from 2020 to 2023 at a tertiary children's hospital.
- Analysis of viral infections treated and patient outcomes.
Main Results:
- 24 patients received 46 therapeutic TMDLIs (Day 12-93 post-haplo-HCT).
- CMV reactivation was the primary indication (69.6%); median clearance time was 14 days.
- 75% of patients achieved viral clearance within 30 days; TMDLI was well-tolerated with no new acute GVHD.
Conclusions:
- Therapeutic TMDLI is a safe and feasible treatment option.
- It effectively addresses viral infections within 100 days post-pediatric TCRαβ-depleted haplo-HCT.
- TMDLI supports immune recovery and viral clearance in this vulnerable population.
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