Memory T Cell Donor Lymphocyte Infusion as a Treatment for Viral Infection After Pediatric Haploidentical Hematopoietic Stem Cell Transplant.

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.