T‐cell depletion (TCD) effectively reduces severe graft‐versus‐host disease in recipients of HLA‐mismatched allografts. However, TCD is associated with delayed immune recovery and increased infections. We hypothesized that specific depletion of CD45RA+ naive T cells, rather than broad depletion of CD3+ T cells, can preserve memory‐immunity in the allografts and confer protection against important viral infections in the early post‐transplant period.

Sixty‐seven patients who received TCD haploidentical donor transplantation for hematologic malignancy on 3 consecutive trials were analyzed.

Patients receiving CD45RA‐depleted donor grafts had 2000‐fold more donor T cells infused, significantly higher T‐cell counts at Day +30 post transplant (550/μL vs 10/μL; P < .001), and higher T‐cell diversity by Vbeta spectratyping at Day +100 (P < .001). Importantly, these recipients experienced a significant reduction in both the incidence (P = .002) and duration (P = .02) of any viremia (cytomegalovirus, Epstein‐Barr virus, or adenovirus) in the first 6 months post transplant. Specifically, recipients of CD3‐depleted grafts were more likely to experience adenovirus viremia (27% vs 4%, P = .02).

CD45RA‐depletion provided a large number of donor memory T cells to the recipients and was associated with enhanced early T‐cell recovery and protection against viremia.