Impaired recovery of Epstein-Barr virus (EBV)-specific CD8+ T lymphocytes after partially T-depleted allogeneic stem cell transplantation may identify patients at very high risk for progressive EBV reactivation and lymphoproliferative disease

Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes are considered pivotal to prevent lymphoproliferative disease (LPD) in allogeneic stem cell transplantation (SCT) recipients. We evaluated the recovery of EBV-specific CD8(+) T cells after partially T-cell-depleted SCT and studied the interaction between EBV-specific CD8(+) T cells, EBV reactivation, and EBV-LPD. EBV-specific CD8(+) T cells were enumerated using 12 class, I HLA tetramers presenting peptides derived from 7 EBV proteins. Blood samples were taken at regular intervals after SCT in 61 patients, and EBV DNA,levels Were assessed by real-time polymerase chain reaction. Forty-five patients showed EBV reactivation, including 25 With high-level reactivation (le, more than 1000 genome equivalents [geq] per milliliter). Nine of these 25 patients progressed to EBV-LPD. CD8(+) cells specific for latent or lytic EBV epitopes repopulated the peripheral blood at largely similar rates. In most patients, EBV-specific CD8(+) T-cell counts had returned to normal levels within 6 months after SCT. Concurrently, the incidence of EBV reactivations, clearly decreased. Patients with insufficient EBV-specific CD8(+) T-cell recovery were at high risk for EBV reactivation in the first 6 months after SCT. Failure to detect EBV-specific CD8(+) T cells in patients with high-level reactivation was associated With the subsequent development of EBV-LPD (P = .048). Consequently, the earlier defined positive predictive value of approximately 40%, based on high-level EBV reactivation. only, increased to 100% in patients without detectable EBV-specific CD8(+) T cells. Thus, impaired recovery of EBV-specific CD8(+) T cells in patients with high-level EBV reactivation may identity a subgroup at very high risk for EBV-LPD and supports that EBV-specific CD8(+) T cells protect SCT recipients from progressive, EBV. reactivation and EBV-LPD. (C) 2003 by The American Society of Hematology.