Figure 2
Figure 2. Monitoring of EBV-specific T cells in the circulation of patients with EBV-LPD treated with EBV-specific T cells or unstimulated DLIs. (A) Frequencies of EBV-specific T cells observed over a period of 12 weeks after initiation of T-cell therapy in the peripheral blood of patients who responded to treatment with EBV-specific T cells obtained from their stem cell donors (n = 8 patients evaluated). (B) Frequencies of EBV-specific T cells observed in peripheral blood of the patients with EBV-LPD who did not respond to treatment with EBV-specific T cells (n = 3) generated from PBMCs of their stem cell donors. (C) Monitoring of the EBV DNA levels (purple line) and EBV-CTLps (green line) of patient 15, who responded to treatment with EBV-specific T cells derived from the stem cell donor. EBV-CTLs were infused weekly for 3 consecutive weeks at doses of 1 × 106 cells/kg/infusion. After infusions of T cells, EBV-CTLps increased in frequency. Concurrently, EBV DNA levels in the peripheral blood of the patient decreased. (D) Monitoring of the EBV DNA levels (purple line) and EBV-CTLps (green line) of patient 41 who did not respond to treatment with EBV-specific T cells derived from the stem cell donor. EBV-CTLs were infused weekly for 3 consecutive weeks at doses of 1 × 106 cells/kg/infusion. No increase in EBV-CTLp frequency was observed over the period of 6 weeks of observation and the levels of EBV DNA remained high. (E) EBV-CTLps in patients who responded to therapy with DLIs from their HLA-matched stem cell donors (n = 3 patients evaluated). (F) EBV-CTLps in patients who did not respond to the therapy with DLIs (patients 43 and 45). (G-H) EBV DNA levels (purple line) and EBV-specific CTLps (green line) in the peripheral blood of patient 21, who responded to DLI treatment (G) and patient 45, who did not respond to the infusion of DLIs (H). (J) Monitoring of T-cell responses in the peripheral blood of patients with EBV-LPD who received EBV-specific T cells generated from third-party healthy donors (n = 5). The arrows indicate the times of the T-cell infusions for each of 3 patients treated and are presented in the same color as the line demonstrating the CTLps frequencies. Patients 1 and 6 achieved CR; patient 13 did not respond and died of PD.

Monitoring of EBV-specific T cells in the circulation of patients with EBV-LPD treated with EBV-specific T cells or unstimulated DLIs. (A) Frequencies of EBV-specific T cells observed over a period of 12 weeks after initiation of T-cell therapy in the peripheral blood of patients who responded to treatment with EBV-specific T cells obtained from their stem cell donors (n = 8 patients evaluated). (B) Frequencies of EBV-specific T cells observed in peripheral blood of the patients with EBV-LPD who did not respond to treatment with EBV-specific T cells (n = 3) generated from PBMCs of their stem cell donors. (C) Monitoring of the EBV DNA levels (purple line) and EBV-CTLps (green line) of patient 15, who responded to treatment with EBV-specific T cells derived from the stem cell donor. EBV-CTLs were infused weekly for 3 consecutive weeks at doses of 1 × 106 cells/kg/infusion. After infusions of T cells, EBV-CTLps increased in frequency. Concurrently, EBV DNA levels in the peripheral blood of the patient decreased. (D) Monitoring of the EBV DNA levels (purple line) and EBV-CTLps (green line) of patient 41 who did not respond to treatment with EBV-specific T cells derived from the stem cell donor. EBV-CTLs were infused weekly for 3 consecutive weeks at doses of 1 × 106 cells/kg/infusion. No increase in EBV-CTLp frequency was observed over the period of 6 weeks of observation and the levels of EBV DNA remained high. (E) EBV-CTLps in patients who responded to therapy with DLIs from their HLA-matched stem cell donors (n = 3 patients evaluated). (F) EBV-CTLps in patients who did not respond to the therapy with DLIs (patients 43 and 45). (G-H) EBV DNA levels (purple line) and EBV-specific CTLps (green line) in the peripheral blood of patient 21, who responded to DLI treatment (G) and patient 45, who did not respond to the infusion of DLIs (H). (J) Monitoring of T-cell responses in the peripheral blood of patients with EBV-LPD who received EBV-specific T cells generated from third-party healthy donors (n = 5). The arrows indicate the times of the T-cell infusions for each of 3 patients treated and are presented in the same color as the line demonstrating the CTLps frequencies. Patients 1 and 6 achieved CR; patient 13 did not respond and died of PD.

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