Figure 3
Figure 3. Cumulative probability of response to ACT. (A) Cumulative probability of reduction or clearance of viremia after adoptive transfer of AdV-specific T cells with and without in vivo expansion of specific T cells. The two plots demonstrate the influence of in vivo expansion of AdV-specific T cells (defined as detected ≥0.01% IFN-γ+ T cells of viable T cells in blood samples of patients after ACT) for the cumulative probability of reduction (left) and clearance (right) of viremia until day 35 after adoptive T-cell therapy (n = 17). Patients 1, 4, 6, 7, 8, 10, 13, 23, 27, 32, 33, 34, and 35 are not represented in the figure because T-cell response could not be analyzed within the time period, patients already had negative viremia at time of ACT, or no quantitative analysis of the viral load was available. (B) AdV-related mortality in responders and nonresponders. Shown are the percentage of responders (defined as reduction >1 log change in copy numbers of viremia; n = 21) and nonresponders (defined as no reduction >1 log change in copy numbers or clearance of viremia; n = 8) who died as a result of AdV infection, as a result of other cause of death, or who survived within the observation period of 6 months after ACT. Numbers in the figure are rounded up so that 2 of 21 represents 10% instead of 9.52%. (C) Time to AdV-related mortality. Time of death within the follow-up of 6 months after ACT is demonstrated for the deceased responders (n = 6) and nonresponders (n = 8). (D) Correlation of the level of viremia with the velocity of viral clearance and virologic response after ACT. Time period until first viral clearance after ACT in correlation to the level of viremia at or prior to ACT is shown in the left graph. In evaluable patients with viral loads <10 000 copies per milliliter at time of ACT, first clearance of viremia could be achieved at a mean of 20 days (range, 6 to 67 days) after ACT. First viral clearance of evaluable patients with AdV loads >10 000 copies per milliliter was reached significantly later, at a mean of 57 days after ACT (range, 19 to 91 days). (Right) Time until first virologic response (defined as reduction of the viral load in copy numbers ≥1 log) in correlation to the level of viremia at or before ACT. In patients with viral loads <10 000 copies per milliliter at time of ACT, first virologic response could be achieved at a mean of 14 days (range, 6 to 22 days) after ACT. Significant reduction of the viral load in patients with AdV loads >10 000 copies per milliliter at ACT occurred for the first time at a mean of 26 days (range, 4 to 62 days) after ACT. For patients 24 and 25, viral load is indicated in copies per microgram of DNA and for patient 31, in genome equivalents per 20 000 cells. For patients 30, 31, and 35, time until first viral clearance or virologic response after first ACT is shown. (E) Correlation of the viral load at ACT with virologic response to ACT and with outcome of patients. The percentage of patients with viral loads <10 000 and >10 000 copies per milliliter at ACT within the groups of evaluable responders (n = 15), survivors (n = 10), and nonresponders (n = 5) in the time period of 6 months after ACT are shown. Patients 7, 8, 10, 13, 32, and 33 are not represented because viremia was negative at time of ACT; for patients 15, 22, and 34, only qualitative polymerase chain reaction results were available, and patient 1 is not included in the figure because the patient died shortly after ACT and could therefore not be classified as responder or nonresponder. For patients 24 and 25, viral load is indicated as 1000 copies per microgram of DNA, and for patient 31, in genome equivalents per 20 000 cells.

Cumulative probability of response to ACT. (A) Cumulative probability of reduction or clearance of viremia after adoptive transfer of AdV-specific T cells with and without in vivo expansion of specific T cells. The two plots demonstrate the influence of in vivo expansion of AdV-specific T cells (defined as detected ≥0.01% IFN-γ+ T cells of viable T cells in blood samples of patients after ACT) for the cumulative probability of reduction (left) and clearance (right) of viremia until day 35 after adoptive T-cell therapy (n = 17). Patients 1, 4, 6, 7, 8, 10, 13, 23, 27, 32, 33, 34, and 35 are not represented in the figure because T-cell response could not be analyzed within the time period, patients already had negative viremia at time of ACT, or no quantitative analysis of the viral load was available. (B) AdV-related mortality in responders and nonresponders. Shown are the percentage of responders (defined as reduction >1 log change in copy numbers of viremia; n = 21) and nonresponders (defined as no reduction >1 log change in copy numbers or clearance of viremia; n = 8) who died as a result of AdV infection, as a result of other cause of death, or who survived within the observation period of 6 months after ACT. Numbers in the figure are rounded up so that 2 of 21 represents 10% instead of 9.52%. (C) Time to AdV-related mortality. Time of death within the follow-up of 6 months after ACT is demonstrated for the deceased responders (n = 6) and nonresponders (n = 8). (D) Correlation of the level of viremia with the velocity of viral clearance and virologic response after ACT. Time period until first viral clearance after ACT in correlation to the level of viremia at or prior to ACT is shown in the left graph. In evaluable patients with viral loads <10 000 copies per milliliter at time of ACT, first clearance of viremia could be achieved at a mean of 20 days (range, 6 to 67 days) after ACT. First viral clearance of evaluable patients with AdV loads >10 000 copies per milliliter was reached significantly later, at a mean of 57 days after ACT (range, 19 to 91 days). (Right) Time until first virologic response (defined as reduction of the viral load in copy numbers ≥1 log) in correlation to the level of viremia at or before ACT. In patients with viral loads <10 000 copies per milliliter at time of ACT, first virologic response could be achieved at a mean of 14 days (range, 6 to 22 days) after ACT. Significant reduction of the viral load in patients with AdV loads >10 000 copies per milliliter at ACT occurred for the first time at a mean of 26 days (range, 4 to 62 days) after ACT. For patients 24 and 25, viral load is indicated in copies per microgram of DNA and for patient 31, in genome equivalents per 20 000 cells. For patients 30, 31, and 35, time until first viral clearance or virologic response after first ACT is shown. (E) Correlation of the viral load at ACT with virologic response to ACT and with outcome of patients. The percentage of patients with viral loads <10 000 and >10 000 copies per milliliter at ACT within the groups of evaluable responders (n = 15), survivors (n = 10), and nonresponders (n = 5) in the time period of 6 months after ACT are shown. Patients 7, 8, 10, 13, 32, and 33 are not represented because viremia was negative at time of ACT; for patients 15, 22, and 34, only qualitative polymerase chain reaction results were available, and patient 1 is not included in the figure because the patient died shortly after ACT and could therefore not be classified as responder or nonresponder. For patients 24 and 25, viral load is indicated as 1000 copies per microgram of DNA, and for patient 31, in genome equivalents per 20 000 cells.

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