Multicenter study of banked third-party virus-specific T cells to treat severe viral infections after hematopoietic stem cell transplantation by Ann M.

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Presentation transcript:

Multicenter study of banked third-party virus-specific T cells to treat severe viral infections after hematopoietic stem cell transplantation by Ann M. Leen, Catherine M. Bollard, Adam M. Mendizabal, Elizabeth J. Shpall, Paul Szabolcs, Joseph H. Antin, Neena Kapoor, Sung-Yun Pai, Scott D. Rowley, Partow Kebriaei, Bimalangshu R. Dey, Bambi J. Grilley, Adrian P. Gee, Malcolm K. Brenner, Cliona M. Rooney, and Helen E. Heslop Blood Volume 121(26):5113-5123 June 27, 2013 ©2013 by American Society of Hematology

Cumulative response rates at 6 weeks postinfusion of VSTs Cumulative response rates at 6 weeks postinfusion of VSTs. (A) Results based on the first CR/PR in all 50 patients, regardless of the type of infection. Cumulative response rates at 6 weeks postinfusion of VSTs. (A) Results based on the first CR/PR in all 50 patients, regardless of the type of infection. (B) Results by specific viral infection: CMV, AdV, and EBV. The curves were constructed with use of the cumulative incidence function. Further details are given in “Statistical analysis.” Ann M. Leen et al. Blood 2013;121:5113-5123 ©2013 by American Society of Hematology

Outcomes after treatment with banked VSTs: CMV-infected patients. Outcomes after treatment with banked VSTs: CMV-infected patients. (A) Depiction of viral load measurements before and during 6 weeks postinfusion of VSTs in 19 evaluable patients (responders and nonresponders) treated for persistent CMV infection. Results are presented as copies per milliliter (CMV detected in blood) or as copies per cell in patients with CMV antigenemia. Because viral loads were measured by different assays at different institutions, interpatient comparisons should not be made. (B) An example of a patient with CMV colitis with evidence of viral inclusions on H&E staining that contained CMV by immunostaining (left panel). After VST infusion, there was a complete resolution of CMV colitis and no evidence of viral inclusions by H&E staining (right panel). (C) Frequency of CMVpp65–directed T cells in peripheral blood before and at weeks 1, 2, 4, and 12 postinfusion, as measured with an IFN-γ ELIspot assay after overnight stimulation of PBMCs with CMVpp65 pepmix. Results are expressed as mean (±SD) spot-forming cells (SFCs) per 2 × 105 input cells. Ann M. Leen et al. Blood 2013;121:5113-5123 ©2013 by American Society of Hematology

Outcomes after treatment with banked VSTs: AdV-infected patients. Outcomes after treatment with banked VSTs: AdV-infected patients. (A) Serial viral load measurements before and during 6 weeks post-VST infusion in 17 evaluable patients (responders and nonresponders) treated for persistent AdV. Results are presented as copies per milliliter, where Adv was detected either in blood or in the stool. Because viral loads were measured by different assays at different institutions, interpatient comparisons should not be made. In (B) and (C), elevated AdV loads are detected in both blood (B) and stool (C) in a patient (#59) whose infection resolved after VST infusion. Results are expressed as copies per milliliter. (D) Frequency of AdV-directed T cells in peripheral blood before and at weeks 1, 2, 4, and 6 postinfusion, as measured with an IFN-γ ELIspot assay after overnight stimulation of PBMCs with Adv pepmixes (Hexon and Penton). Results are expressed as mean (±SD) SFCs per 2 × 105 input cells. Ann M. Leen et al. Blood 2013;121:5113-5123 ©2013 by American Society of Hematology

Outcomes after treatment with banked VSTs: EBV-infected patients. Outcomes after treatment with banked VSTs: EBV-infected patients. (A) Serial viral load measurements before and during 6 weeks post-VST infusion in patients (responders and nonresponders) with EBV-LPD. Results are presented as copies per milliliter. (B, left) Positron emission tomography scan of a patient with extensive and progressive LPD despite sirolimus therapy, with a second scan (right) showing complete resolution of all lesions after VST infusion. (C) Frequency of EBV-directed T cells in peripheral blood before and at weeks 1, 2, and 4 postinfusion, as measured with an IFN-γ ELIspot assay after overnight stimulation of PBMCs with EBV lymphoblastoid cell lines. Results are expressed as mean (±SD) SFC per 2 × 105 input cells. Ann M. Leen et al. Blood 2013;121:5113-5123 ©2013 by American Society of Hematology