eprintid: 1538549 rev_number: 152 eprint_status: archive userid: 608 dir: disk0/01/53/85/49 datestamp: 2017-01-31 12:41:29 lastmod: 2021-12-24 23:07:37 status_changed: 2017-10-03 14:02:51 type: article metadata_visibility: show creators_name: Rossig, C creators_name: Pule, M creators_name: Altvater, B creators_name: Saiagh, S creators_name: Wright, G creators_name: Ghorashian, S creators_name: Clifton-Hadley, L creators_name: Champion, K creators_name: Sattar, Z creators_name: Popova, B creators_name: Hackshaw, A creators_name: Smith, P creators_name: Roberts, T creators_name: Biagi, E creators_name: Dreno, B creators_name: Rousseau, R creators_name: Kailayangiri, S creators_name: Ahlmann, M creators_name: Hough, R creators_name: Kremens, B creators_name: Sauer, MG creators_name: Veys, P creators_name: Goulden, N creators_name: Cummins, M creators_name: Amrolia, PJ title: Vaccination to improve the persistence of CD19CAR gene-modified T cells in relapsed pediatric acute lymphoblastic leukemia ispublished: pub divisions: UCL divisions: B02 divisions: C10 divisions: D19 divisions: H01 divisions: G98 divisions: D13 divisions: G24 note: © 2017 Macmillan Publishers Limited. All rights reserved. abstract: Trials with 2nd generation CD19 chimeric antigen receptors (CAR) T-cells report unprecedented responses but associated with risk of Cytokine Release Syndrome (CRS). Instead, we studied use of donor Epstein Barr virus-specific T-cells (EBV CTL) transduced with a 1st generation CD19CAR, relying on the endogenous T-cell receptor for proliferation. We conducted a multi- center phase I/II study of donor CD19CAR transduced EBV CTL in pediatric ALL. Patients were eligible pre-emptively if they developed molecular relapse (>5 × 10-4) post-1st SCT, or prophylactically post-2nd SCT. An initial cohort showed poor expansion/persistence. We next investigated EBV-directed vaccination to enhance expansion/persistence. 11 patients were treated. No CRS, neurotoxicity or GVHD was observed. At 1 month, 5 patients were in CR (4 continuing, 1 de-novo), 1 PR, 3 had stable disease and 3 no response. At a median follow-up of 12 months, 10 of 11 have relapsed, 2 are alive with disease and 1 alive in CR 3 years. Whilst CD19CAR CTL expansion was poor, persistence was enhanced by vaccination. Median persistence was 0 (range 0-28) days without vaccination compared to 56 (range 0-221) days with vaccination (P=0.06). This study demonstrates feasibility of such multi-center studies and the potential for enhancing persistence with vaccination.Leukemia accepted article preview online, 27 January 2017. doi:10.1038/leu.2017.39. date: 2017-03-10 date_type: published official_url: http://dx.doi.org/10.1038/leu.2017.39 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green article_type_text: Journal Article verified: verified_manual elements_id: 1205497 doi: 10.1038/leu.2017.39 pii: leu201739 lyricists_name: Amrolia, Persis lyricists_name: Champion, Kim lyricists_name: Clifton-Hadley, Laura lyricists_name: Ghorashian, Sara lyricists_name: Hackshaw, Allan lyricists_name: Hough, Rachel lyricists_name: Popova, Bilyana lyricists_name: Pule, Martin lyricists_name: Veys, Paul lyricists_id: PJAMR87 lyricists_id: KCHAM39 lyricists_id: LCLIF97 lyricists_id: SGHOR34 lyricists_id: AHACK11 lyricists_id: REHOU43 lyricists_id: BPOPO76 lyricists_id: MPULE38 lyricists_id: PAVEY50 actors_name: Ghorashian, Sara actors_id: SGHOR34 actors_role: owner full_text_status: public publication: Leukemia volume: 31 pagerange: 1087-1095 event_location: England issn: 1476-5551 citation: Rossig, C; Pule, M; Altvater, B; Saiagh, S; Wright, G; Ghorashian, S; Clifton-Hadley, L; ... Amrolia, PJ; + view all <#> Rossig, C; Pule, M; Altvater, B; Saiagh, S; Wright, G; Ghorashian, S; Clifton-Hadley, L; Champion, K; Sattar, Z; Popova, B; Hackshaw, A; Smith, P; Roberts, T; Biagi, E; Dreno, B; Rousseau, R; Kailayangiri, S; Ahlmann, M; Hough, R; Kremens, B; Sauer, MG; Veys, P; Goulden, N; Cummins, M; Amrolia, PJ; - view fewer <#> (2017) Vaccination to improve the persistence of CD19CAR gene-modified T cells in relapsed pediatric acute lymphoblastic leukemia. Leukemia , 31 pp. 1087-1095. 10.1038/leu.2017.39 <https://doi.org/10.1038/leu.2017.39>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/1538549/1/Ghorashian_CD19TPALLmanuscript_leukaemia_resubmission_clean.pdf document_url: https://discovery.ucl.ac.uk/id/eprint/1538549/2/Ghorashian_CD19TPALL%20table%201_resubmission_clean.pdf document_url: https://discovery.ucl.ac.uk/id/eprint/1538549/3/Ghorashian_CD19TPALL%20figure_1_resub.pdf document_url: https://discovery.ucl.ac.uk/id/eprint/1538549/4/Ghorashian_CD19TPALL%20figure_2_resub.pdf document_url: https://discovery.ucl.ac.uk/id/eprint/1538549/5/Ghorashian_CD19TPALL%20figure_3_resub.pdf document_url: https://discovery.ucl.ac.uk/id/eprint/1538549/6/Ghorashian_CD19TPALL%20figure_4_resub.pdf document_url: https://discovery.ucl.ac.uk/id/eprint/1538549/7/Ghorashian_CD19TPALL%20figure_5_resub.pdf document_url: https://discovery.ucl.ac.uk/id/eprint/1538549/8/Ghorashian_CD19TPALL_Table%202_resubmission.pdf document_url: https://discovery.ucl.ac.uk/id/eprint/1538549/9/Ghorashian_Supplementary%20methods%20CD19TPALL_for%20resubm.pdf document_url: https://discovery.ucl.ac.uk/id/eprint/1538549/10/Ghorashian_CD19TPALL%20supp%20table%201%20eligibility%20SG180416.pdf document_url: https://discovery.ucl.ac.uk/id/eprint/1538549/11/Ghorashian_Supplementary%20Fig1.pdf document_url: https://discovery.ucl.ac.uk/id/eprint/1538549/12/Ghorashian_Supplementary%20Fig2.pdf document_url: https://discovery.ucl.ac.uk/id/eprint/1538549/13/Ghorashian_Supplementary%20Fig3.pdf document_url: https://discovery.ucl.ac.uk/id/eprint/1538549/14/Ghorashian_Supplementary%20Fig4.pdf document_url: https://discovery.ucl.ac.uk/id/eprint/1538549/15/Ghorashian_Supplementary%20Fig5.pdf