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Supplementary Methods, Tables S1-4, Figures S1-4 from Infusion of Alloanergized Donor Lymphocytes after CD34-selected Haploidentical Myeloablative Hematopoietic Stem Cell Transplantation

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posted on 2023-03-31, 20:49 authored by Jeff K. Davies, Lisa L. Brennan, John R. Wingard, Christopher R. Cogle, Neena Kapoor, Ami J. Shah, Bimalangshu R. Dey, Thomas R. Spitzer, Marcos de Lima, Laurence J. Cooper, Peter F. Thall, Richard E. Champlin, Lee M. Nadler, Eva C. Guinan

Table S1 Patients, donors, HLA-mismatches and conditioning; Table S2 Cell doses in stem cell transplant, engraftment and chimerism; Table S3 ADLI dose and timing and allostimulator source; Table S4 Patient outcomes; Figure S1 Schema for clinical study; Figure S2 Alloanergization efficiency of DLI by centre and by dose level; Figure S3 Residual alloreactivity in aDLI and occurrence of acute GvHD after T-cell depleted haploidentical HSCT and aDLI; Figure S4 Phenotype of CD4+ regulatory T-cell (Treg) in patient peripheral blood after T-cell depleted haploidentical HSCT and aDLI

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NIH

Leukemia and Lymphoma Society

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CRUK

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ARTICLE ABSTRACT

Purpose: Allogeneic hematopoietic stem-cell transplantation (HSCT) is a curative treatment for many hematologic cancers. Use of haploidentical (mismatched) donors increases HSCT availability but is limited by severe graft-versus-host disease (GvHD) and delayed immune reconstitution. Alloanergization of donor T cells is a simple approach to rebuild immunity while limiting GvHD after haploidentical HSCT, but the optimal T-cell dose and impact on immune reconstitution remain unknown.Patients and Methods: We performed a multicenter phase I trial of alloanergized donor lymphocyte infusion (aDLI) after CD34-selected myeloablative haploidentical HSCT. The primary aim was feasibility and safety with secondary aims of assessing the less frequently addressed issue of impact on immune reconstitution.Results: Nineteen patients with high-risk acute leukemia or myelodysplasia were enrolled. Engraftment occurred in 18 of 19 patients (95%). Pre-aDLI, 12 patients (63%) had bacteremia, nine of 17 at-risk patients (53%) reactivated CMV, and one developed acute GvHD. Sixteen patients received aDLI at dose levels 1 (103 T cells/kg, n = 4), 2 (104, n = 8), and 3 (105, n = 4). After aDLI, five patients developed clinically significant acute GvHD, and four of 14 at-risk patients (29%) reactivated CMV. T-cell recovery was significantly greater, and functional virus- and tumor-associated antigen-specific T cells were detectable earlier in patients receiving dose level 2 or 3 versus dose level 1/no aDLI. Alloanergization of donor cells expanded the CD4+ T-regulatory cell frequency within aDLI, which increased further in vivo without impeding expansion of virus- and tumor-associated antigen-specific T cells.Conclusions: These data demonstrate safety and a potential role for aDLI in contributing to immune reconstitution and expanding tolerogenic regulatory T cells in vivo after CD34-selected myeloablative haploidentical HSCT. Clin Cancer Res; 24(17); 4098–109. ©2018 AACR.