Infusion of Alloanergized Donor Lymphocytes after CD34-selected Haploidentical Myeloablative Hematopoietic Stem Cell Transplantation

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Jeff K DaviesEva C Guinan

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...Continue Reading

References

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Sep 2, 2004·Biometrics·Peter F Thall, John D Cook
Mar 9, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Franco AversaMassimo F Martelli
Dec 13, 2005·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Alexandra H FilipovichMary E D Flowers
May 21, 2008·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Leo LuznikEphraim J Fuchs
Apr 7, 2010·Science Translational Medicine·Jeffrey K DaviesEva C Guinan

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Citations

Oct 9, 2019·Current Opinion in Oncology·Gaurav Sutrave, David J Gottlieb
Aug 27, 2019·Frontiers in Immunology·Ping Zhang, Siok-Keen Tey

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