Infusion of Alloanergized Donor Lymphocytes after CD34-selected Haploidentical Myeloablative Hematopoietic Stem Cell Transplantation
| العنوان: | Infusion of Alloanergized Donor Lymphocytes after CD34-selected Haploidentical Myeloablative Hematopoietic Stem Cell Transplantation |
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| المؤلفون: | Eva C. Guinan, John R. Wingard, Christopher R. Cogle, Peter F. Thall, Laurence J.N. Cooper, Bimalangshu R. Dey, Lisa L. Brennan, Neena Kapoor, Ami J. Shah, Thomas R. Spitzer, Richard E. Champlin, Jeff K. Davies, Lee M. Nadler, Marcos de Lima |
| المصدر: | Clinical Cancer Research. 24:4098-4109 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Adult, CD4-Positive T-Lymphocytes, Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Transplantation Conditioning, Lymphocyte Transfusion, T-Lymphocytes, medicine.medical_treatment, Graft vs Host Disease, Antigens, CD34, Hematopoietic stem cell transplantation, Article, Donor lymphocyte infusion, 03 medical and health sciences, 0302 clinical medicine, Immune system, Internal medicine, medicine, Humans, Transplantation, Homologous, Lymphocytes, Acute leukemia, Leukemia, business.industry, Hematopoietic Stem Cell Transplantation, Middle Aged, Myeloablative Agonists, Donor Lymphocytes, Immunity, Innate, Tissue Donors, Transplantation, surgical procedures, operative, 030104 developmental biology, Myelodysplastic Syndromes, Transplantation, Haploidentical, Female, business, 030215 immunology |
| الوصف: | 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. |
| تدمد: | 1557-3265 1078-0432 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dad2de6af3524ef109381766423d7266 https://doi.org/10.1158/1078-0432.ccr-18-0449 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....dad2de6af3524ef109381766423d7266 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15573265 10780432 |
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