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First Report of the Prophylactic Administration of Ex Vivo Co-Stimulated Donor Lymphocyte Infusion (DLI) from Related and Unrelated Donors after Reduced Intensity Conditioning for High Risk Hematologic Malignancies
Enhancing the graft versus tumor (GvT) effect without graft versus host disease (GvHD) is critical to the success of reduced intensity (RIC) strategies for allogeneic transplantation. Despite establishing donor lymphohematopoiesis, relapse rates remain high. Standard DLI given at relapse or prophyla...
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Published in: | Blood 2008-11, Vol.112 (11), p.468-468 |
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Main Authors: | , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Citations: | Items that cite this one |
Online Access: | Get full text |
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Summary: | Enhancing the graft versus tumor (GvT) effect without graft versus host disease (GvHD) is critical to the success of reduced intensity (RIC) strategies for allogeneic transplantation. Despite establishing donor lymphohematopoiesis, relapse rates remain high. Standard DLI given at relapse or prophylactically to enhance donor chimerism has met with limited success in improving transplant outcomes. Co-stimulation of donor T-cells, using anti-CD3/CD28 coated beads to serve as artificial APCs (IND #6914), may reverse functional T cell tolerance, thereby restoring immune responsiveness, potentiate GVT, and maintain remission. Unlike standard DLI, ex vivo co-stimulation may indirectly enhance T cell activity by removing and activating T cells outside of a potentially tumor-induced immunosuppressive milieu. We report the preliminary results of a ‘first in humans’ feasibility trial of ex vivo co-stimulated (activated/expanded) DLI from sibling and unrelated donors given ‘prophylactically’ at 4 and 6 months after RIC, T-cell depleted, allogeneic transplantation for patients (pts) with high-risk hematologic malignancy.
Methods: 15 pts have undergone RIC with alemtuzumab (100 mg SQ divided over D -9 to D-6), Fludarabine (30 mg/m2/d, D -6 to -3), Busulfan (0.8mg/kg IV Q6h D-4,-3) with peripheral blood stem cell transplantation (PBSCT) and planned activated DLI (pADLI) at 4 months (1 × 107 CD3+/kg recipient) and 6 months (1 × 108 CD3+/kg recipient) post-transplant in the absence of GvHD or relapse. All pts received tacrolimus and methotrexate as GvHD prophylaxis with initiation of rapid tacrolimus taper at ~d+40 and discontinuation before the infusion of pADLI#1.
Results: 8 pts (AML, secondary n=2; CR2 n=3; CR1 n=1; ALL CR1 n=1; CR2 n=1) received grafts from HLA-identical sibling donors, 7 (AML, secondary n=3; CR2 n=1; CR1 n=1; MDS, n=1; ALL, CR2 n=1) from 6/6 matched unrelated donors. Donor hematopoiesis (□ 90%D) was established in all patients. The median is f/u 272 days, (range 25–424d). Exvivo co-stimulation and expansion was successful in all products, except in one instance where the second infusion fell below the targeted dose. Of the 11 infusions given to date (both fresh and cryopreserved), there has been no infusion-related side effects or toxicity, confirming the safety and feasibility of this novel strategy. 8 pts have received the first of 2 planned infusions of pADLI from their original donor. Of the remaining 7 pts, 4 infusions are upcoming, 1 was preclud |
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ISSN: | 0006-4971 1528-0020 |
DOI: | 10.1182/blood.V112.11.468.468 |