Prophylactic transfer of CD8-depleted donor lymphocytes after T-cell–depleted reduced-intensity transplantation
| Autor: | Abdo Konur, Thomas Wehler, Klaus Bender, Daniela Wehler, Georg Hess, Udo F. Hartwig, Cedrik M. Britten, Chiara Gentilini, Ralf G. Meyer, Christoph Huber, Lutz Uharek, Wolfgang Herr, Karin Kolbe, Andrew J. Ullmann |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Adult
Male Transplantation Conditioning CD52 Antibodies Neoplasm medicine.medical_treatment T cell Immunology Graft vs Host Disease Hematopoietic stem cell transplantation CD8-Positive T-Lymphocytes Antibodies Monoclonal Humanized Immunotherapy Adoptive Biochemistry Lymphocyte Depletion HLA Antigens medicine Humans Cytotoxic T cell Alemtuzumab Peripheral Blood Stem Cell Transplantation Immunomagnetic Separation business.industry Graft Survival Antibodies Monoclonal Cell Biology Hematology Middle Aged Donor Lymphocytes medicine.disease Transplantation Treatment Outcome surgical procedures operative Graft-versus-host disease medicine.anatomical_structure Hematologic Neoplasms Langerhans Cells Female K562 Cells business Follow-Up Studies medicine.drug |
| Zdroj: | Blood. 109:374-382 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Allogeneic hematopoietic stem cell transplantation (SCT) regimens incorporating the lymphocytotoxic CD52 antibody alemtuzumab demonstrate efficient engraftment and reduced graft-versus-host disease (GVHD). However, these protocols substantially impair posttransplantation antiviral and antitumor immunity. To accelerate immune reconstitution after alemtuzumab-based reduced-intensity SCT, we administered prophylactic CD8-depleted donor lymphocyte infusions (DLIs) starting on days 60 and 120 after transplantation. DLIs were processed in an immunomagnetic good manufacturing practice depletion procedure resulting in a 2.5- to 6-log reduction in CD8 T cells. Of 23 high-risk patients with hematologic malignancies, 11 received a total of 21 CD8-depleted DLIs. Five patients developed transient grade I acute GVHD following transfer. Only 2 patients with HLA-C–mismatched donors showed grade II and III acute GVHD and subsequently progressed to limited chronic GVHD. Following DLIs, 4 patients with declining hematopoietic donor chimerism converted to full chimeras. A 2.1-fold median increase of circulating CD4 T cells was observed within 2 weeks after infusion. Non-DLI patients did not show a comparable rise in CD4 counts. Four patients demonstrated enhanced frequencies of cytomegalovirus-specific CD4 and CD8 T cells following transfer. Our results suggest that prophylactic CD8-depleted DLIs accelerate immune reconstitution after lymphodepleted HLA-matched SCT and carry a low risk of inducing severe GVHD. |
| Databáze: | OpenAIRE |
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