Prophylactic transfer of CD8-depleted donor lymphocytes after T-cell–depleted reduced-intensity transplantation

• Published in: Blood 2007-01, Vol.109 (1), p.374-382
• Main Authors: Meyer, Ralf G., Britten, Cedrik M., Wehler, Daniela, Bender, Klaus, Hess, Georg, Konur, Abdo, Hartwig, Udo F., Wehler, Thomas C., Ullmann, Andrew J., Gentilini, Chiara, Uharek, Lutz, Huber, Christoph, Kolbe, Karin, Herr, Wolfgang
• Format: Article
• Language: English
• Subjects: Adult; Alemtuzumab; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm - pharmacology; Biological and medical sciences; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - transplantation; Female; Follow-Up Studies; Graft Survival; Graft vs Host Disease - etiology; Hematologic and hematopoietic diseases; Hematologic Neoplasms - surgery; HLA Antigens - immunology; Humans; Immunomagnetic Separation; Immunotherapy, Adoptive; K562 Cells - immunology; Langerhans Cells - pathology; Lymphocyte Depletion; Male; Medical sciences; Middle Aged; Peripheral Blood Stem Cell Transplantation - adverse effects; Transplantation Conditioning - methods; Treatment Outcome
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2006-03-005769

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.