title: Prophylactic transfer of CD8-depleted donor lymphocytes after T-cell-depleted reduced-intensity transplantation.
abstract: 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.
authors.affiliation: Department of Medicine III, Hematology and Oncology, Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Ralf G
authors.initials: RG
authors.lastname: Meyer
authors.forename: Cedrik M
authors.initials: CM
authors.lastname: Britten
authors.forename: Daniela
authors.initials: D
authors.lastname: Wehler
authors.forename: Klaus
authors.initials: K
authors.lastname: Bender
authors.forename: Georg
authors.initials: G
authors.lastname: Hess
authors.forename: Abdo
authors.initials: A
authors.lastname: Konur
authors.forename: Udo F
authors.initials: UF
authors.lastname: Hartwig
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Wehler
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Ullmann
authors.forename: Chiara
authors.initials: C
authors.lastname: Gentilini
authors.forename: Lutz
authors.initials: L
authors.lastname: Uharek
authors.forename: Christoph
authors.initials: C
authors.lastname: Huber
authors.forename: Karin
authors.initials: K
authors.lastname: Kolbe
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Herr
mesh_terms: D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology; D006680:HLA Antigens / Q000276:immunology; D019337:Hematologic Neoplasms / Q000601:surgery*; D006801:Humans; D018189:Immunomagnetic Separation; D016219:Immunotherapy, Adoptive; D020014:K562 Cells / Q000276:immunology; D007801:Langerhans Cells / Q000473:pathology; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects; D019172:Transplantation Conditioning / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D006680:HLA Antigens; D000074323:Alemtuzumab