title: Donor CD4 T cells convert mixed to full donor T-cell chimerism and replenish the CD52-positive T-cell pool after alemtuzumab-based T-cell-depleted allo-transplantation.
abstract: Donor lymphocyte infusions (DLI) are used to resolve mixed T-cell chimerism (TCC) after allo-SCT despite a substantial risk of GVHD. We analyzed the impact of prophylactic CD8-depleted (CD8(depl)) DLI in 20 recipients of anti-CD52 alemtuzumab in vivo T-cell-depleted allografts with declining donor TCC after day +60. A total of 13 patients received CD8(depl) DLI and 7 patients did not. All but one of the DLI patients converted to complete donor T-cell chimeras, whereas only one non-DLI patient converted spontaneously. DLI induced transient acute GVHD in five and extensive chronic GVHD in two patients. These data suggest the use of CD8(depl) DLI as an effective treatment for mixed TCC, particularly in patients at high risk for GVHD. We also observed that the majority of reconstituting donor-derived T cells after alemtuzumab conditioning were CD52-negative. CD8(depl) DLI significantly increased the proportion of CD52-positive CD4 T cells, whereby their beneficial effect on reconstituting the post-transplant T-cell repertoire was shown.
authors.affiliation: Department of Medicine 3, Hematology and Oncology, Johannes Gutenberg-University, Mainz, Germany. r.meyer@3-med.klinik.uni-mainz.de
authors.forename: R G
authors.initials: RG
authors.lastname: Meyer
authors.forename: E M
authors.initials: EM
authors.lastname: Wagner
authors.forename: A
authors.initials: A
authors.lastname: Konur
authors.forename: K
authors.initials: K
authors.lastname: Bender
authors.forename: T
authors.initials: T
authors.lastname: Schmitt
authors.forename: J
authors.initials: J
authors.lastname: Hemmerling
authors.forename: D
authors.initials: D
authors.lastname: Wehler
authors.forename: U F
authors.initials: UF
authors.lastname: Hartwig
authors.forename: E
authors.initials: E
authors.lastname: Roosnek
authors.forename: C
authors.initials: C
authors.lastname: Huber
authors.forename: K
authors.initials: K
authors.lastname: Kolbe
authors.forename: W
authors.initials: W
authors.lastname: Herr
mesh_terms: D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000637:transplantation*; D000074301:CD52 Antigen; D049109:Cell Proliferation; D006023:Glycoproteins; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008212:Lymphocyte Depletion; D017710:Lymphocyte Transfusion / Q000379:methods*; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation; D016176:T-Lymphocyte Subsets; D018183:Transplantation Chimera / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins; D000074323:Alemtuzumab