title: Serotherapy with thymoglobulin and alemtuzumab differentially influences frequency and function of natural killer cells after allogeneic stem cell transplantation.
abstract: Although thymoglobulin and alemtuzumab are frequently used in hematopoietic stem cell transplantation (HSCT), little is known of their effects on NK cells, which mediate important functions in post-transplantation immunology. In the present study, we determined NK cell death in vitro using propidium iodide and Annexin V. The NK cell activity in 34 patients at day +30 after allogeneic HSCT was assessed using the CD107a assay. Alemtuzumab and thymoglobulin were similarly very potent in inducing NK cell death in vitro. Even in low concentrations (<1 microg/ml) the antibodies induced apoptosis and necrosis in a relevant percentage of NK cells (>30%). However, the number of tumor reactive (CD107a+) NK cells was 13.16 per mul and 1.15 per microl (mean) in patients receiving T-cell depletion with 6 mg/kg thymoglobulin and in patients receiving 100 mg alemtuzumab, respectively (P=0.02). Although thymoglobulin and alemtuzumab are equally NK cell toxic in vitro, the recovery of NK cell frequency and anti-tumor reactivity is reduced in recipients of alemtuzumab. Our findings can be explained by a longer half-life of alemtuzumab as compared to active thymoglobulin under therapeutic conditions. Prolonged immunosuppression with increased risk of infections and tumor relapse are a potential threat to patients undergoing HCST and receiving alemtuzumab as T-cell depletion.
authors.affiliation: Department of Hematology, Oncology, and Transfusion Medicine, Charité, Berlin, Germany. penacko@mskcc.org
authors.forename: O
authors.initials: O
authors.lastname: Penack
authors.forename: L
authors.initials: L
authors.lastname: Fischer
authors.forename: A
authors.initials: A
authors.lastname: Stroux
authors.forename: C
authors.initials: C
authors.lastname: Gentilini
authors.forename: A
authors.initials: A
authors.lastname: Nogai
authors.forename: A
authors.initials: A
authors.lastname: Muessig
authors.forename: K
authors.initials: K
authors.lastname: Rieger
authors.forename: S
authors.initials: S
authors.lastname: Ganepola
authors.forename: W
authors.initials: W
authors.lastname: Herr
authors.forename: R G
authors.initials: RG
authors.lastname: Meyer
authors.forename: E
authors.initials: E
authors.lastname: Thiel
authors.forename: L
authors.initials: L
authors.lastname: Uharek
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000494:pharmacology*; D000961:Antilymphocyte Serum; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects*; D008212:Lymphocyte Depletion / Q000009:adverse effects*; D008875:Middle Aged; D014184:Transplantation, Homologous
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D000074323:Alemtuzumab; C512542:thymoglobulin