title: Immune reconstitution and cytomegalovirus infection after allogeneic stem cell transplantation: the important impact of in vivo T cell depletion.
abstract: We analyzed cytomegalovirus (CMV) infection risk factors and immune reconstitution kinetics in 89 patients after allogeneic stem cell transplantation (allo-SCT). The use of alemtuzumab for in vivo T cell depletion (TCD) had, besides the donor/recipient CMV serostatus, the strongest influence on the CMV infection risk in univariate and multivariate analyses. In comparison to without use of in vivo TCD, the CMV infection risk [hazard ratio (HR)] was 4.82-fold after TCD with alemtuzumab, but only 1.40-fold after TCD with antithymocyte globulin (ATG). Alemtuzumab strongly depressed CD4(+) and CD8(+) T cell reconstitution, whereas ATG only delayed CD4(+) T cell reconstitution. Considering the reconstitution kinetics of CD4(+) and CD8(+) T cells, CMV-specific CD8(+) T cells, NK cells and the IgG concentration, only a low day +60 NK cell count (< or =161 versus >161/microl) was significantly associated with CMV infection development (HR 2.92, p = 0.034). CMV-specific CD8(+) T cells were detected in 57% of patients with a CMV-seropositive donor, but in none of the patients with a CMV-seronegative donor on day +30 (p = 0.01). Our data indicate that the type of in vivo TCD (alemtuzumab or ATG) differentially influences both the CMV infection risk and CD4(+)/CD8(+) T cell reconstitution kinetics in patients after allo-SCT.
authors.affiliation: Medical Department III (Hematology, Oncology and Transfusion Medicine), Charité Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany. martin.schmidt-hieber@charite.de
authors.forename: Martin
authors.initials: M
authors.lastname: Schmidt-Hieber
authors.forename: S
authors.initials: S
authors.lastname: Schwarck
authors.forename: A
authors.initials: A
authors.lastname: Stroux
authors.forename: S
authors.initials: S
authors.lastname: Ganepola
authors.forename: P
authors.initials: P
authors.lastname: Reinke
authors.forename: E
authors.initials: E
authors.lastname: Thiel
authors.forename: L
authors.initials: L
authors.lastname: Uharek
authors.forename: I W
authors.initials: IW
authors.lastname: Blau
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000009:adverse effects / Q000627:therapeutic use; D000961:Antilymphocyte Serum / Q000009:adverse effects / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000209:etiology*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000276:immunology; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D000074323:Alemtuzumab