title: Comparison of different rabbit ATG preparation effects on early lymphocyte subset recovery after allogeneic HSCT and its association with EBV-mediated PTLD.
abstract: OBJECTIVE
  Rabbit antithymocyte globulin (ATG) is commonly used before allogeneic hematopoietic stem cell transplantation (allo-HSCT) to prevent graft-versus-host disease. Studies comparing the effect of different ATG preparations and dosages on immune reconstitution and risk for Epstein-Barr virus (EBV)-mediated post-transplant lymphoproliferative disorder (PTLD) are rare.
  
  
  METHODS
  In this retrospective study, we determined T and B cell subsets by flow cytometry after allo-HSCT in children, who received ATG-Genzyme (ATG-G, n = 15), ATG-Fresenius (ATG-F, n = 25) or no-ATG treatment (n = 19). Additionally, PCR-quantified EBV-genome copy counts were correlated with incidence of PTLD.
  
  
  RESULTS
  We could confirm a dose-dependent impairment of CD8(+) and CD4(+) T cell regeneration by ATG-G, including naïve and memory CD4(+) T cells. No differences were seen between the currently applied dosages of 5-10 mg/kg ATG-G and 20-60 mg/kg ATG-F. Significantly delayed T cell subset reconstitution was determined only at high dosages of 20-60 mg/kg ATG-G compared to ATG-F. B cell reconstitution was comparably impaired in ATG-G- and ATG-F-treated patients. Although the incidence of EBV reactivation was similar in both ATG groups, EBV copy counts of >10(4) copies/10(5) peripheral blood mononuclear cells and the occurrence of PTLD were only found in ATG-G-treated patients.
  
  
  CONCLUSIONS
  We conclude that high, but importantly not currently applied low dosages of ATG-G, impair thymic T cell regeneration and memory T cell immunity to a greater extent than ATG-F in pediatric patients. In addition, our results suggest an increased risk for EBV-PTLD when treated with ATG-G. Prospective studies are warranted to compare different ATG preparations with regard to the immune reconstitution and EBV-PTLD.
authors: Institute of Medical Immunology, Charité CVK, Berlin, Germany.
authors: Angela
authors: A
authors: Mensen
authors: Il-Kang
authors: IK
authors: Na
authors: Ralf
authors: R
authors: Häfer
authors: Astrid
authors: A
authors: Meerbach
authors: Maria
authors: M
authors: Schlecht
authors: Marie-Luise
authors: ML
authors: Pietschmann
authors: Bernd
authors: B
authors: Gruhn
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D020031:Epstein-Barr Virus Infections / Q000276:immunology*; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007223:Infant; D007938:Leukemia / Q000628:therapy; D008232:Lymphoproliferative Disorders / Q000821:virology*; D008297:Male; D011817:Rabbits; D012189:Retrospective Studies; D012306:Risk; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014184:Transplantation, Homologous; D014775:Virus Activation; D055815:Young Adult
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents