title: Sequential anti-cytomegalovirus response monitoring may allow prediction of cytomegalovirus reactivation after allogeneic stem cell transplantation.
abstract: BACKGROUND
  Reconstitution of cytomegalovirus-specific CD3(+)CD8(+) T cells (CMV-CTLs) after allogeneic hematopoietic stem cell transplantation (HSCT) is necessary to bring cytomegalovirus (CMV) reactivation under control. However, the parameters determining protective CMV-CTL reconstitution remain unclear to date.
  
  
  METHODS
  In a prospective tri-center study, CMV-CTL reconstitution was analyzed in the peripheral blood from 278 patients during the year following HSCT using 7 commercially available tetrameric HLA-CMV epitope complexes. All patients included could be monitored with at least CMV-specific tetramer.
  
  
  RESULTS
  CMV-CTL reconstitution was detected in 198 patients (71%) after allogeneic HSCT. Most importantly, reconstitution with 1 CMV-CTL per µl blood between day +50 and day +75 post-HSCT discriminated between patients with and without CMV reactivation in the R+/D+ patient group, independent of the CMV-epitope recognized. In addition, CMV-CTLs expanded more daramtaically in patients experiencing only one CMV-reactivation than those without or those with multiple CMV reactivations. Monitoring using at least 2 tetramers was possible in 63% (n = 176) of the patients. The combinations of particular HLA molecules influenced the numbers of CMV-CTLs detected. The highest CMV-CTL count obtained for an individual tetramer also changed over time in 11% of these patients (n = 19) resulting in higher levels of HLA-B*0801 (IE-1) recognizing CMV-CTLs in 14 patients.
  
  
  CONCLUSIONS
  Our results indicate that 1 CMV-CTL per µl blood between day +50 to +75 marks the beginning of an immune response against CMV in the R+/D+ group. Detection of CMV-CTL expansion thereafter indicates successful resolution of the CMV reactivation. Thus, sequential monitoring of CMV-CTL reconstitution can be used to predict patients at risk for recurrent CMV reactivation.
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Borchers
authors.forename: Melanie
authors.initials: M
authors.lastname: Bremm
authors.forename: Thomas
authors.initials: T
authors.lastname: Lehrnbecher
authors.forename: Elke
authors.initials: E
authors.lastname: Dammann
authors.forename: Brigitte
authors.initials: B
authors.lastname: Pabst
authors.forename: Benno
authors.initials: B
authors.lastname: Wölk
authors.forename: Ruth
authors.initials: R
authors.lastname: Esser
authors.forename: Meral
authors.initials: M
authors.lastname: Yildiz
authors.forename: Matthias
authors.initials: M
authors.lastname: Eder
authors.forename: Michael
authors.initials: M
authors.lastname: Stadler
authors.forename: Peter
authors.initials: P
authors.lastname: Bader
authors.forename: Hans
authors.initials: H
authors.lastname: Martin
authors.forename: Andrea
authors.initials: A
authors.lastname: Jarisch
authors.forename: Gisbert
authors.initials: G
authors.lastname: Schneider
authors.forename: Thomas
authors.initials: T
authors.lastname: Klingebiel
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.forename: Eva M
authors.initials: EM
authors.lastname: Weissinger
authors.forename: Ulrike
authors.initials: U
authors.lastname: Koehl
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017252:CD3 Complex / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D002648:Child; D002675:Child, Preschool; D003587:Cytomegalovirus / Q000378:metabolism*; D003586:Cytomegalovirus Infections / Q000175:diagnosis* / Q000378:metabolism; D000939:Epitopes / Q000737:chemistry; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D007223:Infant; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012306:Risk; D014184:Transplantation, Homologous / Q000379:methods
chemical_list: D017252:CD3 Complex; D000939:Epitopes