title: Evaluation of the validity of preemptive therapy against cytomegalovirus disease based on antigenemia assay with a cutoff of 20 positive cells per two slides.
abstract: BACKGROUND
  Preemptive therapy with ganciclovir (GCV) based on the results of a cytomegalovirus (CMV) antigenemia assay is a standard strategy for preventing CMV disease after allogeneic hematopoietic cell transplantation (HCT). However, the appropriate threshold of antigenemia-positive cells for deciding when to start GCV remains unclear.
  
  
  METHODS
  This retrospective study included 80 recipients who received HCT from an alternative donor between 2007 and 2011. In 2009, we switched the threshold from 3 (3A group, n=24) to 20 (20A group, n=56) antigenemia-positive cells per two slides for preemptive therapy after HCT from an alternative donor.
  
  
  RESULTS
  Early CMV disease within 100 days after HCT was observed in one patient in the 20A group. Antiviral agents including GCV, val-GCV, and foscarnet were given in 17 (71%) and 36 (64%) patients in the 3A and 20A groups, respectively (p=0.23). In 13 (23%) patients in the 20A group, the initiation of preemptive therapy was avoided because of the change in the cutoff value for CMV antigenemia. However, the total dose of GCV was not different between the two groups. The use of steroid was significantly associated with CMV antigenemia of at least 20 positive cells among patients with low-level antigenemia at the first detection.
  
  
  CONCLUSIONS
  The increased threshold up to 20 positive cells for starting preemptive therapy was not associated with a significant increase in CMV disease, but the total dose of GCV was not reduced and there was one early CMV disease in the 20A group. We should explore how to identify patients who are at high risk for increased antigenemia among patients with low-level antigenemia, but at least, preemptive therapy should not be withheld in patients who are already receiving systemic steroid.
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakasone
authors.forename: Hidenori
authors.initials: H
authors.lastname: Wada
authors.forename: Ryoko
authors.initials: R
authors.lastname: Yamasaki
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ishihara
authors.forename: Koji
authors.initials: K
authors.lastname: Kawamura
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ashizawa
authors.forename: Miki
authors.initials: M
authors.lastname: Sato
authors.forename: Kiriko
authors.initials: K
authors.lastname: Terasako-Saito
authors.forename: Tomohito
authors.initials: T
authors.lastname: Machishima
authors.forename: Shun-ichi
authors.initials: S
authors.lastname: Kimura
authors.forename: Misato
authors.initials: M
authors.lastname: Kikuchi
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kako
authors.forename: Junya
authors.initials: J
authors.lastname: Kanda
authors.forename: Rie
authors.initials: R
authors.lastname: Yamazaki
authors.forename: Aki
authors.initials: A
authors.lastname: Tanihara
authors.forename: Junji
authors.initials: J
authors.lastname: Nishida
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kanda
mesh_terms: D000293:Adolescent; D000328:Adult; D000956:Antigens, Viral / Q000097:blood / Q000276:immunology; D000998:Antiviral Agents / Q000627:therapeutic use*; D001782:Blood Donors; D003131:Combined Modality Therapy; D003587:Cytomegalovirus / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000628:therapy* / Q000821:virology; D005260:Female; D017245:Foscarnet / Q000627:therapeutic use; D015774:Ganciclovir / Q000627:therapeutic use; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care / Q000379:methods; D015203:Reproducibility of Results; D012189:Retrospective Studies; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D000956:Antigens, Viral; D000998:Antiviral Agents; D017245:Foscarnet; D015774:Ganciclovir
references.citation: Bone Marrow Transplant. 2001 Feb;27(4):437-44
references.pmid: 11313674
references.citation: Bone Marrow Transplant. 2008 May;41(10):873-9
references.pmid: 18209721
references.citation: Bone Marrow Transplant. 2010 Aug;45(8):1325-32
references.pmid: 19966850
references.citation: Bone Marrow Transplant. 2004 Feb;33(4):431-4
references.pmid: 14676775
references.citation: J Antimicrob Chemother. 2006 May;57(5):1004-7
references.pmid: 16551692
references.citation: Bone Marrow Transplant. 2013 Mar;48(3):452-8
references.pmid: 23208313
references.citation: Blood. 2012 Mar 8;119(10):2409-16
references.pmid: 22042692
references.citation: Int J Hematol. 2008 Apr;87(3):310-8
references.pmid: 18320138
references.citation: Biol Blood Marrow Transplant. 2003 Sep;9(9):543-58
references.pmid: 14506657
references.citation: Bone Marrow Transplant. 1997 Feb;19(3):241-8
references.pmid: 9028553
references.citation: Clin Pharmacokinet. 1999 Aug;37(2):167-76
references.pmid: 10496303
references.citation: Blood. 2009 Jun 4;113(23):5711-9
references.pmid: 19299333
references.citation: Blood. 1995 Oct 1;86(7):2815-20
references.pmid: 7670117
references.citation: Transplant Proc. 1996 Jun;28(3):1750-3
references.pmid: 8658867
references.citation: Blood. 1996 Nov 15;88(10):4063-71
references.pmid: 8916975
references.citation: Clin Infect Dis. 2002 Apr 15;34(8):1094-7
references.pmid: 11914998
references.citation: Transplantation. 2002 Feb 27;73(4):568-72
references.pmid: 11889432
references.citation: Biol Blood Marrow Transplant. 2006 Jun;12(6):635-40
references.pmid: 16737936
references.citation: Antimicrob Agents Chemother. 2000 Oct;44(10):2811-5
references.pmid: 10991864
references.citation: Bone Marrow Transplant. 2002 Sep;30(5):315-9
references.pmid: 12209354
references.citation: Bone Marrow Transplant. 2004 Jun;33(11):1075-81
references.pmid: 15077131