Journal of Research in Pharmacy Practice

The risk factors for cytomegalovirus reactivation following stem cell transplantation

Authors

. Bahareh Valadkhani 1
. Mona Kargar 2
. Asieh Ashouri 3
. Molouk Hadjibabaie 2
. Kheirollah Gholami 2
. Ardeshir Ghavamzadeh 4

1 Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

2 Research Center for Rational Use of Drugs, Tehran University of Medical Sciences, Tehran, Iran

3 School of Health, Guilan University of Medical Sciences, Rasht, Iran

4 Department of Hematology‑Oncology, Hematology‑Oncology and SCT Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

Abstract
Objective: Opportunistic infections like cytomegalovirus (CMV) are among the 
primary causes of morbidity and mortality in patients undergoing hematipoetic stem 
cell transplantation (HSCT). This infection is frequently seen in early postengraftment 
period. So we determined to find the risk factors associated with CMV reactivation.
Methods: We retrospectively evaluated the medical records of 126 consecutive patients 
who underwent allogenic‑HSCT from peripheral blood stem cells from August 2011 to 
February 2013 in Shariati Hospital. We included HSCT patients with 15 years of age 
or older, who survived at least 100 days after transplantation. CMV reactivation was 
detected based on the weekly PP65 assessment. Patients with 10 or more positive cells 
per 50,000 cells were defined as having high‑level antigenemia.
Findings: From 126 patients which included in this study, 76 were male (60%). CMV 
antigenemia was documented in 43 patients (34%). The median time to CMV infection 
was 40 days (range: 3–77) after transplantation. The incidence of high‑level antigenemia 
during the first 100 days following HSCT was 11%.
Conclusion: We found that the significant risk factor for CMV antigenemia in multivariate 
analysis was prior graft‑versus‑host disease (GVHD) experience and higher donor age. For 
high‑level antigenemia, GVHD or duration of its treatment was significant determinant.

Keywords

Allogeneic hematopoietic stem cell transplantation
cytomegalovirus  infection
graft‑versus‑host disease
1. Costanzo ES, Juckett MB, Coe CL. Biobehavioral influences on 
recovery following hematopoietic stem cell transplantation. 
Brain Behav Immun 2013;30 Suppl: S68‑74.
2. Wingard JR. Opportunistic infections after blood and marrow 
transplantation. Transpl Infect Dis 1999;1:3‑20.
3. Watcharananan SP, Kiertiburanakul S, Piyatuctsanawong W, 
Anurathapan U, Sungkanuparph S, Pakakasama S, 
et al. Cytomegalovirus, adenovirus, and polyomavirus 
co‑infection among pediatric recipients of allogeneic stem 
cell transplantation: Characteristics and outcome. Pediatr 
Transplant 2010;14:675‑81.
4. Reinke P, Prösch S, Kern F, Volk HD. Mechanisms of human 
cytomegalovirus (HCMV) (re) activation and its impact on 
organ transplant patients. Transpl Infect Dis 1999;1:157‑64.
5. PeresRM, CostaCR, AndradePD, BononSH, AlbuquerqueDM, 
de OliveiraC, etal. Surveillance of active human cytomegalovirus 
infection in hematopoietic stem cell transplantation (HLA 
sibling identical donor): Search for optimal cutoff value by 
real‑time PCR. BMC Infect Dis 2010;10:147.
6. Ksouri H, Eljed H, GrecoA, LakhalA, Torjman L, AbdelkefiA, et al. Analysis of cytomegalovirus (CMV) viremia using 
the pp65 antigenemia assay, the amplicor CMV test, and 
a semi‑quantitative polymerase chain reaction test after 
allogeneic marrow transplantation. Transpl Infect Dis 
2007;9:16‑21.
7. Borchers S, Luther S, Lips U, Hahn N, Kontsendorn J, 
Stadler M, et al. Tetramer monitoring to assess risk factors for 
recurrent cytomegalovirus reactivation and reconstitution of 
antiviral immunity post allogeneic hematopoietic stem cell 
transplantation. Transpl Infect Dis 2011;13:222‑36.
8. Kim DH, Kim JG, Lee NY, Sung WJ, Sohn SK, Suh JS, et al.
Risk factors for late cytomegalovirus infection after allogeneic 
stem cell transplantation using HLA‑matched sibling donor: 
Donor lymphocyte infusion and previous history of early 
CMV infection. Bone Marrow Transplant 2004;34:21‑7.
9. Barkholt L, Lewensohn‑Fuchs I, Ericzon BG, Tydén G, 
Andersson J. High‑dose acyclovir prophylaxis reduces 
cytomegalovirus disease in liver transplant patients. Transpl 
Infect Dis 1999;1:89‑97.
10. Ljungman P, Hakki M, Boeckh M. Cytomegalovirus in 
hematopoietic stem cell transplant recipients. Infect Dis Clin 
North Am 2010;24:319‑37.
11. Cho BS, Yahng SA, Kim JH, Yoon JH, Shin SH, Lee SE, 
et al. Impact of cytomegalovirus gastrointestinal disease 
on the clinical outcomes in patients with gastrointestinal 
graft‑versus‑host disease in the era of preemptive therapy. 
Ann Hematol 2013;92:497‑504.
12. El‑Cheikh J, Devillier R, Crocchiolo R, Fürst S, Calmels B, 
Faucher C, et al. Impact of pretransplant donor and recipient 
cytomegalovirus serostatus on outcome for multiple myeloma 
patients undergoing reduced intensity conditioning allogeneic 
stem cell transplantation. Mediterr J Hematol Infect Dis 
2013;5:e2013026.
13. George B, Pati N, Gilroy N, Ratnamohan M, Huang G, 
Kerridge I, et al. Pre‑transplant cytomegalovirus (CMV) 
serostatus remains the most important determinant of 
CMV reactivation after allogeneic hematopoietic stem cell 
transplantation in the era of surveillance and preemptive 
therapy. Transpl Infect Dis 2010;12:322‑9.
14. George B, Kerridge IH, Gilroy N, Huang G, Hertzberg MS, 
Bradstock KF, et al. A risk score for early cytomegalovirus 
reactivation after allogeneic stem cell transplantation identifies 
low‑, intermediate‑, and high‑risk groups: Reactivation 
risk is increased by graft‑versus‑host disease only in the 
intermediate‑risk group. Transpl Infect Dis 2012;14:141‑8.
15. Miller W, Flynn P, McCullough J, Balfour HH Jr, Goldman A, 
Haake R, et al. Cytomegalovirus infection after bone marrow 
transplantation: An association with acute graft‑v‑host disease. 
Blood 1986;67:1162‑7.
16. Yanada M, Yamamoto K, Emi N, Naoe T, Suzuki R, Taji H, 
et al. Cytomegalovirus antigenemia and outcome of 
patients treated with pre‑emptive ganciclovir: Retrospective 
analysis of 241 consecutive patients undergoing allogeneic 
hematopoietic stem cell transplantation. Bone Marrow 
Transplant 2003;32:801‑7.
17. Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, 
Clift RA, et al. Clinical manifestations of graft‑versus‑host 
disease in human recipients of marrow from HL‑A‑matched 
sibling donors. Transplantation 1974;18:295‑304.
18. Kanda Y, Mineishi S, Saito T, Seo S, Saito A, Suenaga K, 
et al. Pre‑emptive therapy against cytomegalovirus (CMV) 
disease guided by CMV antigenemia assay after allogeneic 
hematopoietic stem cell transplantation: A single‑center 
experience in Japan. Bone Marrow Transplant 2001;27:437‑44.
19. Serio B, Rosamilio R, Giudice V, Pepe S, Zeppa P, Esposiito S, 
et al. Low‑dose valgancyclovir as cytomegalovirus 
reactivation prophylaxis in allogeneic haematopoietic stem 
cell transplantation. Infez Med 2012;20 Suppl 2:26‑34.
20. Cantoni N, Hirsch HH, Khanna N, Gerull S, BuserA, Bucher C, 
et al. Evidence for a bidirectional relationship between 
cytomegalovirus replication and acute graft‑versus‑host 
disease. Biol Blood Marrow Transplant 2010;16:1309‑14.
21. Schetelig J, Oswald O, Steuer N, RadonicA, Thulke S, Held TK, 
et al. Cytomegalovirus infections in allogeneic stem cell 
recipients after reduced‑intensity or myeloablative conditioning 
assessed by quantitative PCR and pp65‑antigenemia. Bone 
Marrow Transplant 2003;32:695‑701.
22. Ljungman P, Perez‑Bercoff L, Jonsson J, Avetisyan G, 
Sparrelid E, Aschan J, et al. Risk factors for the development 
of cytomegalovirus disease after allogeneic stem cell 
transplantation. Haematologica 2006;91:78‑83.
23. Ross SA, Novak Z, Pati S, Boppana SB. Overview of the 
diagnosis of cytomegalovirus infection. Infect Disord Drug 
Targets 2011;11:466‑74.
Journal of Research in Pharmacy Practice
Volume 5, Issue 1
Winter 2016
Pages 63-69

Home

Guide for Authors

Submit Manuscript

Reviewers

Contact Us