Antiviral prophylaxis for cytomegalovirus infection in allogeneic hematopoietic cell transplantation

被引:92
作者
Chen, Kaiwen [1 ,2 ]
Cheng, Matthew P. [1 ,2 ]
Hammond, Sarah P. [1 ,2 ]
Einsele, Hermann [3 ]
Marty, Francisco M. [1 ,2 ]
机构
[1] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA
[2] Harvard Med Sch, Brigham & Womens Hosp, Div Infect Dis, Boston, MA USA
[3] Univ Klinikum Wurzburg, Dept Internal Med 2, Wurzburg, Germany
关键词
LONG-TERM ACYCLOVIR; COMPOUND AIC246 LETERMOVIR; POLYMERASE-CHAIN-REACTION; STEM-CELL; DOUBLE-BLIND; IN-VITRO; T-CELLS; OVERLAPPING PENTADECAPEPTIDES; INTRAVENOUS GANCICLOVIR; MARIBAVIR PROPHYLAXIS;
D O I
10.1182/bloodadvances.2018016493
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Patients treated with allogeneic hematopoietic cell transplantation (HCT) are at risk of cytomegalovirus (CMV) reactivation and disease, which results in increased morbidity and mortality. Although universal antiviral prophylaxis against CMV improves outcomes in solid organ transplant recipients, data have been conflicting regarding such prophylaxis in patients undergoing allogeneic HCT. We conducted a systematic review of randomized trials of prophylactic antivirals against CMV after allogeneic HCT to summarize the evolution of the field over the last 35 years and evaluate the prophylactic potential of antiviral agents against CMV after allogeneic HCT. Electronic databases were queried from database inception through 31 December 2017. For included studies, incidence of CMV infection and all-cause mortality were collected as primary outcomes; CMV disease incidence, use of preemptive therapy, and drug toxicities were collected as secondary outcomes. Nineteen clinical trials conducted between 1981 and 2017 involving a total of 4173 patients were included for review. Prophylactic strategies included use of acyclovir, valacyclovir, ganciclovir, maribavir, brincidofovir, and letermovir compared with placebo or a comparator antiviral. Fourteen trials that compared antiviral prophylaxis with placebo demonstrated overall effectiveness in reducing incidence of CMV infection (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.42-0.58), CMV disease (OR, 0.56; 95% CI, 0.40-0.80), and use of preemptive therapy (OR, 0.51; 95% CI, 0.42-0.62; 6 trials); however, none demonstrated reduction in all-cause mortality (OR, 0.96; 95% CI, 0.78-1.18) except the phase 3 trial of letermovir (week-24 OR, 0.59; 95% CI, 0.38-0.98). Additional research is warranted to determine patient groups most likely to benefit from antiviral prophylaxis and its optimal deployment after allogeneic HCT.
引用
收藏
页码:2159 / 2175
页数:17
相关论文
共 80 条
[1]   Cyclosporine A, but Not Tacrolimus, Shows Relevant Inhibition of Organic Anion-Transporting Protein 1B1-Mediated Transport of Atorvastatin [J].
Amundsen, Rune ;
Christensen, Hege ;
Zabihyan, Behnaz ;
Asberg, Anders .
DRUG METABOLISM AND DISPOSITION, 2010, 38 (09) :1499-1504
[2]  
[Anonymous], 2014, REV MAN REVMAN COMP
[3]   Cytomegalovirus Seroprevalence in the United States: The National Health and Nutrition Examination Surveys, 1988-2004 [J].
Bate, Sheri Lewis ;
Dollard, Sheila C. ;
Cannon, Michael J. .
CLINICAL INFECTIOUS DISEASES, 2010, 50 (11) :1439-1447
[4]   Long-term acyclovir for prevention of varicella zoster virus disease after allogeneic hematopoietic cell transplantation - a randomized double-blind placebo-controlled study [J].
Boeckh, M ;
Kim, HW ;
Flowers, MED ;
Meyers, JD ;
Bowden, RA .
BLOOD, 2006, 107 (05) :1800-1805
[5]   Cytomegalovirus in hematopoietic stem cell transplant recipients: Current status, known challenges, and future strategies [J].
Boeckh, M ;
Nichols, WG ;
Papanicolaou, G ;
Rubin, R ;
Wingard, JR ;
Zaia, Y .
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2003, 9 (09) :543-558
[6]  
Boeckh M, 1996, BLOOD, V88
[7]   Valganciclovir for the Prevention of Complications of Late Cytomegalovirus Infection After Allogeneic Hematopoietic Cell Transplantation A Randomized Trial [J].
Boeckh, Michael ;
Nichols, W. Garrett ;
Chemaly, Roy F. ;
Papanicolaou, Genovefa A. ;
Wingard, John R. ;
Xie, Hu ;
Syrjala, Karen L. ;
Flowers, Mary E. D. ;
Stevens-Ayers, Terry ;
Jerome, Keith R. ;
Leisenring, Wendy .
ANNALS OF INTERNAL MEDICINE, 2015, 162 (01) :1-U132
[8]   ALLOGENEIC MARROW ENGRAFTMENT FOLLOWING WHOLE BODY IRRADIATION IN A PATIENT WITH LEUKEMIA [J].
BUCKNER, CD ;
EPSTEIN, RB ;
RUDOLPH, RH ;
CLIFT, RA ;
STORB, R ;
THOMAS, ED .
BLOOD-THE JOURNAL OF HEMATOLOGY, 1970, 35 (06) :741-&
[9]   Randomized clinical trial of ganciclovir vs acyclovir for prevention of cytomegalovirus antigenemia after allogeneic transplantation [J].
Burns, LJ ;
Miller, W ;
Kandaswamy, C ;
DeFor, TE ;
MacMillan, ML ;
van Burik, JA ;
Weisdorf, DJ .
BONE MARROW TRANSPLANTATION, 2002, 30 (12) :945-951
[10]  
Camargo Jose F, 2017, Hematol Oncol Stem Cell Ther, V10, P233, DOI 10.1016/j.hemonc.2017.05.001