Early CMV Viremia Is Associated with Impaired Viral Control following Nonmyeloablative Hematopoietic Cell Transplantation with a Total Lymphoid Irradiation and Antithymocyte Globulin Preparative Regimen

被引:19
作者
Schaenman, Joanna M. [1 ]
Shashidhar, Sumana [2 ]
Rhee, Chanu [3 ]
Wong, Jonathan [1 ]
Navato, Shelly [2 ]
Wong, Ruby M. [4 ]
Ho, Dora Y. [1 ]
Arai, Sally [2 ]
Johnston, Laura [2 ]
Brown, Janice M. [1 ,2 ]
机构
[1] Stanford Univ, Div Infect Dis, Med Ctr, Stanford, CA 94305 USA
[2] Stanford Univ, Div Blood & Marrow Transplantat, Med Ctr, Stanford, CA 94305 USA
[3] Stanford Univ, Dept Med, Med Ctr, Stanford, CA 94305 USA
[4] Stanford Univ, Dept Hlth Res & Policy, Med Ctr, Stanford, CA 94305 USA
基金
美国国家卫生研究院;
关键词
Cytomegalovirus; Bone marrow transplantation; Nonmyeloablative; Immune reconstitution; Antithymocyte globulin; CYTOMEGALOVIRUS-SPECIFIC CD4(+); VERSUS-HOST-DISEASE; IMMUNE RECONSTITUTION; REDUCED-INTENSITY; REACTIVATION; GANCICLOVIR; INFECTIONS; RECIPIENTS; ALEMTUZUMAB; ANTIGENEMIA;
D O I
10.1016/j.bbmt.2010.08.010
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The reconstitution of immune function after hematopoietic cell transplant (HCT) plays an important role in the control of viral infections. Both donor and recipient cytomegalovirus (CMV) serostatus has been shown to contribute to effective immune function; however, the influence of a nonmyeloablative preparative (NMA) regimen using total lymphoid irradiation (TLI) and antithymocyte globulin (ATG) on antiviral immune reconstitution has not yet been described. In 117 recipients of NMA HCT patients following ATG and TLI, not unexpectedly, CMV viremia was seen in approximately 60% of the seropositive patients regardless of donor serostatus, and recipient seropositivity significantly increased the odds of CMV viremia after transplant in a multivariate analysis. The administration of ATG and TLI resulted in a strikingly earlier viremia in the post-transplant period when compared to the previously reported timing of viremia following myeloablative preparative regimens, especially for transplant recipients who were seropositive for CMV with seronegative donors. Furthermore, early viremia in the setting of a CMV naive donor was associated with a delay in functional antiviral control. These observations demonstrate the dynamic nature of immunity in relation to CMV antigen exposure in the complex environment resulting from NMA conditions where both donor and residual recipient immune response affect viral control. Biol Blood Marrow Transplant 17: 693-702 (2011) (C) 2011 American Society for Blood and Marrow Transplantation
引用
收藏
页码:693 / 702
页数:10
相关论文
共 24 条
[1]   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
[2]   Cytomegalovirus pp65 antigenemia-guided early treatment with ganciclovir versus ganciclovir at engraftment after allogeneic marrow transplantation: A randomized double-blind study [J].
Boeckh, M ;
Gooley, TA ;
Myerson, D ;
Cunningham, T ;
Schoch, G ;
Bowden, RA .
BLOOD, 1996, 88 (10) :4063-4071
[3]   High incidence of cytomegalovirus infection after nonmyeloablative stem cell transplantation: potential role of Campath-1H in delaying immune reconstitution [J].
Chakrabarti, S ;
Mackinnon, S ;
Chopra, R ;
Kottaridis, PD ;
Peggs, K ;
O'Gorman, P ;
Chakraverty, R ;
Marshall, T ;
Osman, H ;
Mahendra, P ;
Craddock, C ;
Waldmann, H ;
Hale, G ;
Fegan, CD ;
Yong, K ;
Goldstone, AH ;
Linch, DC ;
Milligan, DW .
BLOOD, 2002, 99 (12) :4357-4363
[4]   Direct visualization of cytomegalovirus-specific T-cell reconstitution after allogeneic stem cell transplantation [J].
Cwynarski, K ;
Ainsworth, J ;
Cobbold, M ;
Wagner, S ;
Mahendra, P ;
Apperley, J ;
Goldman, J ;
Craddock, C ;
Moss, PAH .
BLOOD, 2001, 97 (05) :1232-1240
[5]   CMV-specific T cell therapy [J].
Einsele, Hennann ;
Kapp, Markus ;
Grigoleit, Goetz Ulrich .
BLOOD CELLS MOLECULES AND DISEASES, 2008, 40 (01) :71-75
[6]   Cytomegalovirus-specific CD4+ and CD8+ T-cells follow a similar reconstitution pattern after allogeneic stem cell transplantation [J].
Foster, AE ;
Gottlieb, DJ ;
Sartor, M ;
Hertzberg, MS ;
Bradstock, KF .
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2002, 8 (09) :501-511
[7]   Immune reconstitution to cytomegalovirus after allogeneic hematopoietic stem cell transplantation: impact of host factors, drug therapy, and subclinical reactivation [J].
Hakki, M ;
Riddell, SR ;
Storek, J ;
Carter, RA ;
Stevens-Ayers, T ;
Sudour, P ;
White, K ;
Corey, L ;
Boeckh, M .
BLOOD, 2003, 102 (08) :3060-3067
[8]   Immunological response to cytomegalovirus in congenitally infected neonates [J].
Hassan, J. ;
Dooley, S. ;
Hall, W. .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2007, 147 (03) :465-471
[9]   Subcutaneous alemtuzumab vs ATG in adjusted conditioning for allogeneic transplantation:: influence of Campath dose on lymphoid recovery, mixed chimerism and survival [J].
Juliusson, G ;
Theorin, N ;
Karlsson, K ;
Frödin, U ;
Malm, C .
BONE MARROW TRANSPLANTATION, 2006, 37 (05) :503-510
[10]   Incidence and outcome of cytomegalovirus infections following nonmyeloablative compared with myeloablative allogeneic stem cell transplantation, a matched control study [J].
Junghanss, C ;
Boeckh, M ;
Carter, RA ;
Sandmaier, BM ;
Maris, MB ;
Maloney, DG ;
Chauncey, T ;
McSweeney, PA ;
Little, MT ;
Corey, L ;
Storb, R .
BLOOD, 2002, 99 (06) :1978-1985