Cytomegalovirus (CMV) infections and CMV-specific cellular immune reconstitution following reduced intensity conditioning allogeneic stem cell transplantation with Alemtuzumab.
We studied the incidence and recurrence of Cytomegalovirus (CMV) infection and reactivation in 38 recipients of Alemtuzumab reduced intensity conditioning-stem cell transplantation, and used CMV-HLA tetramer studies to discover if these events correlated with recovery of circulating CMV-specific CD8+ T cells (cytotoxic T lymphocyte (CTLs)). The cumulative incidence of CMV infection was 60% at 1 year (95% CI, 45-78%) with a median reactivation time of 24 days (range 5-95 days). All patients with CMV reactivation received Ganciclovir or Foscarnet, and only one developed CMV disease. More strikingly, only 8/21 patients had relapse of CMV antigenemia. Tetramer analysis in 13 patients showed that 11 reconstituted CMV CTLs (7/11 by day 30 and 10/11 by day 90). The development of CMV infection was accompanied by a >5-fold rise of CMV CTLs. Recurrence of CMV infection occurred only in the patients who failed to generate a CTL response to the virus. Hence, recipients of SCT using Alemtuzumab-RIC are initially profoundly immunosuppressed and have a high incidence of early CMV reactivation. However, in the majority of patients, infection is transient, and antiviral T cell reconstitution is rapid. Monitoring with CMV-specific CTLs may help identify the subset of patients at risk from recurrent infection or disease.
Lamba
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R
Department of Medicine, Baylor College of Medicine and The Methodist Hospital, Houston, TX 77030, USA. rlamba@tmh.tmc.edu
Carrum
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Myers
G D
GD
Bollard
C M
CM
Krance
R A
RA
Heslop
H E
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Brenner
M K
MK
Popat
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D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage*; D000956:Antigens, Viral / Q000097:blood; D003586:Cytomegalovirus Infections / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000517:prevention & control / Q000821:virology; D019337:Hematologic Neoplasms / Q000097:blood / Q000150:complications / Q000276:immunology / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020127:Recovery of Function / Q000187:drug effects / Q000276:immunology*; D033581:Stem Cell Transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous; D014775:Virus Activation / Q000187:drug effects / Q000276:immunology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000956:Antigens, Viral; D000074323:Alemtuzumab