title: Cytomegalovirus (CMV) infections and CMV-specific cellular immune reconstitution following reduced intensity conditioning allogeneic stem cell transplantation with Alemtuzumab.
abstract: 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.
authors.affiliation: Department of Medicine, Baylor College of Medicine and The Methodist Hospital, Houston, TX 77030, USA. rlamba@tmh.tmc.edu
authors.forename: R
authors.initials: R
authors.lastname: Lamba
authors.forename: G
authors.initials: G
authors.lastname: Carrum
authors.forename: G D
authors.initials: GD
authors.lastname: Myers
authors.forename: C M
authors.initials: CM
authors.lastname: Bollard
authors.forename: R A
authors.initials: RA
authors.lastname: Krance
authors.forename: H E
authors.initials: HE
authors.lastname: Heslop
authors.forename: M K
authors.initials: MK
authors.lastname: Brenner
authors.forename: U
authors.initials: U
authors.lastname: Popat
mesh_terms: 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
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000956:Antigens, Viral; D000074323:Alemtuzumab