Immune monitoring with iTAg MHC Tetramers for prediction of recurrent or persistent cytomegalovirus infection or disease in allogeneic hematopoietic stem cell transplant recipients: a prospective multicenter study.
Cytomegalovirus (CMV) infection is an important cause of morbidity and mortality in hematopoietic stem cell transplant recipients despite the introduction of posttransplantation viral monitoring and preemptive antiviral therapy. We evaluated the use of HLA class I tetramers in monitoring CMV-specific T-cell recovery to predict patients at risk for CMV-related complications. This prospective multicenter clinical trial obtained nearly 1400 tetramer/allele results in more than 800 biweekly blood samples from 83 patients monitored for 1 year after transplantation. Major HLA types were included (A*0101, A*0201, B*0702, B*0801, B*3501). iTAg MHC Tetramers (Beckman Coulter) were used to enumerate CMV-specific CD8(+) T cells by flow cytometry using a single-platform absolute counting method. Assay variability was 8% or less and results were available within 3 hours. Delayed recovery of CMV-specific T cells (< 7 cells/μL in all blood samples during the first 65 days after transplantation) was found to be a significant risk factor for CMV-related complications; these patients were more likely to develop recurrent or persistent CMV infection (relative risk 2.6, CI 1.2-5.8, P = .01) than patients showing rapid recovery, which was associated with protection from CMV-related complications (P = .004). CMV tetramer-based immune monitoring, in conjunction with virologic monitoring, can be an important new tool to assess risk of CMV-related complications and to guide preemptive therapeutic choices.
Department of Clinical and Tumor Immunology, Erasmus Medical Center/Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
Jan W
JW
Gratama
Michael
M
Boeckh
Ryotaro
R
Nakamura
Jan J
JJ
Cornelissen
Rik A
RA
Brooimans
John A
JA
Zaia
Stephen J
SJ
Forman
Karl
K
Gaal
Kurtis R
KR
Bray
Gail H
GH
Gasior
Christopher S
CS
Boyce
Linda A
LA
Sullivan
Paula C
PC
Southwick
D000293:Adolescent; D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000175:diagnosis / Q000209:etiology / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D015234:HLA-A Antigens / Q000235:genetics / Q000276:immunology; D015788:HLA-A1 Antigen; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology; D015793:HLA-B7 Antigen; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006650:Histocompatibility Testing; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015166:Monitoring, Immunologic / Q000379:methods*; D011183:Postoperative Complications / Q000175:diagnosis / Q000209:etiology / Q000276:immunology*; D011379:Prognosis; D011446:Prospective Studies; D015203:Reproducibility of Results; D014184:Transplantation, Homologous; D055815:Young Adult
D015234:HLA-A Antigens; C506470:HLA-A*01:01 antigen; D015788:HLA-A1 Antigen; D015235:HLA-B Antigens; C477444:HLA-B*07:02 antigen; D015793:HLA-B7 Antigen