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Immune monitoring with iTAg™ MHC tetramers for prediction of recurrent or persistent cytomegalovirus (CMV) infection in allogeneic stem cell transplant (SCT) recipients: A prospective multicenter clinical trial

Year: 2006

Type: article

Abstract: Background: CMV infection is an important cause of morbidity and mortality in SCT recipients despite the introduction of routine post-transplant virologic monitoring and the use of potent antiviral agents. This prospective multicenter study evaluated the use of tetramers in monitoring CMV-specific T cell recovery following allogeneic SCT to predict patients at risk for CMV-related complications. Methods: Patients were tested every 2 weeks and monitored for up to 1 year post-transplant. iTAg™ MHC Tetramers (Beckman Coulter, San Diego) were used to enumerate CMV-specific CD8+ T cells by flow cytometry using a single-platform absolute counting method. The following tetramers were included: pp50: A0101 VTEHDTLLY; pp65: A0201 NLVPMVATV, B0702 TPRVTGGGAM, B3501 IPSINVHHY; IE-1: B0801 ELRRKMMYM. All patients underwent weekly surveillance by pp65 antigenemia or DNAemia with preemptive antiviral therapy. Results: Data were analyzed for 83 CMV-seropositive recipients with 3 or more tetramer values. Median follow-up was 9 months (range 2–12). Delayed recovery of CMV-specific CD8+ T cells (<7 cells/mL in all blood samples during the first 65 days post-transplant) predisposes patients to CMV-related complications (Table 1). These patients are 2.6 times more likely to develop recurrent or persistent CMV infection, 4.8 times more likely to develop CMV disease, 2.4 times more likely to develop fatal complications, and 2.2 times more likely to develop one of more of these outcomes than patients showing rapid recovery. Rapid recovery (≥7 cells/mL in any blood sample during the first 65 days post-transplant) was associated with protection from CMV-related complications. Inter- and intraassay variability of the assay was ≤8% and ≤8%, and results were available in 3 hours. Conclusions: CMV tetramer-based immune monitoring, in conjunction with virologic monitoring, can be an important new tool that permits clinicians to assess the period of risk of CMV-related complications and to make appropriate preemptive therapeutic choices in managing allogeneic SCT patients. For high-risk patients with delayed immunologic recovery, virologic monitoring, CMV tetramer monitoring, and other preemptive strategies should be continued beyond 100 days post-transplant. For low-risk patients (≥7 tetramer-positive cells/mL), studies are needed to determine how long virologic monitoring should be continued or if preemptive therapy may be modified or instituted at higher viral load levels (Table 1).Table 1Relative RiskRecurrent or Persistent CMV InfectionCMV DiseaseTransplant-Related MortalityComposite (one or More of These Outcomes)Delayed recovery of CMV-specific CD8+ cells (< 7 cells/uL)2.64.82.42.2P = .02P = .09P = .12P = .01 Open table in a new tab

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2005.11.248