BACKGROUND: Epstein-Barr virus (EBV) reactivation is a frequent event after allogeneic stem cell transplantation and may progress to life-threatening lymphoproliferative disease (EBV-LPD) in the absence of adequate EBV-specific T cell immunity. Quantification of EBV DNA load in asymptomatic individuals who are at risk is a useful (although not entirely predictive) indicator of progression to EBV-LPD and guide for preemptive treatment with CD20 antibodies. METHODS: With the aim of improving the identification of patients at risk, we retrospectively analyzed, within a cohort of 25 consecutive allogeneic stem cell transplant recipients at risk for EBV-LPD, the pattern of T cell reconstitution during EBV reactivation in all preemptively treated patients (8 patients). RESULTS: In 6 of 8 cases, a significant T cell reconstitution (i.e., a CD3+ T cell count of >300 cells/microL) was documented during EBV reactivation, which included an expansion of EBV-specific memory T cells, as shown by human leukocyte antigen class I tetramer analysis. Additional evidence for the antiviral potential of this T cell reconstitution was obtained prospectively from a cohort of 14 consecutive allogeneic stem cell transplant recipients at risk for EBV-LPD. EBV reactivation occurred in 3 patients. Preemptive treatment was successfully withheld for 2 of these patients in light of concurrent (EBV-specific) T cell recovery. CONCLUSION: We conclude that analysis of the level of (EBV-specific) T cell reconstitution during EBV reactivation is an important second parameter, in addition to quantification of EBV DNA load, that will be instrumental in a more accurate definition of patients at risk for EBV-LPD who, given their immunoincompetence, will be most certainly dependent on preemptive interventions.
BACKGROUND: Epstein-Barr virus (EBV) reactivation is a frequent event after allogeneic stem cell transplantation and may progress to life-threatening lymphoproliferative disease (EBV-LPD) in the absence of adequate EBV-specific T cell immunity. Quantification of EBV DNA load in asymptomatic individuals who are at risk is a useful (although not entirely predictive) indicator of progression to EBV-LPD and guide for preemptive treatment with CD20 antibodies. METHODS: With the aim of improving the identification of patients at risk, we retrospectively analyzed, within a cohort of 25 consecutive allogeneic stem cell transplant recipients at risk for EBV-LPD, the pattern of T cell reconstitution during EBV reactivation in all preemptively treated patients (8 patients). RESULTS: In 6 of 8 cases, a significant T cell reconstitution (i.e., a CD3+ T cell count of >300 cells/microL) was documented during EBV reactivation, which included an expansion of EBV-specific memory T cells, as shown by human leukocyte antigen class I tetramer analysis. Additional evidence for the antiviral potential of this T cell reconstitution was obtained prospectively from a cohort of 14 consecutive allogeneic stem cell transplant recipients at risk for EBV-LPD. EBV reactivation occurred in 3 patients. Preemptive treatment was successfully withheld for 2 of these patients in light of concurrent (EBV-specific) T cell recovery. CONCLUSION: We conclude that analysis of the level of (EBV-specific) T cell reconstitution during EBV reactivation is an important second parameter, in addition to quantification of EBV DNA load, that will be instrumental in a more accurate definition of patients at risk for EBV-LPD who, given their immunoincompetence, will be most certainly dependent on preemptive interventions.
Authors: Helen L Wu; Whitney C Weber; Christine Shriver-Munsch; Tonya Swanson; Mina Northrup; Heidi Price; Kimberly Armantrout; Mitchell Robertson-LeVay; Jason S Reed; Katherine B Bateman; Eisa Mahyari; Archana Thomas; Stephanie L Junell; Theodore R Hobbs; Lauren D Martin; Rhonda MacAllister; Benjamin N Bimber; Mark K Slifka; Alfred W Legasse; Cassandra Moats; Michael K Axthelm; Jeremy Smedley; Anne D Lewis; Lois Colgin; Gabrielle Meyers; Richard T Maziarz; Benjamin J Burwitz; Jeffrey J Stanton; Jonah B Sacha Journal: Xenotransplantation Date: 2020-01-13 Impact factor: 3.907
Authors: Deirdre O'Mahony; John C Morris; Maryalice Stetler-Stevenson; Helen Matthews; Margaret R Brown; Thomas Fleisher; Stefania Pittaluga; Mark Raffeld; Paul S Albert; Dirk Reitsma; Karen Kaucic; Luz Hammershaimb; Thomas A Waldmann; John E Janik Journal: Clin Cancer Res Date: 2009-03-17 Impact factor: 12.531
Authors: David M Burns; Rose Tierney; Claire Shannon-Lowe; Jo Croudace; Charlotte Inman; Ben Abbotts; Sandeep Nagra; Christopher P Fox; Sridhar Chaganti; Charles F Craddock; Paul Moss; Alan B Rickinson; Martin Rowe; Andrew I Bell Journal: Blood Date: 2015-10-08 Impact factor: 25.476