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RECONSTITUTION OF CMV-SPECIFIC CD8+ T-CELLS FOLLOWING ALLOGENEIC STEM CELL TRANSPLANTATION (SCT): EVALUATION OF TETRAMERS FOR PREDICTION OF RECURRENT CMV REACTIVATION.
Jan W. Gratama, MD, PhD, Rik A. Brooimans, PhD, Bob L
wenberg, MD, PhD, Linda A. Sullivan, PhD, Gail H. Gasior, BA, Christopher S. Boyce, BS, Paula C. Southwick, PhD and Jan J. Cornelissen, MD, PhD. Rotterdam Netherlands, Erasmus MC, Hematology; Rotterdam Netherlands, Erasmus MC, Medical Oncology and San Diego CA, USA, Beckman Coulter, 92121, Clinical Research.
This prospective study monitored CMV-specific CD8+ T-cell recovery weekly in 31 allogeneic SCT recipients for up to 664 days 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: A*0101 VTEHDTLLY; pp65: A*0101 YSEHPTFTSQY, A*0201 NLVPMVATV, A*2402 QYDPVAALF, B*0702 TPRVTGGGAM, B*3501 IPSINVHHY; pp150: A*0301 TVYPPSSTAK; IE-1: A*0201 VLEETSVML, B*0801 ELRRKMMYM. Moderate-to-bright staining and clearly detectable proportions of tetramer-binding cells were observed for all tetramers with the exception of A*0201 VLE and A*2402 QYD (dim staining) and A*0301 TVY (no staining). Patients unable to mount a CMV-specific response above 2 cells/μL in the first 60 days post transplant were at greater risk for complications than those who were able to do so. Patients with a response < 2 cells/μl were 6 times more likely to have recurrent viremia, and 1.7 times more likely to develop CMV disease. Of interest, this patient group was also 5 times more likely to develop extensive cGVHD, 6 times more likely to develop non-relapse fatal complications, and 9 times more likely to develop at least one of these four outcomes (p = 0.001). Tetramers have potential clinical utility in monitoring CMV-specific T-cells post SCT to predict patients at risk of CMV-related complications.