Abstract
EBV-associated post-transplant lymphoproliferative disease (PTLD) following Alemtuzumab-based allo-SCT is a relatively uncommon and challenging clinical problem but has not received detailed study in a large cohort. Quantitative-PCR (qPCR) monitoring for EBV reactivation post allo-SCT is now commonplace but its diagnostic and predictive value remains unclear. Sixty-nine patients with PTLD following Alemtuzumab-based allo-SCT were studied. Marked clinicopathological heterogeneity was evident; lymphadenopathy was frequently absent, whereas advanced extranodal disease was common. The median viral load at clinical presentation was 49 300 copies/mL (50–65 200 000 copies/mL) and, notably, 23% and 45% of cases, respectively, had ⩽10 000 and ⩽40 000 copies/mL. The overall response rate to rituximab as first-line therapy was 70%. For rituximab failures, chemotherapy was ineffectual but DLIs were successful. A four-parameter prognostic index predicted response to therapy (OR 0.30 (0.12–0.74); P=0.009] and PTLD mortality (hazard ratio (HR) 1.81 (1.12–2.93) P=0.02) on multivariate analysis. This is the largest detailed series of EBV-associated PTLD after allo-SCT. At clinical presentation, EBV-qPCR values are frequently below customary thresholds for pre-emptive therapy, challenging current paradigms for monitoring and intervention. A four-point score identifies a proportion of patients at risk of rituximab-refractory disease for whom alternative therapy is needed.
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CPF received research funding from Leukaemia and Lymphoma Research, UK. DB received research funding from the Wellcome Trust UK.
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CPF has received travel grants and speaker honoraria from Roche UK. ARP has received travel grants, advisory board and speaker honoraria from Roche UK. SC has received travel grants from Roche UK.
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Fox, C., Burns, D., Parker, A. et al. EBV-associated post-transplant lymphoproliferative disorder following in vivo T-cell-depleted allogeneic transplantation: clinical features, viral load correlates and prognostic factors in the rituximab era. Bone Marrow Transplant 49, 280–286 (2014). https://doi.org/10.1038/bmt.2013.170
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DOI: https://doi.org/10.1038/bmt.2013.170
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