EBV-associated post-transplant lymphoproliferative disorder following in vivo T-cell-depleted allogeneic transplantation: clinical features, viral load correlates and …

CP Fox, D Burns, AN Parker, KS Peggs… - Bone marrow …, 2014 - nature.com
CP Fox, D Burns, AN Parker, KS Peggs, CM Harvey, S Natarajan, DI Marks, B Jackson…
Bone marrow transplantation, 2014nature.com
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 …
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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