Journal
BONE MARROW TRANSPLANTATION
Volume 49, Issue 2, Pages 280-286Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/bmt.2013.170
Keywords
alemtuzumab; DLI; EBV; immunotherapy; PTLD; SCT
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Funding
- Leukaemia and Lymphoma Research, UK
- Wellcome Trust UK
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EBV-associated post-transplant lymphoproliferative disease (3PTLD) 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 (3qPCR) 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 (350-65 200 000 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 (3OR 0.30 (30.12-0.74); P = 0.009] and PTLD mortality (3hazard ratio (3HR) 1.81 (31.12-2.93) 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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