Abstract
EBV-associated post-transplant lymphoproliferative disease (PTLD) remains an important complication of allogeneic haematopoietic stem cell transplantation (allo-HSCT). We retrospectively analysed the incidence and risk factors for EBV reactivation in 186 adult patients undergoing consecutive allo-HSCT with alemtuzumab T-cell depletion at a single centre. The cumulative incidence of EBV reactivation was 48% (confidence interval (CI) 41–55%) by 1 year, with an incidence of high-level EBV reactivation of 18% (CI 13–24%); 8 patients were concurrently diagnosed with PTLD. Amongst patients with high-level reactivation 31/38 (82%) developed this within only 2 weeks of first EBV qPCR positivity. In univariate analysis age⩾50 years was associated with significantly increased risk of EBV reactivation (hazard ratio (HR) 1.54, CI 1.02–2.31; P=0.039). Furthermore, a diagnosis of non-Hodgkin lymphoma (NHL) was associated with greatly reduced risk of reactivation (HR 0.10, CI 0.03–0.33; P=0.0001) and this was confirmed in multivariate testing. Importantly, rituximab therapy within 6 months prior to allo-HSCT was also highly predictive for lack of EBV reactivation (HR 0.18, CI 0.07–0.48; P=0.001) although confounding with NHL was apparent. Our data emphasise the risk of PTLD associated with alemtuzumab. Furthermore, we report the clinically important observation that rituximab, administered in the peri-transplant period, may provide effective prophylaxis for PTLD.
Highlights
Post-transplant lymphoproliferative disease (PTLD) remains a life-threatening complication of allogeneic haematopoietic stem cell transplant.[1,2,3] In this setting, almost all cases arise from donor-derived B cells, transformed by the ubiquitous doublestranded DNA gamma-herpesvirus EBV
We report clinically important rates of these complications, with 48% of individuals exhibiting EBV qPCR positivity by 1 year post transplant and 18% developing highlevel EBV reactivation
This incidence is noticeably greater than that reported in the study of 111 alemtuzumab-treated patients by Carpenter et al.,[11] in which only 0.9% of patients developed PTLD
Summary
Post-transplant lymphoproliferative disease (PTLD) remains a life-threatening complication of allogeneic haematopoietic stem cell transplant (allo-HSCT).[1,2,3] In this setting, almost all cases arise from donor-derived B cells, transformed by the ubiquitous doublestranded DNA gamma-herpesvirus EBV. Relatively few studies have examined the third generation humanised Ab Campath-1H (alemtuzumab), which has superseded the other Abs in routine clinical practice.[17] Alemtuzumab has a much longer half-life than Campath-1G (15–21 days, compared with less than 24 h) and causes prolonged delays in the reconstitution of both general[18,19] and EBV-specific T-cell immunity.[20] it might contribute to an increased risk of PTLD compared with earlier antibodies. Received 9 November 2015; revised 30 December 2015; accepted 4 January 2016; published online 22 February 2016 To explore these issues, work was undertaken to define incidence, kinetics and risk factors for EBV reactivation and PTLD amongst adult patients undergoing alemtuzumab TCD allo-HSCT at a major UK transplant centre. DNAemia, DNAemia, DNAemia, DNAemia, DNAemia, diagnosed, disease day copies/mL day copies/mL copies/mL day Outcome, cause of death
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