Greatly reduced risk of EBV reactivation in rituximab-experienced recipients of alemtuzumab-conditioned allogeneic HSCT

• Published in: Bone marrow transplantation (Basingstoke) Vol. 51; no. 6; pp. 825 - 832
• Main Authors: Burns, D M, Rana, S, Martin, E, Nagra, S, Ward, J, Osman, H, Bell, A I, Moss, P, Russell, N H, Craddock, C F, Fox, C P, Chaganti, S
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.06.2016; Nature Publishing Group
• Subjects: 631/250/1904; 631/250/255; 631/67/1990; Adolescent; Adult; Aged; Alemtuzumab; Alemtuzumab - adverse effects; Alemtuzumab - therapeutic use; Bone marrow; Cell Biology; Dosage and administration; Epstein-Barr virus; Female; Health aspects; Hematology; Hematopoietic stem cell transplantation; Hematopoietic Stem Cell Transplantation - adverse effects; Herpesvirus 4, Human - physiology; Humans; Internal Medicine; Lymphoproliferative Disorders - etiology; Lymphoproliferative Disorders - prevention & control; Lymphoproliferative Disorders - virology; Male; Medicine; Medicine & Public Health; Methods; Middle Aged; Original; original-article; Patient outcomes; Preoperative care; Public Health; Recurrence (Disease); Retrospective Studies; Risk Assessment; Risk factors; Rituximab; Rituximab - administration & dosage; Stem cell transplantation; Stem Cells; Virus Activation - drug effects; Young Adult
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/bmt.2016.19

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.