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Natural history of EBV replication and viral load dynamics after alemtuzumab based allogeneic stem cell transplantation.

Marzolini, MAV; Wilson, AJ; Sanchez, E; Carpenter, B; Chakraverty, R; Hough, R; Kottaridis, P; ... Peggs, KS; + view all (2021) Natural history of EBV replication and viral load dynamics after alemtuzumab based allogeneic stem cell transplantation. Transplantation and Cellular Therapy 10.1016/j.jtct.2021.04.020. (In press). Green open access

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Abstract

BACKGROUND: Epstein-Barr virus (EBV) load monitoring post-allogeneic haematopoietic stem cell transplantation (HSCT) enables earlier detection of EBV replication and is often used as a trigger for pre-emptive therapies aiming to reduce EBV-related diseases. Our institutional strategy is to treat patients with clinical signs of EBV-related disease accompanied by a rising viral load, rather than to intervene solely based on viral load. This affords an opportunity to study the natural history of EBV replication and to assess if our strategy reduces over-treatment without compromising outcomes. OBJECTIVE: Our objective was to assess the natural history of untreated EBV replication in patients who have received an alemtuzumab-based allogeneic haematopoietic stem cell transplant and to examine whether our clinical strategy reduced over-treatment without compromising patient outcomes. STUDY DESIGN: We present a retrospective, single-centre, observational study of 515 consecutive patients (≥18 years) undergoing T-cell depleted allogeneic haematopoietic stem cell transplantation incorporating alemtuzumab. Patients underwent surveillance monitoring for EBV by qPCR in the peripheral blood at least weekly up to 100 days post-transplant and longer if they remained on immunosuppressive therapy. Cumulative incidence of EBV detection and EBV-related disease were assessed. RESULTS: 192 patients had EBV DNA detectable on ≥1 occasion, with a cumulative incidence of 35.8% (31.8-40.4%), although this remained below the limit of quantification in 93 patients. Median time to first detection was 89.5 days (0-2254 days). The incidence was higher in sibling donor transplants (45.4% vs 30%, P= 0.00021) when compared to unrelated donor transplants. 20 patients developed EBV-related disease (cumulative incidence 3.9%). Two had immunosuppression reduction alone, 18 received rituximab, and 5 required additional therapies. Five patients died due to PTLD and all five had received rituximab. The positive predictive value of EBV load for disease was higher in the unrelated donor cohort but remained <75% regardless of EBV threshold (57.1-72.7%). CONCLUSIONS: The cumulative incidence of EBV-related disease in our study (3.9%) was comparable to other studies incorporating alemtuzumab and our clinical strategy reduced over-treatment in this patient population. There are limitations of PCR-based surveillance strategies as reflected in the relatively low sensitivity of the assay coupled with the low positive predictive value which may influence the potential choice of threshold for pre-emptive intervention. We conclude that it remains unclear whether treatment based on rising EBV viral load alone gives superior overall results to treatment based on the development of clinical signs of EBV-related disease in the context of a rising viral load.

Type: Article
Title: Natural history of EBV replication and viral load dynamics after alemtuzumab based allogeneic stem cell transplantation.
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.jtct.2021.04.020
Publisher version: https://doi.org/10.1016/j.jtct.2021.04.020
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Alemtuzumab, Allogeneic HSCT, EBV, PTLD (post-transplant lymphoproliferative disorder)
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > UCL Medical School
URI: https://discovery.ucl.ac.uk/id/eprint/10127678
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