The key determinants of donor lymphoid chimerism support the diagnosis of acute graft versus host disease after liver transplant and predict the clinical outcome

Abstract

Management of acute Graft versus Host Disease (aGvHD) following liver transplant (LT) is critical for reducing mortality from this life-threatening disease. The aim of this study was to examine how Donor Lymphoid Chimerism (DLC) determinants associate with the diagnosis and prediction of clinical outcome of aGvHD after LT. We retrospectively analyzed 17 LT patients (2007-2015) who were clinically suspected and DLC supportive of aGvHD. The DLC was tested by short tandem repeat with an initial 5% as positive cut off. The DLC determinants were: initial positive DLC after 30 days post-LT (InPD>30D); initial positive DLCs in whole blood, T, NK, and CD8+ cells; peak DLCs of >5% in whole blood, >50% in each of T, NK, CD8+ cells respectively; positive DLC in both CD8+ and NK cells at initial phase, DLC 50% in both CD8+ and NK cells at peak phase. Clinical outcome was determined over the following 40-day duration of treatment and/or aGvHD related motility (>40D DuT/M). Logistic regression was used to analyze >40D DuT/M in response to all the variables of DLC determinants. Of 17 aGvHD patients, the prevalence of 100% (16/16) in CD8+ cell was markedly higher than the prevalence of 41% (7/17) in whole blood, 59% (10/17), in T cell, and 38% (6/16) in NK cell at the initial detection of positive DLC. Amongst all analyzed variables of DLC determinants, InPD>30D and DLC 50% in both CD8+ and NK cells at peak phase were all significantly associated with >40D DuT/M. There was a mildly significant association with the individual variables of initial phase positive DLC in T and NK cells, and peak phase >50% DLC in T and NK cells. Regardless of initial phase or peak phase, the individual variables of DLC in whole blood and CD8+ cell had no significant relationship with >40D DuT/M (Figure 1). Initial positive DLC of CD8+ cell is a sensitive and reliable indicator supporting the diagnosis of aGvHD. Both delayed diagnosis and/or peak phase DLC over 50% in both CD8+ and NK cells strongly predicts aGvHD related negative impact following LT.Download : Download full-size image