Risk Factors for the Incidence of and the Mortality due to Post-Transplant Lymphoproliferative Disorder after Hematopoietic Cell Transplantation

Abstract

Post-transplant lymphoproliferative disorder (PTLD) is a potentially serious complication that occurs following hematopoietic cell transplantation (HCT), in which B cells transformed by Epstein-Barr virus (EBV) proliferate uncontrollably. It is unknown whether risk factors for the incidence of PTLD are identical to those for mortality due to PTLD, a clinically more important outcome. We sought to determine the risk factors influencing the incidence of PTLD and those influencing mortality due to PTLD in a cohort of 1184allogenic HCT recipients. All patients were predisposed to PTLD, because their graft-versus-host disease (GVHD) prophylaxis included antithymocyte globulin. The overall PTLD incidence was 9.0%, and mortality due to PTLD was1.1%. Inmultivariate analysis, risk factors for PTLD incidence include donor+/recipient- (D+/R-) EBVserostatus (subhazard ratio [SHR], 3.3; P=.002), use of a donor other than an HLA-matched sibling donor (non-MSD) (SHR, 1.7; P=.029), receipt of total body irradiation (TBI; SHR, 3.3; P=.008), and the absence of GVHD (SHR, 3.3; P < .001). The sole risk factor for mortality due to PTLD among all patients was D+/R- serostatus (SHR, 5.8; P=.022). Risk factors for mortality due to PTLD among patients who developed PTLD were use of a bone marrow (BM) graft (compared with peripheral blood stem cells [PBSCs]; SHR, 22.8; P < .001) and extralymphatic involvement (SHR, 14.6; P < .001). Interestingly, whereas the absence of GVHD was a risk factor for PTLD incidence, there was a trend toward the presence of GVHD as a risk factor for PTLD mortality (SHR, 4.2; P=.093). Likewise, whereas use of a BM graft was a risk factor for PTLD mortality, there was a trend toward use of a PBSC graft as a risk factor for PTLD incidence (SHR, 0.44; P=.179). Some risk factors for the incidence of PTLD are identical to the risk factors for mortality due to PTLD (ie, D+/R- serostatus), whereas other risk factors are disparate. Specifically, TBI was identified as a risk factor for PTLD incidence but not for PTLD mortality; the absence of GVHD was a risk factor for PTLD incidence, whereas the presence of GVHD was possibly a risk factor for PTLD mortality; and receipt of a PBSC graft was possibly a risk factor for PTLD incidence, whereas receipt of a BM graft was a risk factor for PTLD mortality.