Matched-pair analysis: identification of factors with independent influence on the development of PTLD after kidney or liver transplantation.

Lisa Rausch,Lars Pape,Nikos Emmanouilidis,Christian Koenecke,Hans-Friedrich Koch,Ulrich Baumann,Harald Schrem,Viktor Arelin,Alexander Kaltenborn,Frank Lehner

doi:10.1186/s13737-016-0036-1

Abstract

BackgroundPost-transplant lymphoproliferative disorder (PTLD) adversely affects patients’ long-term outcome.MethodsThe paired t test and McNemar’s test were applied in a retrospective 1:1 matched-pair analysis including 36 patients with PTLD and 36 patients without PTLD after kidney or liver transplantation. Matching criteria were age, gender, indication, type of transplantation, and duration of follow-up. All investigated PTLD specimen were histologically positive for EBV. Risk-adjusted multivariable regression analysis was used to identify independence of risk factors for PTLD detected in matched-pair analysis. The resultant prognostic model was assessed with ROC-curve analysis.ResultsPatients suffering with PTLD had shorter mean survival (p = 0.004), more episodes of CMV infections or reactivations (p = 0.042), and fewer recipient HLA A2 haplotypes (p = 0.007), a tacrolimus-based immunosuppressive regimen (p = 0.052) and higher dosages of tacrolimus at hospital discharge (Tac dosage) (p = 0.052). Significant independent risk factors for PTLD were recipient HLA A2 (OR = 0.07, 95 % CI = 0.01–0.55, p = 0.011), higher Tac dosages (OR = 1.29, 95 % CI = 1.01–1.64, p = 0.040), and higher numbers of graft rejection episodes (OR = 0.38, 95 % CI = 0.17–0.87, p = 0.023). The following prognostic model for the prediction of PTLD demonstrated good model fit and a large area under the ROC curve (0.823): PTLD probability in % = Exp(y)/(1 + Exp(y)) with y = 0.671 − 1.096 × HLA A2-positive recipient + 0.151 × Tac dosage − 0.805 × number of graft rejection episodes.ConclusionsThis study suggests prognostic relevance for recipient HLA A2, CMV, and EBV infections or reactivations and strong initial tacrolimus-based immunosuppression. Patients with risk factors may benefit from intensified screening for PTLD.

Highlights

Post-transplant lymphoproliferative disorder (PTLD) adversely affects patients’ long-term outcome
Definition of analyzed variables Concerning donor and recipient Human leukocyte antigen (HLA) status, we only considered the donors’ HLA of the actual transplanted organ at PTLD diagnosis, which may be relevant in cases with multiple transplants during follow-up (n = 5)
The underlying diseases leading to transplantation form a heterogeneous group of diseases, varying between different types of glomerulonephritis to kidney dysplasia, autosomal dominant polycystic disease, hemolytic-uremic syndrome, and others

Summary

Introduction

Post-transplant lymphoproliferative disorder (PTLD) adversely affects patients’ long-term outcome. Post-transplant lymphoproliferative disorders (PTLD) are a heterogeneous group of diseases [1]. The underlying disease leading to transplantation might have an influence on the risk of developing PTLD [5]. B5, HLA-B18, HLA-B21, and HLA-B35 in transplant recipients as well as HLA-B40 group in EBV-seropositive and HLA-B8 in EBV-seronegative patients were described to be associated with an increased risk for PTLD, whereas HLA-A3 and HLA-DR7 appear to decrease the risk [11,12,13]. Beside the recipients’ HLA status, the donors’ HLA typing result as well as the matching or mismatching of both seems to have an influence on the development of PTLD [1, 4, 14,15,16]

Objectives

Methods

Results

Discussion

Conclusion