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35.8.4. Post-transplant lymphoproliferative disorder

Chapter 35

Post-transplant lymphoproliferative disorder (PTLD) can be a serious complication of solid organ transplantation and haematopoietic stem cell transplantation. It comprises a spectrum of B-cell hyperproliferative states ranging from benign lymphoid hyperplasia to malignant neoplasms (mostly NHL) [822]. Epstein-Barr virus (EBV) is present in the majority of PTLD tumours and plays a crucial role in the pathogenesis of these tumours. Whilst most PTLD patients have detectable EBV DNA in peripheral blood, this is a non-specific finding [823]. Therefore, there is a need for additional markers to identify transplant patients at risk of PTLD.

Engels et al. [822] studied the value of sFLCs to predict risk of PTLD in solid organ transplant patients. Pre-diagnostic serum samples were available (on average 3.5 months prior to diagnosis) from 29 transplant recipients with PTLD and 57 matched controls. A polyclonal sFLC elevation was found in a higher proportion of cases compared with controls (59% vs 37%), and was significantly associated with increased risk of early-onset and polymorphic PTLD. A stronger relationship between sFLCs and PTLD was observed among non-kidney transplant recipients. A subsequent study of PTLD in renal transplant patients found no association of elevated sFLC concentrations with PTLD risk [824]. This suggests that non-specific increases in sFLCs due to renal insufficiency (Section 6.3) reduce the utility of such rises for predicting PTLD.

In a second study by Engels and colleagues [825], plasma FLC concentrations from 36 paediatric transplant recipients were measured (18 allogeneic, haematopoietic stem cell transplants and 18 liver transplants). Polyclonal FLC elevations were seen in 26% of the patients and monoclonal elevations in 6%; all of the latter had PTLD. It was also noted that there was a tendency for FLC concentrations to change in parallel with measurements of EBV load. Monoclonal immunoglobulins were present in over 90% of the plasma samples but these did not always match the light chain clonality indicated by FLC ratios. The authors suggested this was because PTLD is an oligoclonal disorder rather than a truly monoclonal one. In a more recent, third report from Engels et al. [826], 43 allogeneic haematopoietic stem cell transplant recipients were enrolled and 11 with PTLD were compared with 32 without PTLD. Of the 11 patients with PTLD, only three had elevated FLC concentrations and none had abnormal ratios and there were more frequent FLC abnormalities amongst the controls, indicating that FLC concentrations were not associated with the risk of developing PTLD. In both cases and controls, elevations of κ FLC were more frequent than λ. However, the authors considered that the timing of their serum collection, soon after transplant, may have compromised the identification of PTLD (which tends to arise later) and concluded that further investigations were warrented to understand the biological implications of FLC abnormalities in transplant recipients.