Non-Hodgkin lymphoma after pediatric kidney transplantation

Abstract

Non-Hodgkin lymphoma (NHL) that develops after kidney transplantation belongs to post-transplant lymphoproliferative disorders (PTLD) occurring with an incidence of 2-3%. Most pediatric cases are related to primary infection with Epstein-Barr virus (EBV), able to transform and immortalize B cells and widely proliferate due to the lack of relevant control of cytotoxic T cells in patients receiving post-transplant immunosuppression. NHL may develop as a systemic disease or as a localized lesion. The clinical pattern is variable, from non-symptomatic to fulminating disease. Young age of transplant recipient, seronegative EBV status at transplantation, and EBV mismatch between donor and recipient (D+/R-) are regarded as risk factors. Immunosuppression impacts the development of both early and late NHLs. Specific surveillance protocols, including monitoring of EBV viral load, are used in patients at risk; however, detailed histopathology diagnosis and evaluation of malignancy staging is crucial for therapeutic decisions. Minimizing of immunosuppression is a primary management, followed by the use of rituximab in B-cell NHLs. Specific chemotherapeutic protocols, adjusted to lymphoma classification and staging, are used in advanced NHLs. Radiotherapy and/or surgical removal of malignant lesions is limited to the most severe cases. Outcome is variable, depending on risk factors and timing of diagnosis, however is positive in pediatric patients in terms of graft function and patient survival. Kidney re-transplantation is possible in survivors who lost the primary graft due to chronic rejection, however may be performed after at least 2-3 years of waiting time, careful verification of malignancy-free status, and gaining immunity against EBV.

Keywords: Kidney transplantation; Management; Non-Hodgkin lymphoma (NHL); Risk factors.

Fig. 1.

Management of PTLD/NHL in patients after pediatric kidney transplantation at risk (adapted from [13, 35, 38, 43, 53, 66]). EBV, Epstein-Barr virus; NHL, non-Hodgkin lymphoma; MMF, mycophenolate mofetil; AZA, azathioprine; CNI, calcineurin inhibitor; USG, ultrasonography; CT, computed tomography; MRI, magnetic resonance imaging; PET-CT, positron emission tomography/computed tomography; EBER, EBV-encoded RNA hybridization