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.

Risk of subsequent primary lymphoma in a cohort of 69,460 five‐year survivors of childhood and adolescent cancer in Europe: The PanCareSurFup study

“… 35 , 36 Among (bilateral) Wilms tumor survivors, the increased risk may to some extent also be related to immunosuppressive therapy for a kidney transplant, which could cause posttransplantation lymphoproliferative disorders, 37 including NHL, although typically this occurs in the first few years after kidney transplantation, with a potential second peak 7–10 years later. 38 However, in our data, all Wilms tumor survivors who developed NHL had unilateral Wilms tumor; and, for 9 of 10 Wilms tumor survivors who developed NHL, this occurred at least 13 years after the original Wilms tumor diagnosis (range, 6–53 years), suggesting that this is probably an unlikely explanation. Similarly, stem cell transplantation among leukemia survivors may have increased the risk of posttransplantation lymphoproliferative disorders, including NHL; but, in our cohort, only one leukemia survivor with NHL had undergone stem cell transplantation.…”

“…Exposure to prolonged chemotherapy has been shown to be immunosuppressive and thus may create an environment in which latent oncogenic viruses, such as Epstein–Barr virus, that have been associated with NHL development may be reactivated 35,36 . Among (bilateral) Wilms tumor survivors, the increased risk may to some extent also be related to immunosuppressive therapy for a kidney transplant, which could cause posttransplantation lymphoproliferative disorders, 37 including NHL, although typically this occurs in the first few years after kidney transplantation, with a potential second peak 7–10 years later 38 . However, in our data, all Wilms tumor survivors who developed NHL had unilateral Wilms tumor; and, for 9 of 10 Wilms tumor survivors who developed NHL, this occurred at least 13 years after the original Wilms tumor diagnosis (range, 6–53 years), suggesting that this is probably an unlikely explanation.…”

“…35,36 Among (bilateral) Wilms tumor survivors, the increased risk may to some extent also be related to immunosuppressive therapy for a kidney transplant, which could cause posttransplantation lymphoproliferative disorders, 37 including NHL, although typically this occurs in the first few years after kidney transplantation, with a potential second peak 7-10 years later. 38 sarcoma are also at risk; it would be important for health care professionals responsible for the long-term follow-up of these survivors to be aware of the increased risk. Finally, it may be worth emphasizing to survivors that treatment with radiotherapy does not seem to suggest an increased risk of SPLs.…”