Management of posttransplant lymphoproliferative disorders following solid organ transplant: an update

Abstract

Development of secondary malignancies is a well-known complication of solid organ transplant, with skin cancer and lymphoproliferative disorders being most frequently observed. Posttransplant lymphoproliferative disorders, caused by diminished immune surveillance, represent a broad spectrum of pathological and clinical disorders, ranging from benign conditions to very aggressive lymphomas. Here we review treatment options for adult patients experiencing posttransplant lymphoproliferative disorders following solid organ transplant.

Posttransplant Lymphoproliferative Disorders Following Kidney Transplantation

“…123 Most experience however has been obtained with rituximab, a chimeric murine/human anti-CD20 antibody, with numerous case reports, case series and larger retrospective analyses found in the international literature. 122 Besides five prospective trials have been published till now assessing the role of rituximab in PTLD, showing overall response rates ranging between 44% and 64%. [124][125][126][127][128] Most patients were treated with the standard rituximab dose of 375 mg/m²/week during 4 consecutive weeks, although Gonzalez-Barca et al introduced the concept of risk adapted extended treatment with rituximab in case of partial response following 4 weekly admissions.…”

“…121 In adults all currently available evidence regarding the use of chemotherapy is based on retrospective data. 122 In an analysis of the Israel Penn International Transplant Tumor Registry outcome with different chemotherapy schedules were compared. Treatment with CHOP chemotherapy was associated with a 5 year overall survival of 24% with a PTLD-specific mortality of 34%, whereas single agent chemotherapy appeared to be inferior compared to combination chemotherapy.…”

Untitled

“…3 However, the reduction of immunosuppression is followed by complete remission only in localized and histologically less aggressive forms, with most cases requiring addition of a chemotherapy regimen (rituximab and/or cyclophosphamide, doxorubicin, vincristine, prednisone + rituximab). 4 On the other hand, although an imTOR has an antiproliferative effect, 5 its use is not free from possible secondary effects.…”

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] Several risk factors for its development have been described, with infection by Epstein-Barr virus being a main cause of early-onset forms and chronic antigen stimulation of donors and/or accumulated immunosuppression as factors of later forms of lymphocyte transformation. 2 In the literature as a first-line treatment after PTLD diagnosis, in addition to specific treatments (chemoradiation, radiotherapy, and/or immunotherapy), it is recommended that either doses of calcineurin inhibitors be decreased or agent converted to inhibitors of mammalian target of rapamycin (imTOR), 10 since, with either, the reduction of immunosuppression would restore the ability of the receptor's immune system to control the uncontrolled proliferation of lymphomatous cells.…”

“…3 However, the reduction of immunosuppression is followed by complete remission only in localized and histologically less aggressive forms, with most cases requiring addition of a chemotherapy regimen (rituximab and/or cyclophosphamide, doxorubicin, vincristine, prednisone + rituximab). 4 On the other hand, although an imTOR has an antiproliferative effect, 5 its use is not free from possible secondary effects.Here, we present a patient diagnosed with PTLD 3 years after renal transplant who developed a potentially lethal complication related to conversion to imTOR. Because clinical studies that have established the most suitable treatment are lacking, it is recommended to identify a strategy, defining possible risks versus benefits of the conversion to imTOR in cases of PTLD, and to maintain a high level of surveillance in case of possible secondary effects, which can be verified after their introduction.…”