Donor-derived post-transplant lymphoproliferative disease detection by donor-derived cell free DNA.

Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication of organ transplantation, commonly diagnosed after patients present with nonspecific constitutional symptoms and/or transplant organ dysfunction. Here we report a case of a kidney transplant recipient who was found to have highly elevated circulating donor-derived cell free DNA (dd-cfDNA) levels on routine serum surveillance for allograft rejection, initially without organ dysfunction or evidence of allograft rejection on biopsy. Later for cause imaging revealed retroperitoneal lymphadenopathy and an allograft hilar mass, which was biopsied to show post-transplant lymphoproliferative disorder/diffuse large B-cell lymphoma (DLBCL). The elevated circulating dd-cfDNA levels in this patient prompted targeted next-generation sequencing of the same 266 single-nucleotide polymorphisms used to detect dd-cfDNA on the DLBCL, which identified it as donor-derived. The patient achieved complete remission with retained allograft kidney function after reduced immunosuppression and 6 cycles of immunochemotherapy. This case suggests that dd-cfDNA may be an early detection tool in rare but potentially life-threatening cases of donor-derived malignancy, such as donor-derived PTLD.

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