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Donor-derived cell-free DNA detects kidney transplant rejection during nivolumab treatment.

Hurkmans, Daan P; Verhoeven, Jeroen G H P; de Leur, Kitty; Boer, Karin; Joosse, Arjen; Baan, Carla C; von der Thüsen, Jan H; van Schaik, Ron H N; Mathijssen, Ron H J; van der Veldt, Astrid A M; Hesselink, Dennis A.
J Immunother Cancer ; 7(1): 182, 2019 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-31300068

BACKGROUND:

In solid organ transplant (SOT) recipients, transplant rejection during immune checkpoint inhibitor (ICI) treatment for cancer is a clinical problem. Donor-derived cell-free DNA (dd-cfDNA) can be detected in blood and is a sensitive biomarker for diagnosis of acute rejection in SOT recipients. To our best knowledge, this is the first case report of a kidney transplant recipient with advanced cancer treated with ICI who was monitored with dd-cfDNA. CASE PRESENTATION A 72-year old female with a long-standing renal transplant was diagnosed with advanced melanoma in 2018 and was treated with the anti-PD1 antibody nivolumab. Within 12 days after the first administration of nivolumab, dd-cfDNA ratio increased to 23%, suggesting allograft rejection. Her kidney transplant function deteriorated and acute rejection was confirmed by renal transplant biopsy. As the rejection could not be controlled despite immunosuppressive treatment, a transplant nephrectomy was necessary and haemodialysis was started. Immunological analysis of the renal explant showed infiltration of alloreactive, nivolumab-saturated, PD1+ cytotoxic T cells. After transplant nephrectomy, she experienced nivolumab-related toxicity and rapid disease progression.

CONCLUSION:

Clinicians prescribing ICIs should be aware that SOT recipients are at risk of transplant rejection as a result of T cell activation. Dd-cfDNA is a sensitive biomarker and should be further studied for early detection of transplant rejection. Immunological analysis of the kidney explant showed marked graft infiltration with alloreactive PD-1+ cytotoxic T cells that were saturated with nivolumab.