Donor-derived Acute Myeloid Leukemia in solid organ transplantation.
Academic Article
Overview
abstract
We report the transmission of acute myeloid leukemia (AML) undetected at donation from a deceased organ donor to two kidney and one liver recipients. We reviewed the medical records, and performed molecular analyses and whole exome sequencing (WES) to ascertain AML donor origin and its molecular evolution. The liver recipient was diagnosed eleven months after transplantation and died from complications two months later. The two kidney recipients (R1 and R2) were diagnosed nineteen and twenty months after transplantation and both received treatment for leukemia. R1 died of complications eleven months after diagnosis, while R2 went into complete remission for forty-four months, before relapsing. R2 died ten months later of complications from allogenic bone marrow transplantation. Microsatellite analysis demonstrated donor chimerism in circulating cells from both kidney recipients. Targeted molecular analyses and medical records revealed NPM1 mutation presence in the donor and recipients, while FLT3 was mutated only in R1. These findings were confirmed by WES, which revealed additional founder and clonal mutations, and HLA genomic loss in R2. In conclusion, we report the first in-depth genomic analysis of AML transmission following solid organ transplantation, revealing distinct clonal evolution, and providing a potential molecular explanation for tumor escape.
