ISAL 2025 | APOE2 as a risk factor for adverse post-transplant outcomes in AML

APO lipoprotein E is a human lipid transporter which has recently been discovered to be involved in anti-cancer immunity and this inspired us to examine APOE isoforms in the context of allogeneic stem cell transplantation, one of the oldest forms of cancer immunotherapy, and we discovered that APOE2 which is originally associated with longevity in the general population is an adverse risk factor for post transplant survival. We discovered that in our Munster University Hospital cohort and validated our findings in an external multicenter cohort of the collaborative biobank of seven transplant centers in Germany. In contrast in AML patients not undergoing transplant from Beat AML, APOE2 was not associated with inferior survival prompting us to to assume that the adverse outcome of APOE2 patients was tightly linked to the transplant procedure. And drivers of adverse outcomes in APOE2 patients were severe chronic GvHD and non relapse death. Finally we investigated the impact of donor APOE germline variation as well and discovered that even in APOE2 negative patients receiving APOE2 positive allografts, there was a higher risk of severe acute and severe chronic GvHD. In summary our findings indicate that APOE2, which is originally associated with longevity in the general population, emerges as a germline risk allele for post transplant complications in AML.

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