(565) Donor-Derived Cell-Free DNA in Cancer Survivors Following Heart Transplantation

• Published in: The Journal of heart and lung transplantation Vol. 42; no. 4; p. S255
• Main Authors: Slomovich, S., Rubinstein, G., Moeller, C.M., Lotan, D., Mehlman, Y., Donald, E., Batra, J., Oren, D., Oh, K., Clerkin, K., Fried, J., DeFilippis, E., Topkara, V., Kleet, A., Colombo, P.C., Yuzefpolskaya, M., Lin, E.F., Lee, S., Majure, D., Latif, F., Sayer, G.T., Uriel, N., Raikhelkar, J.K.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.04.2023
• ISSN: 1053-2498; 1557-3117
• DOI: 10.1016/j.healun.2023.02.580

Improvements in cancer therapies have led to a growing population of cancer survivors (CS) who are recipients of heart transplantation (HT). CS have been shown to have long-term alterations in immune function from prior cancer treatments leading to challenges in management of immunosuppression. Post-HT donor-derived cell-free-DNA (dd-cfDNA) testing is a noninvasive method used to detect allograft rejection. We sought to evaluate the effect of pre-HT malignancy on dd-cfDNA and post-HT outcomes. All consecutive patients who underwent HT at our institution between 1990 to 2022 with at least one dd-cfDNA result were included in the analysis. Dd-cfDNA results in the CS group were compared to patients free from malignancy (FFM). Dd-cfDNA was considered positive if >0.12%. For the purpose of this analysis, samples reported as <0.12% were analyzed as 0.11%. A total of 588 patients were identified. There were 47 (8%) patients in the CS group and 541 (92%) patients in the FFM group. CS were older at the time of transplant (60 vs 54 years, p = 0.03) with a median time from active malignancy to HT of 8 [3.5, 16.5] years. Leukemia/lymphoma was the most common cancer type (27.7%) followed by breast, prostate, and gastrointestinal (13% each). In the CS group, 38.3% of the dd-cfdNA samples were positive compared to 29.4% in the FFM group (p=0.004). The prevalence of donor-specific antibodies (DSA) was similar in the CS and FFM groups, 23.7% and 23.4%, respectively (p=0.86). There was no difference in biopsy-proven cellular and antibody-mediated rejection or graft failure during the follow-up period (1450 and 1830 days in CS vs. FFM groups, respectively; p=0.62). In our cohort, the CS group had higher rates of positive donor-derived cell-free-DNA results compared to patients without preexisting malignancy. Future studies are needed to assess the immunosuppression protocols of both groups and assess if this can be the cause of the differences we found.