*Purpose: This case series highlights our institution’s experience with solid-organ transplant (SOT) associated acute graft versus host disease (aGVHD), a rare and deadly complication of SOT whereby donor-derived T-lymphocytes react against recipient tissues, for which best practice surveillance and treatment protocols remain ill defined.

*Methods: After IRB approval, our institutional EMR (EPIC from Jan 1990 to Dec 2020) was queried for SOT recipients evaluated by chimerism testing. Demographics, including clinical, laboratory, and histological features were captured and individuals with aGVHD diagnoses identified.

*Results: Seven patients with SOT related aGVHD diagnosis were identified (aged 32-68y; 4/7 male; 5 liver recipients; 2 kidney-pancreas recipients). Per available data, five had HLA mismatches >7/12 (HLA-A/B/C/DR/DQ/DP) in the host to graft direction, one was a 12/12 match. Donors (aged 16-68y; 5/7 male) averaged 14 years younger than recipients. Donor-recipient ABO, CMV, and EBV sero-mismatches were identified in 0/7, 2/6, and 0/6, respectively. Two patients had HCV+ histories. Average time from transplant to development of GVHD was 48 days (24-84d), as defined by donor chimerism (>2%) in presence of clinical aGVHD features. Commonly affected organs: skin (100%), bone marrow (86%), and gastrointestinal tract (43%). Clinical signs included rash, cytopenia, fever, and diarrhea. At the time of SOT aGVHD diagnosis, all were on mycophenolate mofetil immunosuppression, with adjunctive tacrolimus (6/7) or cyclosporine (1/7). Bone marrow biopsies in 5/7 demonstrated hypocellularity. Donor chimerism at diagnosis ranged from 23-95%. Five patients had follow-up chimerism data – only 1 (Patient A) had chimerism decrease to <2% with treatment, the sole case series survivor. Notably, Patient A and one other had LDH <200 while the rest 5 had LDH >500 at diagnosis. All received high dose steroids with varying adjunctive treatments: ATG (2/7), photopheresis (3/7), alemtuzumab (2/7), ruxolitinib (1/7), belatacept (1/7), eculizumab (1/7), and tocilizumab (1/7). Patient A received ATG and steroids, both initiated within two days of diagnosis. 2^nd patient receiving ATG did not start until day 17 after diagnosis. Average time from diagnosis to death was 35 days (4-97d).

*Conclusions: In contrast to the limited literature, our window of aGVHD occurrence was 3-12 weeks (vs 10d-6 weeks); HCV was seen in 2/6 cases; and HLA matching (lack of mismatches) did not appear associated with SOT aGVHD incidence. This represents the largest case series of SOT aGVHD with complete accompanying HLA typing. Findings suggest LDH as a prognostic marker for SOT related aGVHD and that prompt initiation of ATG in conjunction with high dose steroids should be considered as a first line treatment. Further work will compare these 7 patients with 90+ other SOT recipients without aGVHD evaluated by chimerism testing.

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