The Innate Immune Sensor Sting Promotes CD8+ T Cell-Mediated Gvhd after Preclinical Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

in MRDpts, ATG did not affect RI (24.3 vs. 21.5% at 2y in MRD ¡ / no ATG and MRD ¡ /ATG; HR 0.80, P = 0.17), but was associated with lower incidence of grade II-IV and III-IV aGVHD, overall and extensive cGVHD and NRM (HR 0.71 P = 0.04, HR 0.37 P = 0.0009; HR 0.55 p < 10 ¡4 , HR 0.42 P < 10 ¡5 and HR 0.66 p = 0.05, respectively). As a result, ATG was associated with improved LFS, OS and GRFS (HR 0.74 P = 0.02, HR 0.69 P = 0.01 and HR 0.62 P = 0.00001). In MRD + pts, ATG was associated with lower incidence of overall and extensive cGVHD (HR 0.56 p = 0.03, HR 0.40 P = 0.01, respectively), without a significant impact on any other alloSCT outcomes, including RI (38.8% vs 38.6% in MRD + /no ATG and MRD*/ATG; HR 1.02 P = 0.92). Conclusions: ATG reduces acute and cGVHD incidence and severity in AML pts undergoing alloSCT in CR1, resulting in improved GRFS. AML relapse risk remained unmodified by ATG use, even in the high risk subset of MRD+ patients' pre-alloSCT. Therefore, the use of ATG is not detrimental, and can allow for a significant clinical benefit in all CR1 AML patients who are candidate for alloSCT.