@article{10.1172/jci.insight.153551, author = {Takayuki Inoue AND Motoko Koyama AND Katsuji Kaida AND Kazuhiro Ikegame AND Kathleen S. Ensbey AND Luke Samson AND Shuichiro Takahashi AND Ping Zhang AND Simone A. Minnie AND Satoshi Maruyama AND Shinichi Ishii AND Takashi Daimon AND Takahiro Fukuda AND Hirohisa Nakamae AND Takahide Ara AND Yumiko Maruyama AND Ken Ishiyama AND Tatsuo Ichinohe AND Yoshiko Atsuta AND Bruce R. Blazar AND Scott N. Furlan AND Hiroyasu Ogawa AND Geoffrey R. Hill}, journal = {JCI Insight}, publisher = {The American Society for Clinical Investigation}, title = {Peritransplant glucocorticoids redistribute donor T cells to the bone marrow and prevent relapse after haploidentical SCT}, year = {2021}, month = {11}, volume = {6}, url = {https://insight.jci.org/articles/view/153551}, abstract = {Patients with acute leukemia who are unable to achieve complete remission prior to allogeneic hematopoietic stem cell transplantation (SCT) have dismal outcomes, with relapse rates well in excess of 60%. Haplo-identical SCT (haplo-SCT) may allow enhanced graft-versus-leukemia (GVL) effects by virtue of HLA class I/II donor-host disparities, but it typically requires intensive immunosuppression with posttransplant cyclophosphamide (PT-Cy) to prevent lethal graft-versus-host disease (GVHD). Here, we demonstrate in preclinical models that glucocorticoid administration from days –1 to +5 inhibits alloantigen presentation by professional recipient antigen presenting cells in the gastrointestinal tract and prevents donor T cell priming and subsequent expansion therein. In contrast, direct glucocorticoid signaling of donor T cells promotes chemokine and integrin signatures permissive of preferential circulation and migration into the BM, promoting donor T cell residency. This results in significant reductions in GVHD while promoting potent GVL effects; relapse in recipients receiving glucocorticoids, vehicle, or PT-Cy was 12%, 56%, and 100%, respectively. Intriguingly, patients with acute myeloid leukemia not in remission who received unmanipulated haplo-SCT and peritransplant glucocorticoids also had an unexpectedly low relapse rate at 1 year (32%; 95% CI, 18%–47%) with high overall survival at 3 years (58%; 95% CI, 38%–74%). These data highlight a potentially simple and effective approach to prevent relapse in patients with otherwise incurable leukemia that could be studied in prospective randomized trials.}, number = {22}, doi = {10.1172/jci.insight.153551}, url = {https://doi.org/10.1172/jci.insight.153551}, }