PROJECT SUMMARY/ABSTRACT Over the last 22 years, the BMT CTN has effectively addressed key issues in hematopoietic cell transplantation (HCT), including donor selection, choice of preparative regimens, prevention of post-transplant infection, prevention and treatment of graft-versus-host disease, prevention of relapse, the role of transplant vs. non- transplant therapy, and indications for HCT in the treatment of specific diseases, through the conduct of 61 clinical trials. The Fred Hutch Program has played an important role in the success of the BMT CTN since its inception, serving as one of its Core Clinical Centers. There are many features of the Fred Hutch Program that enhance its value as a Core Clinical Center. (1) The volume of clinical activity allows us to successfully recruit and enroll patients on BMT CTN clinical trials, including patients with rare diseases. The Hutch’s performance in reaching its BMT CTN accrual targets over the last four years has been rated by the BMT CTN as “outstanding.” (2) Our extensive experience with HCT and adoptive cellular therapy provides outstanding clinical outcomes, and we exceeded the 95% confidence limits for survival as calculated by the center-specific outcomes analysis of the Center for International Blood and Marrow Transplant Research (CIBMTR) in 2018 and 2022. (3) The faculty of the Fred Hutch Program includes a large number of investigators, all focused on various aspects of HCT and cellular therapy. The breadth and depth of this group helps ensure that we will continue to provide important scientific contributions to the network. Since 2018, our group has been rated as “outstanding” by the BMT CTN for our scientific and administrative efforts. (4) The Fred Hutch has extensive experience with novel cell therapies including stem cell expansion, genetic engineering of T cells, and correction of inborn errors, which are areas of specific interest noted by the NHLBI and the NCI. (5) Our proposed phase 3 clinical trial of preemptive treatment for chronic GVHD fulfills one of the recommendations of the 2020 NIH Chronic GVHD Consensus Conference. (6) The faculty of the Fred Hutch have enthusiastically collaborated with other members of the BMT CTN to help achieve the network’s research goals over the past funding periods with an overall rating of outstanding from 2018-2022. We remain committed to the Network’s success.