PROJECT SUMMARY/ABSTRACT The PENN Medicine Cell Therapy and Transplant Program (PENN CTT) is among the largest and oldest hematopoietic cell transplant (HCT) programs in the nation. This active program sees patients of all genders, races, ethnicities, socioeconomic status and individuals with disabilities and disadvantaged backgrounds. PENN CTT conducts all forms of HCT including autologous and allogeneic (myeloablative and reduced intensity) from all sources including cord blood, matched and mismatched related and unrelated donors and has been a pioneer in gene modified T cell therapies for a myriad of malignant and non-malignant diseases. Dr. Edward Stadtmauer has been the PI of this BMT CTN CCC since its founding in 2001, currently the Chair of the Steering Committee, and has a number of leadership positions at PENN Medicine including Hematology-Oncology Division, Abramson Cancer Center (ACC) and the Cancer Service Line so access to institutional resources and patients for BMT CTN clinical trials is straightforward and this has been reflected in the strong accrual from our center. Dr. David Porter, the Director of the CTT Program and President-elect of the ASTCT is a co-investigator of this CCC for over 20 years. Additionally, two new co-investigators, Drs Elizabeth Hexner, Medical Director for our Center for Cellular Immunotherapies (CCI), and Noelle Frey, Director of Cellular Therapy have been very active in the Network activities and are well positioned for leadership succession. 587 patients have been accrued from PENN CTT to BMT CTN; among the top 10 of >140 centers participating. PENN CTT has demonstrated substantial intellectual leadership in the Network. PENN CTT investigators have served as members on 18 protocol teams (study chairs for 6) and members of 8 administrative and technical committees (chair of 3). PENN CTT remains consistently very active with 2175 HCTs conducted in 2018-2022; 1446 autologous, 628 allogeneic and 599 cellular therapies. The PENN CTT is supported by numerous world-class HCT patient care and research resources including the ACC which was ranked ‘Exceptional’ as a NCI CCC in 2020; the CCI led by our pioneer cellular immunobiologist Dr. Carl June; and the PENN-CHOP Blood Center focused on non-malignant blood disorders run by Charles Abrams a renowned hematologist and past President ASH. Our research proposal, “A phase 2 trial for patients with B cell Acute Lymphoblastic Leukemia (ALL) who achieve a measurable residual disease (MRD) negative remission after brexu-cel randomized to a second infusion of brexu-cel versus allogeneic HSCT or observation” was chosen among many alternatives from Penn to demonstrate an area of our expertise, based on our own pilot study work, fill a major clinical need and can be completed in a timely fashion. These attributes of strong clinical research, patient care, thought leaders in the field and a documented enthusiasm for and success in BMT CTN trials uniquely position PENN CTT t...