A Phase I/II multicenter trial reported that CRISPR-Cas9 CD33-deleted allogeneic hematopoietic cell transplantation, paired with gemtuzumab ozogamicin maintenance, achieved engraftment by day 28 in high-risk AML and MDS patients, according to results published in Nature Medicine. The approach removes CD33 from donor cells to reduce relapse risk while acknowledging toxicity tradeoffs that have historically limited targeted options. Investigators at Washington University School of Medicine in St. Louis and Siteman Cancer Center, along with 14 other sites in the U.S. and Canada, treated 30 adults at high risk of relapse. The maintenance therapy leverages a CD33-directed antibody-drug conjugate already approved for CD33-positive AML. The trial matters because it suggests gene-edited stem cell transplantation could compete with or complement CAR-T strategies in myeloid cancers where shared targets create safety constraints.