A Phase I/II multicenter trial led by Washington University School of Medicine reported that a CRISPR-Cas9 CD33-deleted allogeneic hematopoietic cell transplant can reduce recurrence risk in high-relapse acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The study, published in Nature Medicine, used gemtuzumab ozogamicin as maintenance after transplant. The trial enrolled 30 adult patients at high risk of relapse across 15 sites in the U.S. and Canada. Investigators reported that all patients achieved engraftment by day 28 and said outcomes were similar to standard stem cell transplantation, supporting the CRISPR-edited approach as a feasible strategy in myeloid disease where CAR-T is limited by on-target toxicity. John DiPersio, MD, PhD, the study’s corresponding author, said the results support future combination efforts with CD33-targeted immunotherapies, including CAR-T, to expand treatment options for aggressive myeloid cancers. For hematology programs, the work adds another example of gene editing being used to modify donor cell properties for immune safety while keeping transplant efficacy. Subsequent follow-up on relapse, durability and toxicity will determine whether the strategy becomes a platform for next-generation allogeneic gene-edited transplants.