CRISPR-Edited Stem Cell Transplant Shows Promise Against Aggressive Blood Cancers

A Breakthrough for Aggressive Blood Cancers

A gene-edited stem cell transplant that removes the CD33 protein from donor cells can shield patients from dangerous side effects whilst opening the door to more effective immunotherapies for acute myeloid leukaemia, according to a phase 1/2 clinical trial published on 12 May 2026 in Nature Medicine. The multicenter trial, led by John F. DiPersio at Washington University School of Medicine in St. Louis, enrolled 30 adult patients with AML or myelodysplastic syndrome at high risk of relapse across 15 sites in the U.S. and Canada.

How the Therapy Works

Patients received donor stem cells engineered using CRISPR-Cas9 to delete the CD33 surface protein, a molecule present on both cancer cells and healthy blood-forming cells that has long complicated immunotherapy approaches. The gene-edited product, called tremtelectogene empogeditemcel (trem-cel) and made by Vor Biopharma, performed comparably to standard transplants. All patients achieved engraftment by day 28, with platelet production returning by day 16 on average.

Nineteen patients then received maintenance doses of gemtuzumab ozogamicin, an FDA-approved antibody-drug conjugate that targets CD33. Critically, patients maintained healthy blood cell counts across all doses, a stark contrast to the dangerous drops typically seen when this therapy follows a standard transplant.

The Path to CAR-T Combinations

The logic is straightforward: CAR-T cell therapy has struggled against myeloid cancers because the proteins it attacks on cancer cells also sit on healthy donor stem cells, triggering toxic inflammatory responses. By removing CD33 from transplanted cells, any remaining CD33-positive cells in the body should be cancer, making them clean targets for immunotherapy. A separate case study published in October 2025 demonstrated this potential when a patient who relapsed after a CD33-deleted transplant received CD33-targeted CAR-T cells and remains cancer-free more than a year later.

Risks and the Road Ahead

The trial was not without setbacks. Seven patients died during the study, four from cancer progression and three from transplant-related causes including kidney failure, liver toxicity, and sepsis. Average survival was just over 14 months. Side effects mirrored those of standard transplants. Still, researchers say the findings lay the groundwork for pairing CD33-deleted transplants with CD33-targeted CAR-T cells, a combination that could fundamentally change treatment for cancers that have long resisted such approaches.