CRISPR-Edited Stem Cells Protect Healthy Blood Cells in Trial for Aggressive Leukemia Therapy

A new clinical trial has demonstrated that using CRISPR gene editing to remove a specific protein from donor stem cells successfully protects those cells from targeted leukemia treatments. In a 30-patient study led by researchers at Washington University School of Medicine in St. Louis, the engineered cells, known as trem-cel, engrafted normally and shielded the patients' new blood systems from the toxic effects of a follow-up cancer therapy. The results, published in Nature Medicine and presented in September 2026, establish a method to attack residual disease without destroying the healthy cells required for survival.[3][4]

The approach solves a fundamental biological overlap that has long hindered treatments for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Both cancerous leukemia cells and healthy blood-forming stem cells display a surface protein called CD33. When doctors use targeted immunotherapies or antibody-drug conjugates to hunt down CD33-positive cancer cells, the drugs inevitably destroy the patient's healthy blood cells as collateral damage, leading to severe, sometimes fatal, cytopenias.[4]

To bypass this vulnerability, the research team partnered with Vor Biopharma to use CRISPR-Cas9 to edit the donor hematopoietic stem cells before transplantation. They snipped out the gene responsible for producing CD33. Because CD33 is not strictly necessary for normal blood cell function—individuals naturally lacking the protein show no apparent health deficits—the edited stem cells can still rebuild a patient's immune and blood systems, but they become effectively invisible to CD33-seeking drugs.[4][5]

In the Phase 1/2 trial, 30 adult patients with high-risk AML or MDS received the CRISPR-edited stem cells after standard myeloablative conditioning. All 30 patients achieved successful neutrophil engraftment within a median of 10 days, confirming that the CD33 deletion did not impair the stem cells' ability to multiply and differentiate into a functional blood system. Platelet production returned by day 16 on average, matching the recovery timelines of standard, unedited stem cell transplants.[3][5]

"We are encouraged by the results of this study showing that a CD33-deleted stem cell transplant looks very similar to the outcomes of standard stem cell transplantation," said John DiPersio, MD, PhD, director of WashU Medicine's Center for Gene and Cellular Immunotherapy. Once the new blood system was established, 19 patients were given gemtuzumab ozogamicin, an antibody-drug conjugate that targets CD33, at doses ranging from 0.5 to 2.0 milligrams per square meter.[3][5]

Historically, administering gemtuzumab ozogamicin after a transplant causes prolonged and dangerous drops in blood counts. However, patients with the trem-cel graft maintained their white blood cell and platelet counts across multiple doses of the drug, proving that the edited cells successfully shielded the new blood system from on-target toxicity. The trial demonstrated that the engineered invisibility held up under the stress of a targeted chemical attack.[3][4][5]

While the shielding effect was clearly established, the long-term impact on overall survival and relapse rates remains unproven. Seven patients died during the study—four from cancer progression and three from transplant-related complications including sepsis and renal failure. These outcomes highlight that while the gene editing protects blood counts, the underlying leukemias and the intensive transplant procedure itself remain highly dangerous. The trial was ultimately stopped early for fiscal reasons, limiting the ability to draw definitive conclusions about the long-term efficacy of the maintenance therapy.[3][4][5]

The proof-of-concept opens the door to pairing CD33-deleted stem cells with even more potent immunotherapies. Researchers are already exploring the use of donor-derived anti-CD33 CAR-T cells following a trem-cel transplant in a separate trial. By turning a shared myeloid antigen into a cancer-specific target, the CRISPR strategy could eventually expand the therapeutic window for cellular therapies in myeloid malignancies, offering a safer path to durable remission for patients with few other options.[4][5]