Relapse after stem cell transplant has haunted patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) for years. That changed in a new clinical trial from Washington University School of Medicine in St. Louis. Researchers used gene editing to remove the CD33 protein from donor stem cells. This let targeted immunotherapies attack cancer cells while leaving healthy transplanted blood cells untouched.
All 30 patients in the phase 1/2 trial achieved engraftment of the CRISPR-edited donor stem cells by day 28, demonstrating robust and consistent establishment of the new blood system.
John F. DiPersio, MD, PhD, led the study. He said the gene editing strategy works. "The results of this study show that a CD33-deleted stem cell transplant yields outcomes comparable to standard stem cell transplantation." He pointed to the chance to combine this method with CD33-targeted immunotherapies like CAR-T cells to help more patients.
One patient’s story stands out. After a CD33-deleted stem cell transplant, their cancer came back. Instead of running out of options, doctors used CD33-targeted CAR-T cells made from the original donor’s T cells. The patient went into complete remission. They stayed cancer-free for over a year. Their blood cell production returned to normal—now without CD33. This shows the real promise of the approach. Healthy donor cells survive therapies that would normally destroy them.
The study was conducted across 15 medical centers in the U.S. and Canada, and the average overall survival for participants was just over 14 months, as confirmed in an independent review.
Side effects looked like those from standard transplants. Patients had anemia, low platelets, fever, infections, and graft-versus-host disease. Seven of the 30 patients died during the study. Four died from cancer progression. Three died from transplant complications: kidney failure, liver toxicity, and sepsis. The average survival was just over 14 months. Nineteen patients received at least one cycle of gemtuzumab ozogamicin as part of a dose-escalation protocol, according to ScienceDaily reporting.
Why target CD33? The answer is clear. CD33 is found only on blood-forming cells. People who lack CD33 still make normal blood. This means the protein is not needed. After transplant, any cells with CD33 are likely cancerous. Therapies can then wipe out cancer while sparing the healthy, edited donor cells.
These results come as new strategies are badly needed for aggressive blood cancers. Recent coverage of experimental CAR-T cell therapy in other hard-to-treat cancers shows the same urgency. Here, CRISPR editing and targeted immunotherapy give patients a real way forward when standard treatments fail.
Vor Biopharma backed the study. Fifteen medical centers joined forces. The evidence is strong. Gene editing is not just for fixing genetic mistakes. It can build a window where powerful immunotherapies work without destroying the blood system patients need. This is a big step for the field. It will change how doctors think about relapse and remission in AML and MDS.
