AUG 17, 2016 2:30 PM PDT

Bone Marrow Transplants without Toxic Chemotherapy

WRITTEN BY: Xuan Pham
It’s tragically ironic that in medicine, sometimes the cure is almost as harmful as the poison. This is the case for bone marrow transplant, which could have the nearly same chance of saving a patient as it does harming the patient.

But for the patients whose last resort is a bone marrow transplant, researchers at Stanford have good news. They’ve developed a way to remove diseased or damaged blood stem cells without the use of toxic chemotherapy agents. While these results have only been reported in mice, the team says if successful in humans, the technique could revolutionize regenerative medicine.

New way to transplant blood stem cells without toxic chemo | Image: wikimedia.com
A bone marrow transplant is a procedure that replaces a patient’s diseased blood stem cells with healthy ones from a matched donor. There are several conditions that warrant a bone marrow transplant. These often involve blood disorders, such as cancer of the blood (leukemia), sickle cell anemia, or thalassemia. In some instances, chemotherapy or radiation treatment can damage the bone marrow, necessitating a transplant.

Before doctors can transplant healthy donor cells into a recipient patient, they must first wipe out the diseased blood cells from the patient’s bone marrow. This requires extremely toxic treatments that increase the risk for life-threatening complications. "The chemotherapy and radiation used for transplant damage DNA and can cause both immediate problems and long-term damage to many tissues in the body," said Judith Shizuru, senior author of the study. "Among the many known toxic side effects, these treatments can cause damage to the liver, reproductive organs and brain, potentially causing seizures and impairing neurological development and growth in children." 
 

To bypass chemotherapy, Stanford scientists focused on a more natural way to kill the diseased blood cells: antibodies. In particular, they used c-kit to mark blood stem cells for destruction. Then, they also used an antibody against CD47, which allowed macrophages to swallow up the marked blood stem cells.

In mice studies, the combination of antibodies successfully cleared out blood stem cells without adverse reactions. "If it works in humans like it did in mice, we would expect that the risk of death from blood stem cell transplant would drop from 20 percent to effectively zero," said Shizuru.

The applications for this technique could truly shift the limits of transplant medicine. Currently, transplant recipients are tethered to immunosuppressant drugs for a lifetime. "Even if you are on immunosuppressants, most organ transplants diminish in function or fail over time, and the immunosuppressive drugs themselves make the patient more susceptible to life-threatening infections or newly forming cancers," said Weissman, director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine. But if blood stem cells can be transplanted simultaneously with the organ, the recipient’s immune system may be able to cope with the new organ without rejection. "The donor blood stem cells re-educate the immune system of the patient, and the transplanted organ doesn't get kicked out,” explained Shizuru.

Furthermore, could this technique have the potential to treat blood-related disorders like sickle-cell anemia and thalassemias? The team is very hopeful. 
 

Additional source: Stanford University press release
About the Author
  • I am a human geneticist, passionate about telling stories to make science more engaging and approachable. Find more of my writing at the Hopkins BioMedical Odyssey blog and at TheGeneTwist.com.
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