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Bone marrow transplants may be possible without toxic pre-treatment, new research suggests

Bone marrow transplants may be possible without toxic pre-treatment, new research suggests

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The world of hematopoietic stem cell (often called bone marrow) transplants appears to be poised for a very big, very good shake-up, and I couldn’t be happier.

The news comes on the heels of the publication of research by Stanford stem cell specialist and pediatrician Agnieszka Czechowicz, MD, PhD, and her colleagues indicating that hematopoietic stem cell transplantation might one day allow organ recipients to accept immunologically mismatched solid organs. The key, they found, was the use of an antibody called anti-CD117 to specifically target and eliminate hematopoietic stem cells in mice while sparing the animals’ mature blood and immune cells.

Now several Stanford researchers, including Czechowicz; oncologist Judith Shizuru, MD, PhD; and postdoctoral scholar Wendy Pang, MD, PhD, have published new results in Blood showing it’s possible to use a similar antibody-based treatment to safely and efficiently kill off either healthy or diseased human hematopoietic stem cells in a mouse.

Our release explains the setup:

Hematopoietic stem cells are found in the bone marrow. They give rise to all the cells of the blood and immune system. Blood cancers, such as leukemia, arise when the stem cells or their progeny begin dividing uncontrollably; other genetic conditions such as sickle cell anemia or thalassemia occur when the hematopoietic stem cells generate malformed red blood cells or hemoglobin.

Often the best chance for a cure for these and other diseases originating in the bone marrow is to eliminate the patient’s own defective hematopoietic stem cells and replace them with healthy stem cells from a closely matched donor. But in order to do so, the patient must be able to withstand the pre-treatment, known as conditioning. Most conditioning regimens consist of a combination of chemotherapy and radiation in doses high enough to kill stem cells in the marrow.

Shizuru and her colleagues studied a mouse model of a class of human blood diseases called myelodysplastic syndromes, or MDS. MDS primarily affects older adults, but they are less able to withstand the conditioning regimen due to their age and the likelihood of additional, complicating medical conditions. The researchers found that treatment with an anti-CD117 antibody called SR1 could eliminate diseased hematopoietic stem cells isolated from people with low-risk MDS and help healthy hematopoietic stem cells engraft. (Stem cells isolated from people with high-risk MDS were also significantly reduced in number but began to rebound after treatment.)

As Pang explained:

SR1 directly targets the disease-initiating cells for elimination in the mice, even though these cells typically have a significant competitive advantage. This is the first antibody directed against CD117 that has been proven to clear both normal and diseased human cells from the recipient. We are very pleased with the results.

Taken together the results of these recent publications suggest a coming sea change in how patients with blood and immune disorders, including cancers, receive hematopoietic stem cell transplants and they could vastly increase the number of people who could benefit from the treatment.

The work has paved the way for at least two clinical trials, one for children with an immune disorder called severe combined immunodeficiency at Stanford and the University of California, San Francisco. (Initial results appear promising). The second, which is still in the planning stages, will target MDS patients using a version of the SR1 antibody optimized for use in humans.

“We are very hopeful that this body of research is going to have a positive impact on patients by allowing better depletion of diseased cells and engraftment of healthy cells,” Shizuru said.

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