Two recent studies in the journal Leukemia present a new approach for bone marrow donation and transplant that preclinical laboratory tests suggest could make the life-saving procedure safer and more effective for patients.

Researchers at the Cincinnati Children's Cancer and Blood Diseases Institute say their studies demonstrate that use of an experimental drug called CASIN in laboratory mice results in higher efficiency when harvesting blood stem cells from donors and less toxicity in transplant recipients.

Designed to repair the body's blood-making machinery inside the bone marrow, a stem cell transplant can be life-saving for people with cancers like leukemia or those battling immune deficiency diseases.

But prepping patients for transplant involves using toxic chemotherapy to kill off a person's existing and malfunctioning blood-making system. This allows it to be replaced with healthy blood stem cells called hematopoietic stem cells (HSCs).

In addition to toxicity for patients, the procedure does not always work. Harvesting effective donor HSCs can be a challenge. And once transplanted the cells often do not engraft in sufficient numbers to make the patient healthy, according to Yi Zheng, Ph.D., senior investigator on both studies and director of Experimental Hematology and Cancer Biology.

Getting Cells to Mobilize

In one Leukemia study, Zheng's team rationally designed the drug CASIN. The drug mimics the action of an important gene called CDC42 that helps regulate blood stem cells.

Tests in mouse models show that CASIN can effectively mobilize blood-making stem cells and promote their exit from the bone marrow. The study indicates that blood stem cells harvested from CASIN-treated donor mice have better long-term reconstitution potential following transplant than cells harvested with regimens currently used in the clinic.

In the second study, researchers used CASIN to precondition mouse transplant recipients to make the body's bone marrow compartments more receptive to new and healthy blood stem cells.

The drug does this by prompting existing blood stem cells to vacate the bone marrow and migrate to peripheral blood, which is located in circulating blood not sequestered to the bone marrow.

This lessens the amount of chemotherapy needed to precondition the bone marrow in transplant recipients. It could allow effective transplant preconditioning when a recipient is unable to tolerate a chemotherapy-based procedure.

"Our data demonstrate that the new regimen of CASIN application has the potential to improve both sides of the transplant practice. It mobilizes higher quality donor HSCs during stem cell harvest, and it would condition transplant patients beforehand to increase engraftment efficiency," Zheng said.

"This would be a major step forward, especially for the most vulnerable patients who cannot withstand the toxicity of chemotherapy conditioning regimens or are non-responsive to current blood-stem-cell mobilization regimens," Zheng said.