In an article published online in Blood, researchers from biotechnology firm Cellerant Therapeutics and Stanford University presented animal data that suggested by using purified stem cells, rather than whole bone marrow, it might be possible to transplant lupus patients using a milder form of treatment and less-stringently matched donors.

Together, the two changes would mean the procedure could be a viable option for a larger fraction of lupus patients. Currently, transplantation is a so-called "salvage treatment," which itself is harsh enough to kill in excess of 10 percent of patients subjected to it.

There are several reasons transplantation currently is an option of last resort. Most bone marrow transplants for lupus are autologous - that is, the patient's own bone marrow is harvested, and the patient is re-transplanted with them in an effort to "reset the immunological clock," as the authors write in their paper. In order for such resetting to occur, the patient is treated with high doses of radiation to kill off the resident bone marrow, a procedure known as myeloablative conditioning.

While there have been encouraging results of allogeneic transplants, or transplants from a related donor, those are rare for two reasons. Currently, donors tend to be matched siblings - those whose immune systems have the same human leukocyte antigen, or HLA, molecules. Unfortunately, the chances of a sibling being a matched donor is 1-in-4, making it a rare commodity. Graft-vs.-host disease, in which mature T cells from the transplanted bone marrow attack the recipient tissues, also is a concern.

In animal studies, researchers from San Carlos, Calif.-based Cellerant showed that mice with an animal version of the autoimmune disease systemic lupus erythematosus that were transplanted with purified stem cells from haplo-mismatched donors - that is, donor mice whose HLA type did not match those of the recipients - showed improvement in the major symptoms of lupus. Those included decreased protein in the urine (which is indicative of kidney problems) and of autoantibodies to nuclear DNA.

"We were able to halt the actual autoimmune disease" in the animals, senior author Julie Christensen told BioWorld Today.

Christensen said that the paper suggested it could be possible to use parents or mismatched siblings for bone marrow donation.

The researchers also compared myeloablation, or the complete destruction of the donor immune system, with non-ablative conditioning, which allows the recipient immune system to survive. They found that non-ablative conditioning prior to stem cell treatment not only was sufficient to ensure engraftment, but that the procedure also resulted in improved overall survival. The recipient subjects developed durable mixed chimerism, with an immune system that was a mix of donor and recipient cells.

"The two immune systems could live side by side," Christensen said. Transplanting T cells, which are the culprits in graft-vs.-host disease, was not necessary for tolerance to develop.

If the situation in humans turns out to be similar to what the scientists observed in their mice, the combination of gentler treatment and a wider range of potential donors might move transplantation up from salvage treatment.

Christensen noted that in the animal studies, mice that had advanced lupus profited far less from the transplant that those in earlier stages. She hopes the findings will encourage doctors to consider transplantation as a possibility for their patients before those patients are down to last-resort options. "That's the important thing, to convince rheumatologists" that their patients will benefit, she said.