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ASH: Stem Cells Rescue Some Patients With Severe GvHD


ORLANDO -- Mesenchymal stem cells derived from bone marrow show promise for severe steroid-resistant graft-versus-host disease, reported European investigators here.

ORLANDO, Dec. 11 -- Mesenchymal stem cells derived from bone marrow show promise for severe steroid-resistant graft-versus-host disease, reported European investigators here.

In a study of 52 patients who developed steroid-resistant GvHD after bone-marrow transplantation for hematologic malignancies, there was a 68% overall response rate to infusion of mesenchymal stem cells from adult bone marrow, said Katrina LeBlanc, M.D., of the Karolinska University Hospital Huddinge in Stockholm.

The success of the treatment may depend on anti-inflammatory and immunomodulatory properties of the mesenchymal stem cells derived from bone marrow, said Dr. LeBlanc speaking for a European bone marrow consortium at the American Society of Hematology meeting.

"In severe forms of GvHD that are not responsive to steroids, mortality is very high, and for the most severe forms it's nearly 100%," Dr. LeBlanc said.

Bone-marrow derived mensenchymal stem cells provide the stroma for hematopoeitic cells, and can also give rise to bone, muscles, cartilage, and connective tissue, she noted.

Undifferentiated mesenchymal stem cells appear to have immunomodulatory properties, will reduce an inflammatory response, and suppress production of activated lymphocytes, Dr. LeBlanc said.

In the first patient in whom this therapy was tried, a young boy with a severe form of GvHD, "we saw a very remarkable effect, both in terms of reduced inflammation in the GI tract, but also in terms of a very rapid recovery of the intestinal epithelium, so that the patient could go back to eating normally and not be on IV nutrients anymore," Dr. LebLanc said.

Since that time, her hospital and other European centers, have formed a mesenchymal stem cell expansion consortium.

On behalf of the consortium investigators, Dr. LeBlanc presented results of a study of mesenchymal stem cell infusions in 52 patients with severe GvHD unresponsive to steroids.

The patients had grade III or IV acute gastrointestinal GvHD following a hematopoietic stem cell transplant, and were given either one, two, three, or five doses of mesenchymal stem cells that had been harvested from either HLA identical sibling, haploidentical donors, or HLA-mismatched donors.

They saw an overall response rate of 68%, with children faring slightly better than adults, and early treatment appearing to be associated with better outcomes than late treatment.

Of the 52 patients, 22 are alive, 11 of them well, and the 11 others with chronic GvHD. Of the 30 patients who died, 17 did not respond to the mesenchymal stem cell treatment and died from GvHD. An additional eight responders were severely immunocompromised by GvHD and died from infections. The remainder died from causes not related to GvHD or to the therapy, Dr. LeBlanc said.

The investigators are embarking on a phase III randomized, double blind trial to further study the effects of mesenchymal stem cell infusions on severe GvHD.

"In a very short time, this novel therapy had provided new hope for patients, a very, very rapid response in a large number, aborting this autoimmune/alloimmune reaction, and providing a platform for future research to try to perfect the therapy," commented Stephen Emerson, M.D., Ph.D., of the University of Pennsylvania. Dr. Emerson was not involved in the study and declared no conflict of interest.

Dr. LeBlanc had no relevant conflicts of interest to declare.

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