Mesenchymal Stem Cell Transplantation Potential Novel Treatment for Patients With Severe Graft-vs-Host-Disease

ATLANTA—For transplant patients with severe acute graft-versus-host disease (GVHD), a novel treatment option may be in the form of another transplant, this time with mesenchymal stem cells (MSCs), according to research presented at the American Society of Hematology annual meeting (abstract 143).

Following stem cell transplantation for leukemia, mild GVHD can be beneficial, as it is associated with a reduced risk of relapse, according to Katarina Le Blanc, MD, PhD, associate professor of hematology, Huddinge University Hospital, Stockholm. However, she said, "Severe GVHD, particularly when it involves the liver and gut, can be difficult to treat and has a high mortality rate. There is no known second-line therapy for GVHD that does not respond to steroids."

Dr. Le Blanc and her colleagues in the European Group for Blood and Marrow Transplantation (EBMT) are investigating an alternative therapy for GVHD that involves transplantation of MSCs. In addition to their capacity to develop into a variety of tissues, including bone, adipose tissue, and cartilage, these rare progenitor cells appear to have immunomodultory activity and inhibit T cell alloreactivity. Furthermore, they have been shown to home to a wide range of tissues following intravenous infusion.

Given these properties, EBMT researchers have carried out multiple studies investigating the use of MSCs for treating GVHD and enhancing stem cell transplantation. The MSCs are harvested using a standard bone marrow aspirate, but due to their low frequency in vivo, they must be expanded ex vivo in order to generate sufficient cell numbers for transplantation.

In the current study, investigators enrolled 16 patients to undergo MSC transplantation. Two patients were being treated for extensive chronic GVHD, while 14 patients had therapy-refractory grade 3-4 acute GVHD.

MSC donors included human leukocyte antigen (HLA)-identical siblings (n = 2), HLA-haploidentical donors (n = 12), and third-party HLA-mismatched donors (n = 10). Following harvest and expansion of MSCs, the cells were administered intravenously according to the body weight of the recipient. A median of 1.0 X 106 cells/kg (range, 0.4 to 9 X 106/kg) were infused. Patients received one (n = 9), two (n = 6), or three (n = 1) doses of MSCs.

Response Rate

Of the 14 patients treated for acute GVHD with MSCs, the overall response rate was 79% (11 patients). Complete response, including a resolution of all symptoms, occurred in 6 patients; 5 patients improved, 1 maintained stable disease, and 2 died early. With a follow-up ranging from 2 to 44 months after transplantation, the overall survival rate was 43% (6 patients). Four patients developed extensive chronic GVHD, and one patient had recurrent leukemia (following transplantation for relapsed acute myeloid leukemia). Both patients initially treated for extensive chronic GVHD demonstrated transient responses to MSC transplantation; one patient died from lymphoma related to Epstein-Barr virus infection. Dr. Le Blanc concluded that while the study was small and not comparative in nature, "I think it is a good start for us to initiate a larger trial to find out if this really is a novel way of treating severe GVHD."