FROM JOURNAL OF CLINICAL ONCOLOGY
Repeat infusions of mesenchymal stromal stem cells appear to inhibit the development of chronic graft-versus-host disease (cGVHD) in patients who have undergone an allogeneic stem cell transplant.
The 2-year cumulative incidence of cGVHD among those randomized to receive repeated infusions of umbilical cord–derived mesenchymal stromal cells (MSCs) was half that of controls treated with a saline placebo, based on results from a randomized phase II, double blind trial in 124 patients with hematologic malignancies who underwent an HLA-haploidentical allogeneic hematopoietic stem cell transplantation (HSCT).
“Our goal was to minimize the incidence of cGVHD, reduce the severity of cGVHD, and demonstrate the safety of MSC infusions. We performed repeated infusions of MSCs once a month for a total of four rounds for each patient. Over the median 47-month posttransplantation period, the incidence of cGVHD was lower in the MSCs group than in the non-MSCs control group,” Lei Gao, MD, of the Third Military Medical University in Chongqing, China, and colleagues wrote in the Journal of Clinical Oncology (2016 Jul 11. doi: 10.1200/JCO.2015.65.3642 ).
Although cGVHD is associated with a reduced risk of leukemia relapse, it is still the leading cause of nonrelapse deaths after HSCT. The incidence of cGVHD is higher among recipients of HLA-haploidentical HSCT, in which the donor and recipient have identical HLA alleles on only one copy of chromosome, than among HLA-matched recipients, who have identical alleles on both copies.
The researchers randomly assigned 124 patients who had undergo HLA-haploidentical HSCT to receive either placebo or MSCs at a dose of 3 x 107 cells/100 mL per month for four cycles beginning 4 months after HSCT
Of the 124 randomized patients, 12 discontinued the study due to cGVHD or disease progression.
The 2-year cumulative incidence of cGVHD among patients treated with MSCs was 27%, compared with 49% for placebo-treated controls (P = .021). Seven patients in the control group but none in the MSC-treated group developed typical lung cGVHD (P = .047).
The investigators also observed increases in memory B lymphocytes and regulatory T cells, and in the ratio of type 1 to type 2 T-helper cells, as well as a decrease in natural killer cells.
The finding that the MSC infusions increased the number of regulatory T cells while decreasing the incidence of cGVHD suggests that regulatory T cells play an inhibitory role, the investigators said.
The study was supported by the Chinese Academy of Sciences. Chinese National Natural Science Foundation, and other Chinese government grants. The authors reported having no relationships to disclose.