TKI Therapy Investigated to Prevent Graft-Versus-Host Disease-Related Scleroderma
Scleroderma can often be a side effect of chronic graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation, as it occurs in 15.5% of chronic GVHD patients within five years. Patients are diagnosed with a condition known as sclerodermatous chronic GVHD (scGVHD) and are at a high risk for morbidity and late non-relapse mortality.
scGVHD is marked by a distinct involvement of the skin and is resistant to many standard therapies. As a result, researchers are interested in finding new ways to treat scGVHD and look for similarities among patients to determine potential pharmacological targets.
Some recent findings were summarized by a group at the City of Hope in Duarte California in the journal Bone Marrow Transplantation. Experiments conducted by the group in “Sclerodermatous Chronic GVHD in Patients Receiving Tyrosine Kinase Inhibitors after Allogeneic Hematopoietic Cell Transplantation” were motivated by the fact that scGVHD patients have elevated serum concentration of anti-platelet derived growth factor receptor (PDGFR) and anti-transforming growth factor-β (TGF-β) agonistic antibodies. Other groups have shown efficacy of imatinib, a tyrosine kinase inhibitor (TKI), in inhibiting PDGF and TGF-β signaling pathways and reducing matrix production by cells cultured from scGVHD patients.
With this in mind, the group conducted a retrospective analysis to determine the efficacy of TKIs post-stem cell transplantation. Eighty-nine patients with Ph+ acute lymphoblastic leukemia or chronic myeloid leukemia who received a transplant between 2005 and 2010 were found in a database at the City of Hope. Of these patients, 55 received TKI therapy soon after treatment for approximately 9 months. The other 34 patients had not been given TKIs due to resistance or intolerance to the agents.
After two years, 10.3% of all patients developed scGVHD. Within the TKI group, 7.4% developed scGVHD, and 14.8% of non-TKI patients developed scGVHD. The difference was insignificant (p=0.46). Onset of scGVHD was longer for the TKI group (4.3 months) than the non-TKI group (3.9 months), but again there was no significant difference (p=0.91).
At the end of the study, the researchers concluded that there were no clear benefits of TKIs on preventing scGVHD, but they acknowledged the limited sample size and retrospective nature of the study.