Allogeneic hematopoietic cell transplantation (AHCT) is an established effective anti-cancer treatment. It is often the only hope therapeutically for many patients with certain poor-prognosis hematologic cancers (e.g. leukemias, lymphomas) and auto-immune disorders. Though AHCT offers major therapeutic benefits, the procedure is burdened with a 60-80% risk of causing graft-versus-host-disease (GVHD) in the recipient, a debilitating and often fatal severe rejection of patient tissues by donor-originated T cells.
The high risk, morbidity, mortality, and treatment costs of GVHD currently limit AHCT to patients who have a lethal cancer and a short life expectancy.
Analysis of the T lymphocyte transcriptome of donors and recipients of a hematopoietic stem cells (HSC) graft showed that some donors are stronger alloresponders than others, and consequently more likely to elicit GVHD. This trait is under polygenic control by genes involved, amongst other functions, in cell proliferation. These findings suggest that the gene expression profile of the donor has a dominant influence on the development of GVHD in the recipient. The predictive diagnostic test is based on gene expression profiling using quantitative real-time polymerase chain reaction method (qRT-PCR) and will consist of a panel of genes well validated in 300 pairs of graft donor and transplanted patients who did or did not developed GVHD.
This test will enable optimized donor selection and could lead to the marked reduction of the incidence of GVHD from 60% currently down to less than 10%.