Among patients undergoing allogeneic hematopoietic cell transplantation (HCT), depleting naïve T cells from peripheral blood stem cell (PBSC) allografts may reduce the risk of severe acute or chronic graft vs host disease (GVHD), according to research published in the Journal of Clinical Oncology.

Allogeneic HCT is commonly used among patients with hematologic cancers, and may be curative in a subset of patients. T cells (including alpha and beta T cells) in the graft trigger a graft vs leukemia effect, which is both the intent of the treatment and the basis of patient reaction to the therapy.

Among a subset of patients, however, alloreactive T cells may damage the patient’s cells, resulting in GVHD, which can take either acute or chronic forms. Chronic GVHD may occur in up to 60% of patients who undergo allogeneic HCT, and is linked with both nonrelapse mortality (NRM) and lower quality of life. Patients who develop chronic GVHD may, furthermore, require extended immunosuppression therapy.


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Naïve T cells, which are subsets of alpha and beta T cells, have previously been linked with an increased risk of GVHD. A mouse model showed that depleting naïve T cells may lower the risk of both acute and chronic GVHD. For this set of phase 2 trials, researchers investigated whether depleting naïve T cells in patient PBSC reduced the risk of GVHD among patients undergoing allogeneic HCT.

Overall, 138 patients with naïve T cell-depleted PBSC were included. The median age in the overall cohort was 37 years (range, 1-60), 41% of patients were male sex, 43% of patients had acute myeloid leukemia, 46% of patients had acute lymphoblastic leukemia, and 62% of patients had standard-risk disease.

The median follow-up was 4 years. In the full cohort, mild chronic GvHD occurred in 7% of patients (95% CI, 2-11), moderate in 1% (95% CI, 0-2), and severe in 0%. Grade 2 acute GVHD occurred, however, in 71% (95% CI, 64-79) of patients, while grade 3 acute GVHD occurred in 4% (95% CI, 1-8), and grade 4 occurred in 0%.

Rates of acute and chronic GVHD did not, furthermore, differ significantly by whether donors were matched related or matched unrelated.

At 3 years, the overall survival rate was 77% (95% CI, 71-85); the relapse rate was 23% (95% CI, 16-30). The nonrelapse mortality rate at 100 days was 4% (95% CI, 1-8) and at 3 years was 8% (95% CI, 3-13).

Disclosure: The study author(s) declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference

Bleakley M, Sehgal A, Seropian S, et al. Naive T-cell depletion to prevent chronic graft-versus-host disease. J Clin Oncol. Published online January 10, 2022. doi:10.1200/JCO.21.01755