Exploring ECP’s Mechanism of Action Against GVHD

By Patrick Daly - Last Updated: October 4, 2022

An optimal second-line treatment has not been established for graft-versus-host disease (GVHD) that is resistant to first-line corticosteroids. One treatment that has shown promise is extracorporeal photopheresis (ECP), which involves collecting white blood cells, altering them with 8-methoxypsoralen and ultraviolet-A radiation, and reinfusing them back into the patient. However, the mechanisms by which ECP affects GVHD are not fully understood.

In a study in Clinical Lymphoma, Myeloma & Leukemia, researchers investigated whether ECP impacted the formation of neutrophil extracellular traps (NETs), a function of the neutrophil immune response. According to the study’s lead author, Idan Goldberg, ECP appeared to induce NET formation in a cohort of 6 patients.

This study enrolled 2 women and 4 men with chronic GVHD who received ECP treatment at the authors’ center. Researchers collected blood samples before initiation of ECP, after the first treatment, and 24 hours after the start of the cycle. Neutrophils were obtained from the samples and assessed for NET formation via neutrophil elastase activity and immunofluorescence.

According to the report, all 6 patients exhibited a sharp increase in NET formation after ECP. Specifically, neutrophil elastase activity level was increased from a mean of 2.21 ± 0.6 mU/mL at baseline to a mean of 13.82 ± 5.54 mU/mL immediately following treatment. Levels peaked at 17.35 ± 10.74 mU/mL 24 hours after cycle initiation.

Overall, Goldberg and colleagues felt their preliminary data suggested that ECP acts against GVHD at least in part due to promotion of NET formation. “Given the central role of neutrophils in the pathogenesis of GVHD, the contribution of NETs to GVHD, and to ECP mode of action, should be further investigated,” the authors closed.

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