The MDS Beacon™

A Phase 2 study by researchers at the M.D. Anderson Cancer Center in Houston has shown that suppression of the immune system with rabbit anti-thymocyte globulin (rATG) is a safe and effective treatment for low-risk myelodysplastic syndromes (MDS) and a low-blood cell condition known as aplastic anemia (AA).

While the rATG therapy induced a favorable response in patients as a first-choice therapy, AA patients had a higher response rate (92 percent) compared to MDS patients (33 percent).

Immunosuppressive treatments are being studied for AA and MDS because research suggests that these diseases may be caused by immune cells that destroy developing blood cells. Anti-thymocyte globulin therapies have been shown to regulate the immune system, and therefore hold promise for treating AA and MDS.

rATG was administered in combination with the immunosuppressant cyclosporine as well as granulocyte colony-stimulating factor (G-CSF) to stimulate the bone marrow.

Twelve low-risk MDS patients and 13 AA patients received rATG (3.5 mg/kg) daily for five days, although MDS patients older than 55 years received 2.5 mg/kg per day. All patients also took cyclosporine (5 mg/kg) orally every day for a minimum of six months, and G-CSF (5 µg/kg) by subcutaneous injection for up to three months. AA patients were evaluated a median of 12.2 months after starting treatment, while MDS patients were evaluated a median of 12.4 months after starting treatment.

Of the 12 MDS patients, 8 percent achieved complete remission, while 25 percent achieved a partial response. Complete remission for MDS is defined by the International Working Group as having a blood count of more than 1,000 neutrophils per µL and more than 100,000 platelets per µL. This does not necessarily mean that MDS is fully cured or that there are no cancer cells in the body, although there are no evident symptoms of the disease. MDS patients responded to treatment after a median of 111 days.

Of the 13 AA patients, 38 percent achieved complete remission, and 54 percent achieved a partial response. AA patients responded after a median of 93 days.

The main side effects of the treatment included low blood counts, fever, kidney failure, and electrolyte deficiency, but they were determined to be reversible and not significantly harmful.

Currently, severe AA patients who are not candidates for stem cell transplants are typically treated with horse anti-thymocyte globulin (hATG) in combination with cyclosporine. Previous to this study, rATG was usually administered to AA patients only after they relapsed after hATG treatment.

Researchers determined the rATG-cyclosporine-G-CSF regimen to be safe for both AA and MDS patients based on the study results. Future studies will likely investigate predictive factors for a positive response to this therapy in both AA and MDS patients, and whether rATG or hATG is superior as a first-line therapy for AA.

For more information, please see the related research article in Leukemia (abstract).