Thalidomide appears to be effective in eliminating or reducing transfusions for certain patients with myelodysplastic syndromes, according to a recent article published in the journal Blood.

A myelodysplastic syndrome is a disease in which the cells in a person’s bone marrow are not functioning normally. The bone marrow (and circulating blood) contains early blood-forming cells called stem cells, which grow and mature into the 3 blood cell types: white blood cells which protect the body from infection; red blood cells which carry oxygen to the tissues; and platelets which help the blood to clot. In the case of myelodysplastic syndromes, not enough normal blood cells are being produced and/or the blood cells die prematurely. This condition is sometimes referred to as a pre-leukemia or “smoldering” leukemia because it often develops into leukemia, a type of cancer. Some patients with myelodysplastic syndrome also have additional abnormalities, including genetic abnormalities of the blood cells, a high number of immature blood cells (called blasts) in the bone marrow, or decreasing numbers of red blood cells, white blood cells, or platelets. These individuals are at a higher risk for a more rapid progression to leukemia than are those who have more favorable cell features.

Treatment of myelodysplastic syndromes often consists of the infusion of red blood cells or platelets to compensate for the inadequate production of these cells in the bone marrow. This therapy may ease the signs and symptoms of disease, such as anemia or fatigue, and may prolong survival time. However, transfusions are associated with pain, time, infection, rejection of donor cells and medical cost. Researchers are investigating novel therapies for patients with myelodysplastic syndromes.

Thalidomide is a substance known for its anti-angiogenesis properties. Angiogenesis is the formation of new blood vessels in the body and is a crucial component for the development of cancer. Blood vessels are needed to supply cancer cells with essential nutrients from the blood. Anti-angiogenesis is the inhibition of the formation of new blood vessels. By stopping blood vessels from forming, cancer cells are “starved” of nutrients, ultimately inhibiting cancer development and growth. In addition, thalidomide is also considered an immunodmodulatory agent. Recent research suggests that thalidomide is involved in the inhibition of chemical signals that stimulate the immune system. Elevated levels of these chemicals appear to be more prominent in patients with some blood disorders including myelodysplastic syndromes. However, the exact mechanisms through which the immune system plays a role in myelodysplastic syndromes is not entirely clear. Previous clinical studies have demonstrated that thalidomide achieves significant anti-cancer responses in patients with multiple myeloma, a cancer of the blood, and more evidence is mounting indicating that thalidomide has anti-cancer effects in various other cancers.

Researchers from the Rush Cancer Institute recently conducted a clinical trial evaluating thalidomide in 83 patients with myelodysplastic syndrome. Patients were discontinued from the study if side effects could not be tolerated or their disease progressed while on thalidomide. Fifty-one patients were able to complete therapy. Of the patients that completed therapy, 16 achieved an anti-cancer response, and 10 patients who previously required transfusions became transfusion independent. Patients who were discontinued from the study tended to have a higher number of blasts in their blood and a lower number of platelets prior to treatment with thalidomide.

These results indicate that thalidomide may be effective in preventing low blood cells levels and therefore reducing or eliminating transfusions in some patients with myelodysplastic syndromes. Patients appearing to derive the most benefit from thalidomide tend to have lower levels of blasts and higher levels of platelets. Further study involving thalidomide will include clinical trials evaluating thalidomide in combination with other treatment modalities for patients with myelodysplastic syndromes. Patients with myelodysplastic syndrome may wish to speak with their physician about the risks and benefits of participating in a clinical trial evaluating thalidomide or other promising therapies. Sources of information regarding ongoing clinical trials include comprehensive, easy-to-use listing services provided by the National Cancer Institute ( cancer.gov). ( Blood, Vol 98, No 4, pp 958-965, 2001)