Results recently published in the British Journal of Haematology suggest that thalidomide appears to be an effective treatment option for certain patients with myelodysplastic syndromes.

A myelodysplastic syndrome (MDS) 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 MDS, 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 MDS 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 MDS 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 MDS.

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 immunomodulatory 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 MDS is not entirely clear. Results from a previous clinical study have indicated that thalidomide may reduce the number of necessary blood transfusions and produce anti-cancer responses in MDS1, prompting further investigation into this treatment option for MDS.

European researchers recently conducted a clinical trial in which 30 MDS patients were treated with thalidomide for 12 weeks in escalating doses. Following treatment, 10 patients demonstrated significant hematological (blood/lymph) improvement, with increases in a variety of different blood cells and factors necessary for healthy, functioning blood. In addition, the bone marrow growth stimulant known as transforming growth factor beta (TGF-b), which tends to be higher in MDS patients than in healthy individuals, decreased after treatment with thalidomide. Six patients improved so greatly following treatment with thalidomide that they no longer required blood transfusions. The average time before an anti-cancer response to treatment was 10 weeks and four patients had no evidence of cancer one year following therapy. Researchers noted that patients who responded to treatment with thalidomide had significantly higher pre-therapy levels of platelets, bone marrow blasts and vascular endothelial growth factors (biochemicals that promote blood vessel growth) than did MDS patients that failed to improve with thalidomide.

Results from this recent clinical trial suggest that thalidomide is an effective treatment option for certain patients with MDS. Further research is needed to determine how thalidomide works, which patients will benefit most form thalidomide and to examine thalidomide alone or in combination with other treatment modalities within the context of a larger study for patients with MDS. Patients with MDS 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 ( ( British Journal of Haematology, Vol 115, No 4, pp 881-894, 2001)

  1. Blood, Vol 98, No 4, pp 958-965, 2001