Anti-Inflammatory Drug Combination Appears to Improve Blood Counts for Persons
A myelodysplastic syndrome is a disease of the bone marrow that eventually progresses into leukemia, a type of cancer. While 1 curative option for myelodysplastic syndrome is a procedure called a stem cell transplantation, not all persons are able to tolerate the potentially life-threatening complications that can occur with this procedure. For these persons, biologic agents and chemotherapy drugs are used to help the bone marrow produce more normal blood cells, relieve the signs and symptoms of disease, and prolong survival time. Now, researchers say that a combination of pentoxifylline, ciprofloxacin, amifostine, and dexamethasone appears to be an effective new treatment option for improving blood cell counts.
A myelodysplastic syndrome is a disease in which the cells in a person’s bone marrow are not functioning normally. This condition is sometimes referred to as a pre-leukemia or “smoldering” leukemia, because it usually develops into leukemia, which is a type of cancer. 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 (protect the body from infection), red blood cells (carry oxygen to the tissues), and platelets (help the blood to clot). In the case of myelodysplastic syndromes, not enough normal blood cells are being produced in the marrow. One theory is that cells, called inflammatory cytokines, are produced uncontrollably and kill the normal cells in the bone marrow. There are many types of myelodysplastic syndromes, many of which are referred to as different types of anemias. The term anemia is used to describe the deficiency in red blood cells that results in some persons with myelodysplastic syndrome.
Other than stem cell transplantation, treatment of myelodysplastic syndrome often consists of the infusion of red blood cells or platelets to compensate for the inadequate production of these cells in the bone marrow. Biologic agents, such as Neupogen and erythropoietin, are also used to help white and red blood cells to grow more rapidly. One new treatment approach is the use of inflammatory cytokine suppressants, which inhibit the production of inflammatory cytokines. Researchers used 2 such drugs, pentoxifylline and dexamethasone, to treat persons with myelodysplastic syndrome. They also combined these agents with 2 helper drugs, ciprofloxacin to enhance the level of pentoxifylline in the blood and Ethyol® to protect healthy cells and further enhance blood cell counts.
Researchers at the Rush Cancer Institute treated 35 persons with myelodysplastic syndrome. The types of myelodysplastic syndrome treated included refractory anemia, refractory anemia with sideroblasts, refractory anemia with excess blasts, chronic myelomonocytic leukemia, and myelodysplasia from previous drug treatment. Each person received pentoxifylline, ciprofloxacin, and amifostine; patients who did not respond or who responded only partially to this therapy also received dexamethasone. The results showed that 22 persons responded to this treatment strategy with an improvement in white blood cell, red blood cell, and/or platelet counts. Nineteen had an improvement in white blood cell count, 11 had an improvement in hemoglobin (an iron-rich protein on red blood cells) levels and/or a 50% reduction in the number of blood transfusions required; and 7 had an improvement in platelet count. These responses occurred slowly, with improvements continuing up to 1 year after the treatment began. There were no significant side effects, except for nausea and vomiting.
These findings suggest that pentoxifylline, ciprofloxacin, and amifostine, either with or without dexamethasone, is an effective and safe combination for achieving improved blood cell counts in persons with myelodysplastic syndrome. Persons who have myelodysplastic syndrome may wish to talk with their doctor about the risks and benefits of the pentoxifylline/ciprofloxacin/amifostine/dexamethasone regimen, or of participating in a clinical trial in which other new treatments are being studied. Sources of information on ongoing clinical trials that can be discussed with a doctor include a comprehensive, easy-to-use service provided by the National Cancer Institute ( cancer.gov). ( Blood, Vol 95, No 5, pp 1580-1587, 2000).