According to results recently published in the journal Blood, the treatment combination of all-trans retinoic acid plus erythropoietin appears to be an effective and well tolerated treatment option for 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 may be associated with cost, discomfort, inconvenience, infection and rejection of donor cells. Researchers are investigating novel therapies for patients with MDS.
Erythropoietin (EPO) is a substance normally produced by the kidneys that stimulates the bone marrow to produce and mature red blood cells. Several trials have shown an approximate 20% response rate in patients with MDS treated with EPO that has been produced in a laboratory. In addition, studies have indicated that the chemotherapeutic agent all-trans retinoic acid (ATRA) reacts with EPO in a way that augments the production of blood cells.
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Researchers from Italy recently conducted a clinical trial evaluating ATRA plus EPO in 27 patients with MDS who were at a low or intermediate risk of developing leukemia. Following treatment, almost half of the patients had increased levels of hemoglobin (a component of red blood cells) and/or a reduction in transfusion needs. During the six months of treatment, 37% of patients had continuous responses and 26% of patients are still responsive at 13 months of treatment. White blood cell levels were improved in five of 12 patients with neutropenia (low levels of white blood cells) and platelets levels were improved in six of nine patients with thrombocytopenia (low levels of platelets). Three patients displayed improved levels of all three types of blood cells which were sustained during treatment. Side effects were mild and did not require dose reductions, but occurred in all patients.
These authors concluded that ATRA plus EPO is an effective and well tolerated therapy for patients with low to intermediate risk MDS. However, the optimal ATRA and EPO treatment schedule and role of treatment in MDS remain to be determined through further evaluation. Patients with MDS may wish to speak with their physician about the risks and benefits of participation in a clinical trial further evaluating ATRA plus EPO or other novel therapeutic approaches. Two sources of information regarding ongoing clinical trials include the National Cancer Institute (cancer.gov) and www.eCancerTrials.com. eCancerTrials.com also provides personalized clinical trial searches on behalf of patients. (Stasi R, Brunetti M, Terzoli E, et al: Sustained response to recombinant human erythropoietin and intermittent all-trans retinoic acid in patients with myelodysplastic syndromes. Blood 2002; 99: 1578-1584)
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