Progression to an acute leukemia is always a concern for patients with an MDS. Low-grade disorders like RA or RARS have longer survival times and less tendency to develop into overt acute leukemias. These disorders are also unilineage. Disorders, however, like RAEB and the multilineage disorders are high grade with much shorter survival times and a greater incidence to progress to acute leukemia. Other factors such as multiple cytogenetic abnormalities, especially chromosome 7 abnormalities, have an unfavorable predictive influence (Table 14.3). Treatment of the MDS is difficult to manage. Issues such as quality of life, severe thrombocy-topenia, and progression to more advanced disease are serious concerns. Patients with MDSs are classified into low- or high-risk categories based on their initial WHO
Table 14.3 O Factors Indicating
Progression to Leukemia in MDS
• Disease is stable if there is little increase in marrow blast count and the original karyotype is unchanged.
• Progressive rise in blast count usually indicates transition to acute leukemia.
• Sudden change in karyotype that may progress into acute leukemia.
• Abnormal karyotype develops without subsequent increase in blasts; acute leukemia may or may not develop.
Adapted from Bick RL, Laughlin WR. Myelodysplastic syndromes.
Lab Med 11:712-716, 1993.
designation. Treatment protocols tailored to these designations range from transfusional support to erythropoietin (EPO) and G-CSF (granulocyte-colony stimulating factor), induction chemotherapy, and allo-geneic stem cell transplant. Although stem cell transplants offer a potential cure, the morbidity and mortality associated with this procedure must be seriously considered.8 Even in patients with allogeneic transplants there has only been a 30% to 50% long-term disease control.9 Most patients are given supportive treatment such as red cells, antibiotics, or vitamins. The difficulty with this management is that the anemias are refractory, necessitating more transfusions, which may lead to iron overload. Iron chelating agents may be used but are more successful in younger patients. Recall that individuals with iron overload are usually attached to an iron chelating pump, which works to clear their blood of excess iron while they sleep. Generally, younger patients are more compliant than older individuals and are better able to cope with the constancy of this procedure. Oral iron chelators such as deferiprone and IL 670 will likely improve iron chelation therapy in this patient group.10 Patients with cardiopulmonary complications due to progressive anemia must be handled carefully. EPO and G-CSF are important supplementary agents, and they are effective short-term measures during difficult episodes of cytopenias.11 Several immunobiologic therapies are being considered in clinical trials such as anti-thymocyte globulin, anti-CD33 antibody, idarubicin, and fludarabine.12 Additionally, a group of therapies known as antiangiogenic therapies are on the horizon. These agents direct their activities against microenvironmental factors such as vascular endothelial growth factor (VEGF) and tumor necrosis factor. It is thought that the increased production of these inflammatory factors amplify ineffective hematopoiesis, fuel the growth of certain premalignant or malignant cells, and suppress normal hematopoietic progenitor cells. Thalidomide (lenalidomide) and arsenic trioxide have both been studied.13 Therapies for MDS will no doubt improve as the disease mechanisms become more clearly defined.
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