MYELODYSPLASTIC SYNDROMES (MDS)
The MDSs are a group of disorders of the myeloid stem cell that cause dysplasia (abnormal development) in one or more types of cell lines. The most common feature of MDS—dysplasia of the RBCs—is manifested as a macrocytic anemia; however, the WBCs (myeloid cells, particularly neutrophils) and platelets can also be affected. Although the bone marrow is actually hypercel-lular, many of the cells within it die before being released into the circulation. Therefore, the number of affected cells in the circula-tion is typically lower than normal. In addition to the quantitative defect (ie, fewer cells than normal), there is also a qualitative de-fect: the cells are not as functional as normal. The neutrophils have diminished ability to destroy bacteria by phagocytosis; platelets are less able to aggregate and are less adhesive than usual. The result of these qualitative defects is an increased risk for infection and bleeding, even when the actual number of circulating cells may not be excessively low. A significant proportion of MDS cases evolve into acute myeloid leukemia (AML); this type of leukemia tends to be nonresponsive to standard therapy.
Primary MDS tends to be a disease of the elderly; more than 80% of patients with MDS are older than 60 years of age. Sec-ondary MDS may occur at any age and results from prior toxic exposure to chemicals, including chemotherapeutic medications (particularly alkylating agents). Secondary MDS tends to have a poorer prognosis than does primary MDS.
The manifestations of MDS can vary widely. Many patients are asymptomatic, with the illness being discovered incidentally when a CBC is performed for other purposes. Other patients have profound symptoms and complications from the illness. Fa-tigue is often present, at varying levels. Neutrophil dysfunction renders the person at risk for infection; recurrent pneumonias are not uncommon. Because platelet function can also be altered, bleeding can occur. These problems may persist in a fairly steady state for months, even years. They may also progress over time; as the dysplasia evolves into a leukemic state, the complications increase in severity.
The CBC typically reveals a macrocytic anemia; WBC and platelet counts may be diminished as well. Serum erythropoietin levels may be inappropriately low, as is the reticulocyte count. As the disease evolves into AML, more immature blast cells are noted on the CBC.
With the exception of allogeneic bone marrow transplantation (BMT), there is no known cure for MDS. Chemotherapy has been used, particularly in patients with more aggressive forms of the illness, typically with disappointing results (Deeg & Applebaum, 2000; Beran, 2000). However, patients with mild cytopenias (low blood counts) actually require no therapy. For most patients with MDS, transfusions of RBCs are required to control the anemia and its symptoms. These patients can develop signif-icant problems with iron overload from the repeated transfusions; this problem can be diminished with prompt initiation of chela-tion therapy to remove the excess iron (see Nursing Management). In some patients, the use of erythropoietin can be successful in reducing the need for transfusions and their attendant complica-tions. Some patients may also require ongoing platelet transfusions to prevent significant bleeding. Infections need to be managed aggressively and promptly. Administration of growth factors, par-ticularly granulocyte colony-stimulating factor (G-CSF), eryth-ropoietin, or both, has been successful in increasing neutrophils and diminishing anemia in certain patients; however, these agents are expensive and the effect is lost if the medications are stopped. Because MDS tend to occur in elderly people, other chronic con-ditions may limit treatment options. Secondary MDS and MDS that evolves into AML tend to be much more refractory to con-ventional therapy for leukemia.
Caring for patients with MDS can be challenging because the ill-ness is unpredictable. As with other hematologic conditions, some patients (especially those with no symptoms) have difficulty per-ceiving that they have a serious illness that can place them at risk for life-threatening complications. At the other extreme, many pa-tients have tremendous difficulty coping with the uncertain trajec-tory of the illness and fear that the illness will evolve into AML at a time when they are feeling very well physically.
Patients with MDS need extensive instruction about infection risk, measures to avoid it, signs and symptoms of developing in-fection, and appropriate actions to initiate should such symptoms occur. Instruction should also be given regarding the risk for bleeding. Patients with MDS who are hospitalized may require neutropenic precautions.
Laboratory values need to be monitored closely to anticipate the need for transfusion and to determine response to treatment with growth factors. Patients with chronic transfusion require-ments usually benefit from a vascular access device for this pur-pose. Patients receiving growth factors or chelation therapy must be educated about these medications, their side effects, and ad-ministration techniques.
Chelation therapy is a process that is used to remove excess iron acquired from chronic transfusions. Iron is bound to a sub-stance, the chelating agent, and then excreted in the urine. Oral forms of chelating agents have not been successful (due to either diminished efficacy or excessive toxicity). Chelation therapy is most effective as a subcutaneous infusion administered over 8 to 12 hours; most patients prefer to do this at night. Because chela-tion therapy removes only a small amount of iron with each treat-ment, patients with chronic transfusion requirements (and iron overload) need to continue chelation therapy as long as the iron overload exists, potentially for the rest of their lives. Patients who are embarking on chelation therapy must be highly motivated and need instruction in the subcutaneous infusion technique, in-fusion pump maintenance, and side effect management. Local erythema at the injection site is the most common reaction and typically requires no intervention. Patients should have baseline and annual auditory and eye examinations, because hearing loss and visual changes can occur with treatment.