Treatment options are predicated on specific abnormalities and prognostic category (see “Risk Categories” section below).
The same treatment options are available for patients in any subtype of myelodysplasia depending on morbid manifestations.
The main considerations in all subtypes are (1) severity of anemia (demethylating agents, erythropoietic stimulants), (2) severity of neutropenia and infections (antibiotics), (3) severity of thrombocytopenia and evidence of bleeding (platelet transfusion), (4) special case of hypoplastic marrow (immunosuppressive therapy), and (5) evidence of progressive leukemic hematopoiesis (blast level) requiring acute leukemia type cytotoxic therapy or allogeneic hematopoietic stem cell transplantation. See following details.
Asymptomatic patients without evidence of progression may not require treatment.
Disorder may not progress for many years.
Folic acid (1 mg/d orally) should be used if serum and red cell folic acid content are low.
Pyridoxine (200 mg/d orally) can be tried if sideroblastic anemia is symptomatic, but success is rare.
Danazol (200 to 400 mg/d orally) has occasionally increased platelet count or decreased frequency of platelet transfusion.
In uncommon patients with clonal cytopenia and hypoplastic marrows, cyclosporine and antithymocyte globulin have resulted in improvement in hematopoiesis (see Chap. 3).
Human recombinant erythropoietin (EPO) coupled with granulocyte colony-stimulating factor (G-CSF) may improve moderately severe anemia or may markedly decrease transfusion requirements. This combination is usually not beneficial unless (1) the serum EPO level is less than 500 units/L and (2) the transfusion requirement is less than 2 units of red cells per month.
5-Azacytidine, 75 mg/m2 per day, subcutaneously (or intravenously) for 7 days every 28 days can be useful in patients with symptomatic anemia and requirement for frequent transfusions. About 40% of patients have a very good response as judged by the increase in hemoglobin levels or a significant decrease in transfusion frequency. Heretofore, the drug was used in patients failing to respond to EPO and G-CSF but evidence that its use may delay progression of the disease and prolong survival in responders is likely to make it a first choice in such patients, administered before the results of EPO + G-CSF are evident. Although 5-azacytidine is an antimetabolite, its benefit is thought to be related principally to its demethylating effects (reversing deleterious epigenetic effects).
5-Azacytidine may initially cause a fall in blood cell counts, even in responders, and transfusion requirements may increase during the first one to several weeks of therapy. It may take four to five cycles of therapy to achieve a response and maximum responses may not occur for nine to ten cycles.
Decitabine, another cytotoxic agent with demethylating effects, has been approved for use in lieu of 5-azacytadine. One regimen proposed is 20 mg/m2 intravenously over 1 hour daily for 5 days to be repeated every 4 weeks for a total of three cycles. Worsening of cytopenias may occur initially, but some experts recommend that unless a complication of cytopenia develops or other serious side effects occur, the treatment program should not be modified.
Red cell transfusion may be necessary if severe anemia or if coincidental ischemic diseases (eg, angina or heart failure) are present with moderate anemia.
Some patients with high red cell transfusion requirements develop iron overload and should receive iron chelation therapy. Oral deferasirox, 20 mg/kg per day, has been approved by the US Food and Drug Administration for this purpose. It can produce nausea, vomiting, abdominal pain, skin rash, and other adverse effects (see Chap. 9).
One guideline for use of iron chelator therapy requires three criteria to be met: (1) probable survival for at least 1 year, (2) receipt of more than 20 units of red cells, and (3) a serum ferritin of greater than 1000 μg/L.
Some patients do not progress or may live for many years before progression occurs. Others may have worsening hematopoiesis, more severe cytopenias, and morbidity and mortality from recurrent severe infections or hemorrhage.
On average, a normal or only slightly abnormal neutrophil and platelet count suggests a better prognosis. A mild anemia not requiring transfusions also portends a better outcome on average.
About 10% of patients progress to AML over a 10-year period of observation.
Median survival is about 7 to 9 years in different studies.