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First recognized as separate diagnoses in 1976 [15], the myelodysplastic syndromes (MDS) comprise a heterogeneous group of closely related disorders that disrupt the production of one or more blood cell types. Myelodysplastic syndromes are difficult to treat, because they present the unusual combination of hyperactive bone marrow and defective erythropoiesis. Premature red blood cell apoptosis often leads to progressive cytopenia. This contrasts with leukemia, in which there is proliferation of white blood cells, but other cell types are unaffected.
According to the World Health Organization (WHO) classification system [16], MDS can be grouped into one of eight types, each with differing disease progression and survival rate. Significant differences have been observed in the survival rates of these different types [17], hence classification at an early stage can prove essential for prognosis. There are also rarer types of MDS that may also have significant clinical effects, including refractory dysmyelopoietic anemia, smoldering acute leukemia, smoldering leukemia and subacute myelogenous leukemia.
| Disease |
Blood findings |
Bone marrow findings |
Proportion of MDS patients, % |
Survival |
| Refractory anemia (RA) |
Anemia
No or rare blasts |
Erythroid dysplasia only
<5% blasts
<15% ringed sideroblasts |
5-10 |
Median survival of 63-108 months |
| RA with ringed sideroblasts (RARS) |
Anemia
No blasts |
Erythroid dysplasia only
≥15% ringed sideroblasts
<5% blasts |
10-15 |
Median survival of 69-108 months |
| Refractory cytopenia with multilineage dysplasia (RCMD) |
Cytopenias (bicytopenia or pancytopenia)
No or rare blasts
No Auer rods <1×109/L monocytes |
Dysplasia in ≥10% of cells in two or more myeloid cell lines
<5% blasts in bone marrow
No Auer rods
<15% ringed sideroblasts |
24 |
Median survival of 24-49 months and a 4-year survival rate of 48% (+/- 13%) |
| RCMD and ringed sideroblasts (RCMD-RS) |
Cytopenias (bicytopenia or pancytopenia)
No or rare blasts
No Auer rods <1×109/L monocytes |
Dysplasia in ≥10% of cells in two or more myeloid cell lines
≥ 15% ringed sideroblasts <5% blasts No Auer rods |
0-15 |
Median survival of 24-32 months and a 4-year survival rate of 48% (+/- 13%) |
| RA with excess blasts-1 (RAEB-1) |
Cytopenias
<5% blasts
No Auer rods
<1×109/L monocytes |
Unilineage or multilineage dysplasia 5-9% blasts No Auer rods |
20 |
Median survival of 12-18 months |
| RA with excess blasts-2 (RAEB-2) |
Cytopenias
5-19% blasts
Auer rods +/-
<1×109/L monocytes |
Unilineage or multilineage
dysplasia
10-19% blasts
Auer rods +/- |
20 |
Median survival is 6-10 months, but can be increased with chemotherapy |
| MDS, unclassified (MDS-U) |
Cytopenias
No or rare blasts
No Auer rods |
Unilineage dysplasia in
granulocytes or
megakaryocytes
<5% blasts
No Auer rods |
Variable |
Disease progression difficult to predict |
| MDS associated with isolated del (5q) |
Anemia
<5% blasts
Platelets normal or increased |
Normal to increased megakaryocytes with hypolobulated nuclei <5% blasts No Auer rods Isolated del (5q) |
<5 |
Median survival of 116 months |
Overall survival of MDS patients according to the WHO criteria (P<0.001) [16;17] Reprinted with permission from the American Society of Clinical Oncology. Malcovati L et al: J Clin Oncol 23 (30), 2005: 7594-7603.
AML=acute myeloid leukemia
Myelodysplastic syndromes are most common in older adults, with a median onset in the seventh decade of life [21]. They may be caused by a variety of medical, environmental, and hereditary factors including chemotherapy [22], radiation [23], toxic chemical exposure [24], viral infection [25], or genetic predisposition [26]. MDS causes major changes in peripheral blood counts and morphology, as well as bone marrow abnormalities. Morbidity and mortality result from anemia, bleeding and infection.
Bone-marrow transplantation can cure MDS, but is prohibitively toxic in older patients. Due to the major decrease in red blood cell production, the main goals of transfusion therapy for MDS are to increase hemoglobin counts, to alleviate symptoms (e.g. so that patients are less fatigued and able to maintain their independence), and, possibly, to extend survival. Due to the variable nature of symptoms and disease progression, the type of MDS must be established before identifying the appropriate transfusion regimen. In addition, the age of the patient must be taken into consideration. Approximately 80-90% of MDS patients will receive a blood transfusion at some point in their life as they are essential to improve quality of life and, in some patients, survival [27]. However, the potential negatives of transfusion therapy that must be considered include transmission of infection, adverse effects attributable to immune mechanisms, and, most importantly, iron overload. It has been shown that iron overload can significantly reduce survival in MDS, with a 30% increase in hazard ratio for every 500 ng/mL increase in serum ferritin levels above a threshold of 1000 ng/mL [17]. Cardiac death is also significantly more common in patients who are transfusion dependent than those who are not.
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