The Myelodysplastic Syndromes

Review for patients, families, friends and health professionals


  1. To define the myelodysplastic syndromes (MDS)
  2. To delineate the differences between aplastic anemia (AA) , acute myeloid leukemia (AML), and MDS
  3. To discuss the relationship between MDS and AA at disease presentation and subsequent to successful treatment of AA


The myelodysplastic syndromes are a group of bone marrow neoplastic diseases that share many of the morphologic features of the acute myeloid leukemias with some important differences. First, the percentage of undifferentiated progenitor cells ("blasts") is always less than 30% and there is considerably more dysplasia (special morphologic changes in the nuclei and cytoplasm of the red blood cell precursors, granulocytic precursors and megakaryocytic precursors) than what is usually seen in cases of AML. These changes represent a type of delayed apoptosis or a failure of programmed cell death.

As a result, the bone marrow preparations when examined either directly from the aspirate or from a biopsy are quite cellular to hypercellular after correction for the age of the patient. This age correction is very important, since over 90% of cases of MDS occur in individuals over 60 years of age, where the normal cellularity has already been reduced to 50% of normal (25% by 80 years of age).

The likelihood of progression to AML varies with the subtype of MDS. It can range from less than 10% to as high as 50%, with an overall rate of transformation of 30%.

Patients present with either refractory anemia, granulocyto-penia, thrombocytopenia or a combination of these deficiencies. If not corrected, death can result without progression to AML but the median survival is considerably longer than untreated AML, with most patients living for several to many years.


Considerable evidence has been developed implicating the multi-potential stem cell that is capable of both myeloid and lymphoid differ-entiation and to demonstrate that this is a clonal disease. Cytogenetic abnormalities are common and occur in about 60% of cases. The chromosomal changes can be recognized in patients with AML as well, further evidence linking these diseases.

Familial occurrence has been reported as well as a high incidence in patients affected with Down’s Syndrome, Fanconi’s anemia, and neurofibromatosis.

Occupational/environmental exposure may increase risk but, to date benzene is the only chemical that has been linked to MDS. Smoking and accidental exposure to massive doses of radiation are also risk factors.

Iatrogenic (therapy related to MDS) factors include chemotherapy given for curative effect for patients with a variety of malignancies (leukemias, lymphomas, testicular, breast, colon, ovarian cancers, etc) can result in the development of an MDS/AML syndrome in about 2% of cured patients. Two types of leukemia have been described, associated with different chromosomal changes.

Approximately 10,000 cases of MDS are diagnosed in the United States each year, of which 10% can be attributed to known or suspected carcinogens.


MDS can be classified into five subgroups. The basis for the groupings rests on calculating the % of bone marrow blasts, the amount of iron in the red blood cell precursors ("ringed sideroblasts"), and whether there are increased numbers of monocytes in the peripheral blood smear. Patients who have less than 5% blasts tend to have a better prognosis, with a median survival of 4-5 years. Patients who have 5-10% blasts have a median survival of about 2 years and those with 10-30% blasts survive for about 1 year, if they do not receive aggressive therapy. One of the subtypes, chronic myelo-monocytic leukemia, shares features of both MDS and the myelo-proliferative disorders such as chronic granulocytic leukemia.


The therapy of patients with MDS is highly individualized. Many patients can be observed without intervention or with occasional red blood cell transfusions or a trial of erythropoietin, a red blood cell stimulating agent. Platelet transfusions may be of limited benefit, and other growth factors, including G-CSF, GM-CSF, IL-3, IL-6, and IL-II are under investigation. For selected patients intensive chemotherapy, similar to what is utilized in AML, may produce short-term remissions in about 40% of patients. Allogeneic BMT has been successful in young patients, under age 40, with long-term remissions or cure in 40-50% of the cases.


MDS is often a diagnosis of exclusion after ruling out other disorders associated with low blood counts. These include vitamin B12 and/or folic acid deficiency, heavy metal poisoning (such as arsenic), or certain viral infections including acute parvo virus B19 and Epstein-Barr virus (EBV). When there is an obvious increase in blast cells and dysplastic features and a normal to hypercellular marrow, the diagnosis is not difficult but must be distinguished from the acute myeloid leukemias.

Since 15-20% of patients with MDS present with a hypocellular marrow (usually below 30% cellularity), there are some difficulties in separating these cases from patients with aplastic anemia. A careful search for the morphologic characteristics will almost always establish the distinction between these two entities and also from the very rare form of hypo-cellular AML. In our own experience this represents 15% of our AMLs. Although "clonal hematopoiesis" is strongly suggestive of MDS or AML, sophisticated studies in patients with aplastic anemia have been "informative" in as high as 90% of women, as determined by restriction fragment length polymorphism (RFLP) of x-linked gene, phosphoglycerate kinase, HPRT, of the x-linked probe M27 beta. Usually, however, there are no chromosomal abnormalities found. In the rare instance where a chromosomal change is discovered with all of the other features of aplastic anemia, conventional treatment for AA should be offered.

Unfortunately, for those who are "cured" of their aplastic anemia with hormones, ATG, or ALLOBMT, a significant minority, will develop either MDS or PNH over several years. Some studies suggest that this is less likely to occur in the recipients of BMT.


The future for the better understanding and management of MDS is optimistic. Scientists from all over the world have joined together to review and to present their findings in an international format that meets every 2 years. Through this forum of an MDS newsletter, and a "web" page devoted to MDS, we hope to provide current and pertinent information to physicians and their patients and family members.

John M. Bennett, MD, University of Rochester Cancer Center, Rochester, New York USA