Myelodysplastic Syndromes and Aplastic Anemia Pathologic and Immunologic Implications

John M. Bennett

The Myelodysplastic Syndromes (MDS) represent a heterogeneous group of bone marrow diseases of uncertain etiology characterized by a variable degree of cytopenias, predominantly but not exclusively anemia that is often macrocytic (1). The cytopenias reflect both ineffective hematopoiesis (marrow dysplasia or accelerated apoptosis) and increase in marrow leukemic blasts (2). In 85% of cases the marrow is normo to hypercellular but in 15% the marrow cellularity can be below 30% and, on occasion, below 15%, which raises the differential diagnosis with acquired aplastic anemia (3). In such instances it is necessary to depend on the morphologic identification of significant dysplasia of one or more of the myeloid cell lines or the identification of small clusters of blasts on a bone marrow biopsy. Over 50% of all cases occur in patients over the age of 70 years. Each year some 15,000 individuals will be diagnosed with MDS, although this may well be an underestimate. In a recent national survey of elderly patients with anemia (4) some 17% met the criteria for unexplained anemia and leucopenia or thrombocytopenia. This would amount to a prevalence of 163,000 individuals who might have MDS with a more careful evaluation.

Approximately 50% of patients have acquired chromosomal aberrations. The most common include; +8; del5q; -7 and 20q- (5). The median survival is about 3 years but can range from less than 6 months to over 10 years. Thirty percentage will progress to Acute Myeloid Leukemia. This is much more common when the initial percentage of blasts exceeds 5% compared to less than 5% blasts. Therefore, close to 70% of patients will suffer from complications of cytopenias without disease progression to AML. For these latter patients effective treatment of the marrow failure without the use of cytotoxic drugs should offer a more desired form of treatment, without the complications of chemotherapy.

There is strong evidence that in some cases MDS is the result of an intrinsic, presumably acquired, genetic defect in hematopoietic stem cells.

However, other patients clearly have an autoimmune basis for their disease, since clinically MDS may be associated with other autoimmune disorders and laboratory evidence has documented oligoclonal t-cell patterns in upwards of 50% of patients tested (6).

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