The myelodysplastic syndromes (MDS) are a group of disorders characterized by one or more peripheral blood cytopenias secondary to bone marrow dysfunction. The MDS are diagnosed in slightly more than 10,000 people in the United States yearly for an annual age-adjusted incidence of 3.4/100,000 people.[1] The MDS are more common in men and whites. The syndromes may arise de novo, or secondarily after treatment with chemotherapy and/or radiation therapy for other diseases. Secondary myelodysplasia usually has a poorer prognosis than does de novo myelodysplasia. Prognosis is directly related to the number of bone marrow blast cells and to the amount of peripheral blood cytopenias. The MDS transform to acute myeloid leukemia (AML) in about 30% of patients after various intervals from diagnosis and at variable rates. (Refer to the Cellular Classification section for more information.)

The acute leukemic transformation is much less responsive to chemotherapy than is de novo AML. Prognosis is also related to the type of myelodysplastic syndrome. Supportive care has been the mainstay of treatment. Judicious use of platelet and blood transfusions and iron chelation may prevent or delay alloimmunization and iron overload and favorably affect prognosis.

The MDS are characterized by abnormal bone marrow and blood cell morphology. Megaloblastic erythroid hyperplasia with macrocytic anemia, which is associated with normal vitamin B₁₂ and folate levels, is frequently observed. Circulating granulocytes are frequently severely reduced, often hypogranular or hypergranular, and may display the acquired pseudo-Pelger-Huët abnormality. Early, abnormal myeloid progenitors are identified in the marrow in varying percentages, depending on the type of myelodysplastic syndrome. Abnormally small megakaryocytes (micromegakaryocytes) may be seen in the marrow and hypogranular or giant platelets may appear in the blood.

The MDS occur predominantly in older patients (usually >60 years), though patients as young as 2 years have been reported.[2] Anemia, bleeding, easy bruising, and fatigue are common initial findings. (Refer to the PDQ summary on Fatigue for more information.) Splenomegaly or hepatosplenomegaly may occasionally be present in association with an overlapping myeloproliferative disorder. Approximately 50% of the patients have a detectable cytogenetic abnormality, most commonly a deletion of all or part of chromosome 5 or 7, or trisomy 8.[3] Although the bone marrow is usually hypercellular at diagnosis, 15% to 20% of patients present with a hypoplastic bone marrow.[4] Hypoplastic myelodysplastic patients tend to have profound cytopenias and may respond more frequently to immunosuppressive therapy.

A variety of risk classification systems have been developed to predict the overall survival of patients with MDS and the evolution from MDS to AML. These classification systems include the French-American-British classification,[5] the Bournemouth score,[6] the Sanz score,[7] the Lille score,[8] and the World Health Organization classification.[9] Clinical variables in these systems have included bone marrow and blood myeloblast percentage, specific cytopenias, age, lactate dehydrogenase level, and bone marrow cytogenetic pattern.

An International MDS Risk Analysis Workshop was convened, and the clinical data from 816 patients with primary MDS from seven previously reported studies, which used independent risk-based prognostic systems, were combined and collated.[10] The combined data were analyzed centrally, and a global analysis was performed, which formed the basis of a new prognostic system called the International Prognostic Scoring System for MDS.[10] In multivariate analyses, significant predictors for both survival and AML evolution included bone marrow blast percentage, number of peripheral blood cytopenias, and cytogenetic subgroup. The data are used to assign MDS patients a score, which stratifies patients into one of four risk groups: low risk, intermediate-1, intermediate-2, and high risk. The time for the development of AML in the risk groups was 9.4 years, 3.3 years, 1.1 years, and 0.2 years, respectively. Median survival for the groups was 5.7 years, 3.5 years, 1.2 years, and 0.4 years, respectively. The system has been incorporated into clinical trial design for MDS.

References

1. Ma X, Does M, Raza A, et al.: Myelodysplastic syndromes: incidence and survival in the United States. Cancer 109 (8): 1536-42, 2007.  [PUBMED Abstract]
   
   
2. Tuncer MA, Pagliuca A, Hicsonmez G, et al.: Primary myelodysplastic syndrome in children: the clinical experience in 33 cases. Br J Haematol 82 (2): 347-53, 1992.  [PUBMED Abstract]
   
   
3. Gyger M, Infante-Rivard C, D'Angelo G, et al.: Prognostic value of clonal chromosomal abnormalities in patients with primary myelodysplastic syndromes. Am J Hematol 28 (1): 13-20, 1988.  [PUBMED Abstract]
   
   
4. Nand S, Godwin JE: Hypoplastic myelodysplastic syndrome. Cancer 62 (5): 958-64, 1988.  [PUBMED Abstract]
   
   
5. Bennett JM, Catovsky D, Daniel MT, et al.: Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 51 (2): 189-99, 1982.  [PUBMED Abstract]
   
   
6. Mufti GJ, Stevens JR, Oscier DG, et al.: Myelodysplastic syndromes: a scoring system with prognostic significance. Br J Haematol 59 (3): 425-33, 1985.  [PUBMED Abstract]
   
   
7. Sanz GF, Sanz MA, Vallespí T, et al.: Two regression models and a scoring system for predicting survival and planning treatment in myelodysplastic syndromes: a multivariate analysis of prognostic factors in 370 patients. Blood 74 (1): 395-408, 1989.  [PUBMED Abstract]
   
   
8. Aul C, Gattermann N, Heyll A, et al.: Primary myelodysplastic syndromes: analysis of prognostic factors in 235 patients and proposals for an improved scoring system. Leukemia 6 (1): 52-9, 1992.  [PUBMED Abstract]
   
   
9. Brunning RD, Bennett JM, Flandrin G, et al.: Myelodysplastic syndromes. In: Jaffe ES, Harris NL, Stein H, et al., eds.: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press, 2001. World Health Organization Classification of Tumours, 3, pp 61-73. 
   
   
10. Greenberg P, Cox C, LeBeau MM, et al.: International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 89 (6): 2079-88, 1997.  [PUBMED Abstract]
    
    

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