The myelodysplastic syndromes (MDS) are a group of bone marrow disorders that present with various degrees of cytopenias to pancytopenia. Anemia is the most common presentation and the MCV may be variable; however, a macrocytic anemia with oval-shaped macrocytes is the more common presentation. The diagnosis should be strongly suspected in the presence of monocytosis, blood cytopenias/pancytopenia, a macrocytosis, and a peripheral smear with dysplastic cells. Thrombocytosis may be noted with MDS with isolated del(5q). There is a propensity to progress to acute myelogenous leukemia (AML). This is a disorder of the elderly with most patients being over 70 years of age, and males are affected more commonly than female patients. Primary disease occurs without any underlying history of chemotherapy, radiation therapy, or toxic exposure. Secondary disease from prior chemotherapy (alkylating agents, topoisomerase inhibitors, or podophyllotoxins), radiation therapy, or toxin exposure carries a worse prognosis. An increased incidence of MDS is associated with Down syndrome, Fanconi anemia, and Bloom syndrome.

Pancytopenia may be caused by many disease conditions. When there is associated splenomegaly, causes such as myeloproliferative disease, lymphoma, leukemia, and cirrhosis with portal hypertension should be considered. Splenomegaly is not associated with MDS and its presence should lead to a search for a different etiology. Pancytopenia without splenomegaly is characteristic of marrow failure and should raise suspicion for B12 deficiency, folate deficiency, copper deficiency, aplastic anemia, paroxysmal nocturnal hemoglobinuria (PNH), congenital bone marrow disorders, systemic lupus erythematosus, marrow infiltrative disorders (fungal infections, mycobacterial infections, metastatic cancers, etc) and infections to include HIV, Epstein-Barr virus, cytomegalovirus, and Parvovirus B-19.

The diagnosis should be considered when an elderly patient or one with a history of chemotherapy, radiation treatment, or toxin exposure presents with a cytopenia or pancytopenia without splenomegaly that cannot be attributed to aplastic anemia, vitamin/mineral deficiency (B12, folate, or copper deficiency), or an underlying disease state. MDS has few symptoms other than those attributed to the cytopenias such as fatigue, dyspnea, or chest pain (anemia), ecchymosis/bleeding (thrombocytopenia), or infections (leukopenia). The peripheral blood smear often demonstrates hypogranular neutrophils and pseudo-Pelger-Huet cells along with hypogranular platelets or undifferentiated blasts. Bone marrow aspirate and biopsy with staining and cytogenetic analysis is diagnostic by demonstrating dysplasia of erythroid precursors and megakaryocytes (nuclear budding or bridging along with megaloblastic red blood cell precursors or ringed sideroblasts and small mononuclear megakaryocytes) and the characteristic genetic variants. The World Health Organization (WHO) classification for the more common types of MDS includes: refractory anemia with unilineage cytopenia, refractory cytopenia with multilineage dysplasia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts-1 (5-9% blasts), refractory anemia with excess blasts-2 (10-19% blasts), myelodysplastic syndrome unclassified, and MDS with isolated del(5q).

Prognosis varies depending on whether the syndrome is primary (better prognosis) or secondary (worse prognosis). In primary disorders the prognosis varies depending on which type of MDS is present, which cytogenetic variant is detected, the severity of cytopenias, and the patient's age and comorbidities. Progression to AML and infections in neutropenic patients are the leading fatalities. The International Prognostic Scoring System (IPSS) uses the proportion of marrow myeloblasts, number of cytopenias, and type of chromosomal variant to determine prognosis. The chromosomal abnormalities are divided into poor risk (abnormalities of chromosome 7 or complex karyotypes with greater than three abnormal clones), good risk (normal karyotype, isolated deletion of the long arm of chromosome 5 aka del(5q), chromosome 20q deletions or loss of the Y chromosome), and intermediate risk (all others). -7/del(7q), del(5q), del(20q) and -Y are the more common chromosomal variants seen in primary MDS. Abnormalities of chromosome 5 or 7 account for approximately 75% of the karyotypes of secondary MDS.

Therapy entails symptomatic treatment of cytopenias such as erythropoietin or transfusions for anemia, platelet transfusions for bleeding, and C-CSF/GM-CSF to prevent infections in the presence of leukopenia. If the patient's erythropoietin level is greater than 500, transfusions will be required to treat the anemia. HLA antigen typing and screening for cytomegalovirus infection should be performed if hematopoietic stem cell transplantation is being considered as a form of therapy. As there are many forms of therapy with varying degrees of efficacy, consultation with a hematologist is prudent for therapeutic decision making. Agents used in therapy include immune suppression with antithymocyte globulin, azacitidine, decitabine, and lenalidomide.