Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 13-28: Myelodysplastic Syndromes + Key Features Download Section PDF Listen +++ +++ Essentials of Diagnosis ++ Cytopenias with hypercellular bone marrow Morphologic abnormalities in one or more hematopoietic cell lines +++ General Considerations ++ Group of acquired clonal disorders of the hematopoietic stem cell, characterized by the constellation of cytopenias, a usually hypercellular marrow, morphologic dysplasia and genetic abnormalities Causes Idiopathic (most common) Prior exposure to cytotoxic chemotherapy or radiation therapy In addition to cytogenetics, sequencing can detect genetic mutations in 80–90% of patients Acquired clonal mutations identical to those seen in myelodysplastic syndrome can occur in the hematopoietic cells of ~10% of apparently healthy older individuals, defining the disorder of clonal hematopoiesis of indeterminate potential (CHIP) Myelodysplasia encompasses several heterogeneous syndromes; a key distinction is whether there is an increase in bone marrow blasts (> 5% of marrow elements) MDS with excess blasts represents a more aggressive form of the disease, often leading to acute myeloid leukemia Patients without excess blasts are characterized by the degree of dysplasia, eg, MDS with single lineage dysplasia and MDS with multilineage dysplasia The morphologic finding of MDS with ringed sideroblasts is used to define a subcategory of lower risk syndromes Patients with isolated 5q loss, which is characterized by the cytogenetic finding of loss of part of the long arm of chromosome 5, comprise an important subgroup of patients with a different natural history Chronic myelomonocytic leukemia (CMML) is a proliferative syndrome, including sustained peripheral blood monocytosis > 1000/mcL (> 1.0 × 109/L) +++ Demographics ++ Occurs most often in patients aged > 60 + Clinical Findings Download Section PDF Listen +++ +++ Symptoms and Signs ++ Asymptomatic, with incidentally found cytopenias Symptoms and signs are related to bone marrow failure Symptoms Fatigue Bleeding Signs Fever Infection Wasting Weight loss Splenomegaly Pallor Paraneoplastic syndromes of various sorts (prior to or following diagnosis) +++ Differential Diagnosis ++ Acute myeloid leukemia (AML) (≤ 20% blasts) Aplastic anemia Anemia of chronic disease Vitamin B12 or folate deficiency Megaloblastic anemia Myelofibrosis HIV-associated cytopenias Acute or chronic drug effect + Diagnosis Download Section PDF Listen +++ +++ Laboratory Tests ++ Anemia may be marked Mean cell volume is normal or increased Peripheral blood smear may show macro-ovalocytes White blood cell count usually normal or reduced; neutropenia is common Neutrophils may exhibit morphologic abnormalities, including deficient numbers of granules, or bilobed nucleus (Pelger-Huet abnormality) Myeloid series may be left shifted with small numbers of promyelocytes or blasts Platelet count is normal or reduced; hypogranular platelets may be present +++ Diagnostic Procedures ++ Bone marrow aspirate and biopsy are characteristically hypercellular (but may occasionally be hypocellular) Signs of abnormal erythropoiesis include Megaloblastic features Nuclear budding Multinucleated erythroid precursors Prussian blue stain may demonstrate ringed sideroblasts Myeloid series is often left shifted with variable increases in blasts Deficient or abnormal myeloid granules may be seen A characteristic abnormality is dwarf megakaryocytes with unilobed nucleus Cytogenetics may be abnormal No specific chromosomal abnormality is seen, but abnormalities in chromosomes 5 and 7 are common + Treatment Download Section PDF Listen +++ +++ Medications ++ For patients with anemia who have a low serum erythropoietin level (≤ 500 milli-units/mL), erythropoiesis-stimulating agents (epoetin alfa, darbepoetin) may Raise the hematocrit Reduce red blood cell transfusion requirement Addition of intermittent granulocyte colony stimulating factor (G-CSF) therapy may augment the erythroid response to epoetin or darbepoetin Oral deferasirox (20 mg/kg/day in divided dosing) Used as iron chelation therapy Prevents serious iron overload in patients who do not have immediately life-threatening disease but who depend on periodic red blood cell transfusions Lenalidomide Recommended initial dose is 10 mg orally daily Approved for treatment of transfusion-dependent anemia due to myelodysplasia Treatment of choice in patients with MDS with isolated del(5q) Most common side effects are neutropenia and thrombocytopenia, but venous thrombosis is also seen and warrants aspirin prophylaxis (325 mg/day orally) Cost is extremely high, and it is not effective either for cell lines other than red blood cells or for patients with increased blasts Patients affected primarily with severe neutropenia may benefit from the use of myeloid growth factors such as filgrastim Romiplostim and eltrombopag have shown effectiveness in raising the platelet count in myelodysplasia Azacitidine Treatment of choice for patients with high-risk myelodysplasia Can improve both symptoms and blood counts and prolong both overall survival and the time to conversion to acute leukemia Dosage: 75 mg/m2 daily for 5–7 days every 28 days; up to six cycles of therapy may be required to achieve a response Decitabine Dosage: 20 mg/m2 daily for 5 days every 28 days Can produce similar hematologic responses but has not demonstrated a benefit in overall survival compared to supportive care alone +++ Therapeutic Procedures ++ Red blood cell transfusions are indicated for severe anemia Allogeneic stem cell transplantation Only curative therapy for myelodysplasia Role is limited by advanced age of many patients and variably indolent course of disease + Outcome Download Section PDF Listen +++ +++ Complications ++ Infection Bleeding +++ Prognosis ++ Myelodysplasia is ultimately fatal, most commonly because of infection or bleeding Allogeneic transplantation is the only curative therapy, with cure rates of 30–60% depending primarily on the risk status of the disease Patients with excess blasts or CMML have a higher (30–50%) risk of developing acute leukemia, and short survival (< 2 years) without allogeneic transplantation Prognosis is favorable in Patients with MDS with isolated del(5q), with 5-year survival over 90% Patients with low-risk disease (with absence of both excess blasts and adverse cytogenetics), with similar survival International Prognostic Scoring System (IPSS) classifies patients by risk status based on Percentage of bone marrow blasts Cytogenetics Severity of cytopenias +++ When to Refer ++ All patients should be referred to a hematologist +++ When to Admit ++ Hospitalization is needed only for specific complications, such as severe infection + References Download Section PDF Listen +++ + +de Witte T et al. Allogeneic hematopoietic stem cell transplantation for MDS and CMML: recommendations from an international expert panel. Blood. 2017 Mar 30;129(13):1753–62. [PubMed: 28096091] + +Giagounidis A. Current treatment algorithm for the management of lower-risk MDS. Hematology Am Soc Hematol Educ Program. 2017 Dec 8;2017(1):453–59. [PubMed: 29222293] + +Gil-Perez A et al. Management of myelodysplastic syndromes after failure of response to hypomethylating agents. Ther Adv Hematol. 2019 May 9;10:2040620719847059. [PubMed: 31156799] + +Leitch HA et al. Iron overload in myelodysplastic syndromes: evidence-based guidelines from the Canadian consortium on MDS. Leuk Res. 2018 Nov;74:21–41. [PubMed: 30286330] + +Ogawa S. Genetics of MDS. Blood. 2019 Mar 7;133(10):1049–59. [PubMed: 30670442] + +Park S et al. Clinical effectiveness and safety of erythropoietin-stimulating agents for the treatment of low- and intermediate-risk myelodysplastic syndrome: a systematic literature review. Br J Haematol. 2019 Jan;184(2):134–60. [PubMed: 30549002] + +Steensma DP. The evolving role of genomic testing in assessing prognosis of patients with myelodysplastic syndromes. Best Pract Res Clin Haematol. 2017 Dec;30(4):295–300. [PubMed: 29156198]