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Myelodysplastic Syndromes Overview ? * A group of clonal stem cell disorders characterized by maturation defects ---Associated with ineffective hematopoiesis ---High risk of transformation to AML --- can see anemias, infections, and bleeding---- blast count below 20%
MDS Testing ? * CBC – pancytopenia ----Peripheral blood – dysplasia in one or all cell lines ----Bone marrow aspiration & biopsy <20% blasts---- Flow cytometry – confirms absence of AML ----Cytogenetics ...... * nothing in blood can make Dx , need BM biopsy
MDS BM Morphology ? * Erythroid dysplasia - see Ringed sideroblasts..... * Neutrophil dysplasia - Decreased secondary granules (hypogranular)and Pseudo Pelger-Huet cells .... * Megakaryocyte dysplasia - Myeloblasts MUST be less than 20% and NO Auer rods
MDS PB Morphology ? * Pseudo-Pelger-Huet cells ---Hypogranular neutrophils ---Giant platelets ---Macrocytes ---Poikilocytes (schistocytes and spherocytes are NOT seen) ---Relative or absolute monocytosis ---Myeloblasts MUST be <10% of the leukocytes
MDS WHO Classification ? * Refractory cytopenia with unilineage dysplasia (RCUD)-- Refractory anemia, refractory neutropenia, refractory thrombocytopenia <5% of cases .....*Refractory anemia with Ringed Sideroblasts (RARS) --- <5% of cases
continued.... * Refractory cytopenia with multilineage dysplasia (RCMD) -- 70% of cases – in more than 1 cell line .....* Refractory anemia with excess blasts (RAEB) -- 25% of cases – morethan 3, less than 20
continued... * MDS with isolated del(5q) --5% of cases ....*MDS, unclassified -- <5% of cases
Refractory Cytopenia with Unilineage Dysplasia (RCUD) ? * <5% blasts in the BM.... * Dysplasia in >10% of cells in one lineage
Refractory Anemia with Ringed Sideroblasts (RARS) ? * >15% ringed sideroblasts in the bone marrow ---- 10 or more iron-laden mitochondria occupying more than 1/3 of nuclear rim
Refractory Cytopenia with Multilineage Dysplasia (RCMD) ? * Severe dysplasia in two or more cell lines.... * RCMD-RS --> increased ringed sideroblasts in addition to above
Refractory Anemia with Excess Blasts (RAEB) ? * 5-9% = RAEB-I ...... * 10-19% = RAEB-II  shorter survival and increased risk of developing AML ...... * Dysplasia present ..... *NO Auer rods
MDS with Isolated del(5q) ? * 5q- Syndrome, and best prognosis .... * Severe anemia, normal platelet count ..... * RBC transfusions may be necessary .....*BM with micromegakaryocytes (mono or bilobed nuclei), <5% myeloblasts
Myeloproliferative Disorders Overview ? * Group of disorders with increased proliferative drive in BM.... * BM fibrosis and PB cytopenias.... * BM doesn't make enough RBCs bc of fibrosus.... * also see high numbers of one type of cells
MPD Testing ? * CBC – increase in one or more cell lines .... * Peripheral blood – maturation without excess blasts, should not be there ..... * Bone marrow aspiration & biopsy - <20% blasts -- Maturation of involved cell lines
continued.... * Erythropoietin levels - markedly decreased in PV.... * Uric acid – increased due to cell turn-over
Chronic Myeloid Leukemia (CML) ? * synthesis of active BCR-ABL tyrosine kinase --> t(9;22)the Philadelphia Chromosome .... * Sea-blue histiocytes .... * all levels of granulocytic maturation (<5% blasts); nucleated RBCs; increased Bo & Eo; few promyelocytes; giant platelets
Chronic Myeloid Leukemia (CML) clinically ? * splenomegaly - giant spleens ... * indigestion and fatigue ... * high WBC count with low blast count .... * can get ALL or AML
Polycythemia Rubra Vera (PV) ? * mutations in tyrosine kinase JAK2 --> decreased need for erythropoietin in RBC production .... * Increased total blood volume  viscosity with abnormal platelet function --> bleeding and thrombosis .... * Hemoglobin = 14-28 gm/dl *Hematocrit = >60%
Essential Thrombocythemia (ET) ? * activating point mutations in JAK2 or MPL --> decreased need for thrombopoietin.... * megakaryocytes markedly increased ... * Giant platelets .... * Erythromelalgia – throbbing & burning of hands and feet .... * super high platelets and Bleed
Primary Myelofibrosis ? * activating JAK2 or MPL mutations.... * see BM fibrosus, so causes a dry tap on biopsy .... * see Osteosclerosis... * erythroblastosis; tear drop RBCs; giant platelets; increased basophils .... * die in 3 - 4 years
Created by: thamrick800