Myelodysplastic Syndrome

Myelodysplastic Syndrome Group of clonal disorders of hematopoietic stem cells characterized by cellular dysplasia and ineffective hematopoiesis Results in cytopenias and dysmyelopoiesis Variable risk of transformation to acute leukemia

Pathophysiology Primary MDS or Secondary MDS A clonal mutation in hematopoietic stem cells Bone marrow failure due to ineffective hematopoiesis Increased cytokines (TNF-a) inhibit hematopoiesis Increased apoptosis Results in futile cycling of blood cells with impaired production of mature blood cells

Prevalence Mainly a disorder of older patients, rarely presents before age 50 Median age is 65 years Male predominance

Clinical Presentation Non specific signs and symptoms of various cytopenias Fatigue, SOB, exercise intolerance, pallor, tachycardia Mucosal bleeding, petechiae, ecchymoses Infection, fever B-symptoms are uncommon Splenomegaly and lymphadenopathy are rare

Diagnosis Anemia uniformly present with decreased reticulocytosis >50% present with pancytopenia 50% present with associated neutropenia <5% isolated neutropenia or thrombocytopenia Cytopenia with normal or hypercellular bone marrow with single or multi-lineage dysplasia

Morphology Peripheral changes include oval macrocytic red cells, hypogranular granulocytes with the pseudo-Pelger–Huët anomaly, and giant platelets.

Morphology Megaloblastic red-cell precursors with multiple nuclei or asynchronous maturation of the nucleus and the cytoplasm

Morphology Ringed sideroblasts, erythroid precursors with iron-laden mitochondria

Classification Refractory Anemia (RA) Disease Peripheral Blood Bone Marrow Refractory Anemia (RA) Anemia No or rare blasts Erythroid dysplasia only < 5% blasts < 15% ringed sideroblasts Refractory Anemia with Ringed Sideroblasts (RARS) No blasts >15% ringed sideroblasts < 5% blasts Refractory cytopenia with multilineage dysplasia (RCMD) Cytopenia No Auer rods < 1 × 109/L monocytes Dysplasia in 10% of cells in 2 or more myeloid cell lines < 5% blasts in marrow < 15% ringed sideroblasts

Classification Cont. Disease Peripheral Blood Bone Marrow Refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS) Cytopenia No or rare blasts No Auer rods < 1 × 109/L monocytes Dysplasia in 10% of cells in 2 or more myeloid cell lines < 5% blasts in marrow > 15% ringed sideroblasts Refractory anemia with excess blasts-1 (RAEB-1) Cytopenias < 5% blasts Unilineage or multilineage dysplasia 5% to 9% blasts Refractory anemia with excess blasts-2 (RAEB-2) 5% to 19% blasts Auer rods ±  < 1 × 109/L monocytes 10% to 19% blasts ±Auer rods 

Classification cont. Disease Peripheral Blood Bone Marrow Myelodysplastic syndrome, unclassified (MDS-U) Cytopenias No or rare blasts No Auer rods Unilineage dysplasia in granulocytes or megakaryocytes < 5% blasts MDS associated with isolated del(5q) Anemia Platelets normal or increased Normal to increased megakaryocytes with hypolobated nuclei Isolated del(5q)