Myelodysplastic SyndromeMyelodysplastic Syndrome

Myelodysplastic SyndromeMyelodysplastic Syndrome

Group of clonal disorders of Group of clonal disorders of hematopoietic stem cells hematopoietic stem cells characterized by cellular dysplasia characterized by cellular dysplasia and ineffective hematopoiesis and ineffective hematopoiesis

Results in cytopenias and Results in cytopenias and dysmyelopoiesis dysmyelopoiesis

Variable risk of transformation to Variable risk of transformation to acute leukemia acute leukemia

PathophysiologyPathophysiology

Primary MDS or Secondary MDSPrimary MDS or Secondary MDS A clonal mutation in hematopoietic stem A clonal mutation in hematopoietic stem

cellscells Bone marrow failure due to ineffective Bone marrow failure due to ineffective

hematopoiesis hematopoiesis Increased cytokines (TNF-a) inhibit Increased cytokines (TNF-a) inhibit

hematopoiesishematopoiesis Increased apoptosisIncreased apoptosis Results in futile cycling of blood cells with Results in futile cycling of blood cells with

impaired production of mature blood cells impaired production of mature blood cells

Prevalence Prevalence

Mainly a disorder of older patients, Mainly a disorder of older patients, rarely presents before age 50 rarely presents before age 50

Median age is 65 yearsMedian age is 65 years Male predominance Male predominance

Clinical Presentation Clinical Presentation

Non specific signs and symptoms of various Non specific signs and symptoms of various cytopeniascytopenias

• Fatigue, SOB, exercise intolerance, pallor, Fatigue, SOB, exercise intolerance, pallor, tachycardia tachycardia

• Mucosal bleeding, petechiae, ecchymosesMucosal bleeding, petechiae, ecchymoses• Infection, feverInfection, fever

B-symptoms are uncommon B-symptoms are uncommon Splenomegaly and lymphadenopathy are rareSplenomegaly and lymphadenopathy are rare

Diagnosis Diagnosis

Anemia uniformly present with decreased Anemia uniformly present with decreased reticulocytosisreticulocytosis

>50% present with pancytopenia>50% present with pancytopenia 50% present with associated neutropenia50% present with associated neutropenia <5% isolated neutropenia or <5% isolated neutropenia or

thrombocytopenia thrombocytopenia Cytopenia with normal or hypercellular Cytopenia with normal or hypercellular

bone marrow with single or multi-lineage bone marrow with single or multi-lineage dysplasiadysplasia

Morphology Morphology

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

MorphologyMorphology

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

Morphology Morphology

Ringed Ringed sideroblasts, sideroblasts, erythroid erythroid precursors with precursors with iron-laden iron-laden mitochondriamitochondria

ClassificationClassification

DiseaseDisease Peripheral BloodPeripheral Blood Bone MarrowBone Marrow

Refractory Anemia (RA) Anemia

No or rare blasts

Erythroid dysplasia only

< 5% blasts

< 15% ringed sideroblasts

Refractory Anemia with Ringed Sideroblasts (RARS)

Anemia

No blasts

Erythroid dysplasia only >15% ringed sideroblasts < 5% blasts

Refractory cytopenia with multilineage dysplasia (RCMD)

CytopeniaNo or rare blastsNo 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.Classification Cont.Disease Peripheral Blood Bone Marrow

Refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS)

CytopeniaNo or rare blastsNo 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% blastsNo Auer rods< 1 × 109/L monocytes

Unilineage or multilineage dysplasia 5% to 9% blasts No Auer rods

Refractory anemia with excess blasts-2 (RAEB-2)

Cytopenias 5% to 19% blasts Auer rods ± < 1 × 109/L monocytes

Unilineage or multilineage dysplasia 10% to 19% blasts ±Auer rods 

Classification cont. Classification cont.

DiseaseDisease Peripheral BloodPeripheral Blood Bone MarrowBone Marrow

Myelodysplastic syndrome, unclassified (MDS-U)

CytopeniasNo or rare blastsNo Auer rods

Unilineage dysplasia in granulocytes or megakaryocytes < 5% blasts No Auer rods

MDS associated with isolated del(5q)

Anemia < 5% blastsPlatelets normal or increased

Normal to increased megakaryocytes with hypolobated nuclei < 5% blastsNo Auer rodsIsolated del(5q)