Myelodysplastic Syndrome

OKEWA Japheth Siome Elizabeth Adoyo Rolex MaklagoKevin OkothKIPKIRUI Nicholas Herold Kipkirui Aduwa ClintonMARSA Subo Hassan Odoyo Mike Laura KimondoKIPRONO Dominic Rosebella Chamoro Marcia Obondi

Lecture Objectives

Introduction to MDS

Classification of MDS: FAB & WHO

Aetiology & Pathogenesis

Clinical features of MDS

Diagnosis

Management

Introduction

Group of clonal disorders of multipotent

hemopoietic stem cells

Qualitative and quantitative

abnormality in all 3 myeloid lines.

Cytopenias develop Progress to AML, but death results before

this.

Classification

FAB Classification WHO classification

Modality of classification

RA- Dysplasia in RBC only

RCMD- Dysplasia in 2 or more myeloid lineage

RAEB- Blasts increase in blood or bone marrow

5q syndrome- Good prognosis

Unclassified- Unilineage dysplasia of myeloid or megakaryocytic lineage

• Poor prognosis

Aetiology

Primary MDS• Major one• 30-50% cases are of

chromosomal abnormality• Exposure to low doses of

chemotherapy and organic chemicals

Secondary/Therapy related MDS• Long term cytotoxic chemo,

radiotherapy & Autologous transplant for lymphoma• Risk increases 4-10 years after Rx

with alkylating agents eg chlorambucil

Pathogenesis

Inherited

Acquired

DNA Damage

Myeloid Stem Cell

Myelodysplastic Clone

Myelodysplastic Syndrome

AML

Increased Angiogenesis

Immune Damage

Increased Apoptosis

Abnormal marrow microenvironment

Secondary genetic and epigenetic

abnormalities

Clinical Features

• 4/100000 incidence

• Discovered by chance• ½ of patients are over 70yrs and

< 25% are less than 50 years

• Symptoms of anemia, infection, easy bruising and bleeding• Splenomegaly uncommon unless

in CMML MDS

I just

discover

ed that

you have

MDS

I didn't know that I have MDS

Diagnosis

Observe symptoms of bone marrow

failure

Splenomegaly in 10% of

CMMLBlood film

BM aspiration & Trephine

biopsy

Chromosome analysis

Erythroid lineageBlood Bone marrow

Increased marrow cellularity

Multinucleate normoblasts

Ring sideroblastsHypocellular cells like in

aplastic anemiaFibrosisAbnormal chromatin

pattern

Hypochromic cells. Sometimes normoblasts

MacroovalocytesBasophilic

stiplingsreticulocytopenia

Myeloid (Blood)GranulocytopeniaHypogranular

neutrophilsPegler abnormality (bi-

lobed nuclei)Hypolobated neutrophil

nucleimyeloblasts

Megakaryocytic

Blood• Agranular platelets• megakaryocytes

Marrow• Macro megakaryocytes• Micronulclear• Mononuclear• Megakaryocytes with separated

nuclei• Binuclear/polynuclear forms

Cytogenetics

• Partial or total loss in chromosome 5/7 or trisomy 8• N-RAS oncogene mutation in 20 % of cases• FMS mutation in 15% of cases

ManagementBefore management, consider: Age General fitness Severity of the condition Prognosis If the disease is stable or

has progressed

Prognosis

Complications of MDS

Anemia

Increased risk of bleeding

Recurrent infections

Increased risk of cancer (AML)

Ocular manifestations: Cotton wool spots, retinal hemorrhage, corneal ulceration