This document discusses Myelodysplastic Syndromes (MDS), a group of clonal disorders affecting hematopoietic stem cells. MDS results in cytopenias due to dysplasia in the myeloid cell lines. It can progress to acute myeloid leukemia (AML) or cause death from bone marrow failure before transforming. The document covers classification systems for MDS (FAB and WHO), aetiology involving genetic abnormalities, clinical features such as anemia and infections, diagnosis using blood tests and bone marrow biopsy, and management considerations depending on patient factors and disease severity/progression.

1. OKEWA Japheth Siome Elizabeth Adoyo Rolex Maklago Kevin Okoth
KIPKIRUI Nicholas Herold Kipkirui Aduwa Clinton
MARSA Subo Hassan Odoyo Mike Laura Kimondo
KIPRONO Dominic Rosebella Chamoro Marcia Obondi

2. Lecture Objectives
Introduction to MDS
Classification of MDS: FAB & WHO
Aetiology & Pathogenesis
Clinical features of MDS
Diagnosis
Management

3. 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.

4. FAB Classification WHO classification

5. 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

6. 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

7. 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

8. 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

9. I didn't know
that I have
MDS

11. Diagnosis
Observe
symptoms of
bone marrow
failure
Splenomegaly
in 10% of
CMML
Blood film
BM aspiration
& Trephine
biopsy
Chromosome
analysis

12. Erythroid lineage
Blood Bone marrow
Increased marrow
cellularity
Multinucleate
normoblasts
Ring sideroblasts
Hypocellular cells like in
aplastic anemia
Fibrosis
Abnormal chromatin
pattern
Hypochromic
cells. Sometimes
normoblasts
Macroovalocytes
Basophilic
stiplings
reticulocytopenia

14. Myeloid (Blood)
Granulocytopenia
Hypogranular
neutrophils
Pegler abnormality (bi-
lobed nuclei)
Hypolobated neutrophil
nuclei
myeloblasts

15. Megakaryocytic
Blood
• Agranular platelets
• megakaryocytes
Marrow
• Macro megakaryocytes
• Micronulclear
• Mononuclear
• Megakaryocytes with separated
nuclei
• Binuclear/polynuclear forms

16. 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

17. Management
Before management,
consider:
 Age
 General fitness
 Severity of the
condition
 Prognosis
 If the disease is stable
or has progressed

18. Prognosis

19. Complications of MDS
Anemia
Increased risk of bleeding
Recurrent infections
Increased risk of cancer (AML)
Ocular manifestations: Cotton wool spots,
retinal hemorrhage, corneal ulceration