MYELOPROLIFERATIVE DISORDERS

MYELODYSPLASTIC SYNDROME

Faculty of Medicine
University of Brawijaya
 Clinical Competencies

Be able to describe:
- the incidence of myelodysplastic syndrome (MDS)
- the etiology of MDS
- the pathogenesis of MDS
- the management of MDS
Be able to diagnose MDS based on clinical features
and laboratory findings

Faculty of Medicine
University of Brawijaya
 Introduction

MDS is a heterogenous group of clonal stem cell disorders

 impaired proliferation & maturation of hematopoietic
progenitor cells: anemia, leukopenia, thrombocypenia
Morphologic & functional abnormalities involving one or
more cell lines.
The clinical course is very variable: chronic, stable, midly
symptomatic disorder, progresses rapidly to acute
leukemia.
Infections and bleeding are most causes of morbidity and
mortality.

Faculty of Medicine
University of Brawijaya
 Incidence

Most commonly affects elderly patients and unusual in

person younger than 50 years.
The overall incidence : 3.5-12.6 per 100.000 per year
Aproximately 25% of patients with MDS will transform to
acute myelogenous leukemia (AML).
Most patients die as a result of the disease without
progressing to AML.
The major causes of mortality : the effects of the impaired
maturation & function of platelets, RBCs, and
neutrophils  resulting in infections & bleeding.

Faculty of Medicine
University of Brawijaya
 Etiology

Exposure to alkylating agents (cyclophosphamide,

chlorambucil, and melphalan) is associated with
increased risk of MDS.
The risk is related in dose & duration of treatment.
Generally occurs 3-7 years after exposure.
MDS occurring after chemotherapy exposure
secondary or therapy related MDS
a poor prognosis

Faculty of Medicine
University of Brawijaya
 Pathogenesis

MDS is an acquired clonal stem cell disorder

 characterized: ineffective & dysplatic hematopoiesis
 usually involves more than a single cell line
 impaired maturation & proliferation of an abnormal
clone of stem cells that replaces normal
hematopoietic progenitor
The clinical manifestations are due to impaired and abnormal
cellular maturation.
Apoptosis ↑ in MDS progenitor cells: ineffective
hematopoiesis in the BM

Faculty of Medicine
University of Brawijaya
The BM: hypercellular, ↑ hematopoiesis activity; but
peripheral cytopenias because of the impaired &
abnormal maturation within BM.
Abnormal oncogen  express progenitor cells and
deregulation of cell cycle kinetics has been implicated
in MDS: alteration in N-ras oncogen, p53 expression,
tumor suppresor genes, and transcription factors.

Faculty of Medicine
University of Brawijaya
 FAB Classification

FAB BM PB Monocyte Ring Survival

Auer rods AML
subtype blasts blasts > 1 x 109/L Sideroblast (median mo)

RA < 5% < 1% Absent No None 48 10-15%

RARS < 5% < 1% Absent No > 15% 72 5-10%

RAEB 5-20% < 5% Absent No Rare < 15% 12 30-45%

RAEB-T 21-30% > 5% Present No Rare < 15% 6 50-60%

CMML < 20% < 5% Absent Yes Rare 30 25-35%

Notes :
BM, bone marrow; AML, acute myelogenous leukemia; RA, refractory anemia;
CMML, chronic myelomonocytic leukemia; RAEB, refractory anemia with excess blast;
RAEB-T, refractory anemia with excess blast in transformation;
RARS, refractory enemia with ring sideroblast.

Faculty of Medicine
University of Brawijaya
 Ring
sideroblast
 Diagnosis

Clinical features
Anemia dominates the early course
Gradual onset of fatigue, weakness, dyspnea, pallor

Laboratory findings
Bicytopenia or pancytopenia
Isolated neutropenia
Thrombocytopenia

Faculty of Medicine
University of Brawijaya
 Dyserythropoiesis Binucleated
Normoblast

Multinuclearity

Bizzare normoblast
 Hipolobulasi Mikromegakariosit + hipolobulasi

Mikromegakariosit + hipolobulasi

Dysmegakariopoiesis

04/04/2019 12
 hipogranulasi
Giant stab

Megaloblastic changes

Dysgranulopoiesis

13
 Treatment

The therapy of MDS is generally unsatisfactory

1. Stem cell transplantation offers cure: survival rates
of 50% at 3 years
2. MDS ~ trisomy 8 may respond to cyclosporine
3. Hematopoietic growth factors can improve blood
counts  in other BM failure states : most beneficial
to patients with severe pancytopenia
- G-CSF treatment alone failed to improve survival
- Erythropoietin alone or in combination with G-CSF
can improve Hb levels, especially in low serum
erythropoietin levels

Faculty of Medicine
University of Brawijaya
Faculty of Medicine
University of Brawijaya