Myelodysplastic Syndrome (MDS)

Dr. Fatma Al-Qhtani

MDS Disorders of multipotent hemopoietic

stem cell Heterogenous group Hemopoiesis is ineffective and

morphological dysplastic ( Blood/ BM) Tendency to evolve into acute

leukemia Elderly patient

FAB (1982) Refractory anemia (RA) Refractory anemia with ring sideroblast

(RARS) Refractory anemia with excess blast (RAEB) Refractory anemia with excess blast in

transformation (RAEBt) Chronic myelomonocytic leukemia (CMML)

Refractory Anemia Peripheral blood:

1. Anemia

2. Blast< 1%3. Monocytes < 1 X 109

Bone Marrow:

1. Blast < 5%

2. Ringed sideroblasts < 15% of erythroblast

RARS Peripheral blood:

1. Anemia

2. Blast < I%3. Monocytes < 1x 109

Bone marrow:

1. Blast < 5%

2. Ringed sideroblasts > 15% of erythroblast

RAEB Peripheral blood:

1. Anemia2. Monocytes <1 x 10 9

3. Blasts > 1% , but < 5% Bone marrow:

1. Blasts > 5% and/ or < 20%

CMML Peripheral blood:1. Monocytes > 1 x109

2. Blast < 5 % Bone marrow:

1. Blast up to 20%

2. Increased of promonocytes

WHO Refractory anemia Refractory anemia e ringed siderblast Refractory cytopenia e multilineage dysplasia Refractory cytopenia e multilineage dysplasia

& ringed sideroblasts Refractory anemia e excess blast-1 Refractory anemia e excess blast-2 Myelodysplastic syndrome unclassified MDS associated e isolated del (5q)

WHOSubtype Blood Bone Marrow

RA Anemia Erythroid dysplasia only

RARS Anemia Erythroid dys

>15% ringed

RCMD Bi- pancytopenia >10%Dysp in 2 or more cell lineage

RCMD-RS Bi-pancytopenia >10%Dys 2 or more cell lineage

>15% ringed

WHOsubtype Blood Bone Marrow

RAEB-1 Cytopenia

<5% blast

Uni-multilineage dys, 5-9%blast

RAEB-2 Cytopenia,

5-19%blast or Auer rods

Uni-multi dys

10-19%blast

Or Auer rods

MDS-U cytopenia Myeloid or megakaryocte dys

MDS with 5q Anemia,nor or increased PLT

Mega e hypolobated nuclei, <5%blast

Relation FAB & WHOFAB WHO

RA RA(unilineage)

RCMD

5q-syndrome

RARS RARS(unilineage)

RCMD-RS

RAEB RAEB-1

RAEB-2

RAEBt AML e multilieage dys

AML & MDS-TR

CMML Myelodysplastic/ myeloproliferative disease

Etiology Primary unknown1. Case control study shown increased

incidence in: smoker, agricultural workers, plant and machine operator, ionizing radiation, organic chemical

Secondary or therapy related MDS1. Cytotoxic chemotherapy

2. Median time is 4-5 years

Clinical feature

1. Incidental blood count

2. Bone marrow failure symptoms & signs

3. Fatigue due to anemia

4. Bleeding

5. infections

CMML Splenomegaly (10%) Maculopapular skin infiltration Monocytic pleural or pericardial

effusion JMML (MPD/MDS)1. Pallor, bleeding,

hepatosplenomegaly, skin involvement

Laboratory Feature Anemia 30- 50 % are pancytopenic 20% anemia in combination e

neutropenia or thrombocytopenia < 5% isolated neutropenia or

thrombocytopenia

Erythroid Oval macrocytosis Anisopoikiloctosis Hypochromic red cell fragments Basophilic stippling NRBCs

Granulocytic Nuclear hypolobulation (Pelger) Nuclear Hypersegmentation Ring nuclei coarse chromatin clumping Cytoplasmic hypogranulation or

agranulition

Monocytic Abnormal nuclear lobulation

Megakaryocte Agranular platelets Giant platelets

Erythroid (BM) Ringed sideroblast Vacuolated cytoplasm Multinuclearity ( bi or tri) Internuclear bridging Erythroid hypoplasia

Myeloid (BM) Loss of primary & secondary granules increased Blasts Increased eosinophils & or Basophils

Megakaryocytes (BM) Micromegakaryocytes Large mono or binuclear

megakaryocytes Large megakaryocytes with widely

dispersed nuclei

Prognosis Poor:( FBC & BF)

1. Anemia

2. Neutropenia

3. Thrombocytopenia

4. Presence of blast

5. Raised lactic dehydrogenase

Prognosis Poor ( Marrow Aspirate):

1. Blast > 10%

2. Trilineage dysplasia Trephine

1. Abnormal localization of immature precursors ( Erythroid/ megakaryocytes)

Prognosis Chromosome analysis:

1. Monosomy 7

2. Complex Karyotype

3. Karyotypic evolution Molecular Studies:

1. N- RAS mutation

2. P53 mutation

Management

1. Observation

2. Supportive care

3. Intensive chemotherapy

4. Allogenic or autologous transplant

5. Cytotoxic therapy

6. Immunosupperessive agents

THANK YOU