MYELODYSPLASTIC

MYELODYSPLASTIC

MYELODYSPLASTIC

MYELODYSPLASTIC

MYELODYSPLASTIC

MYELODYSPLASTIC

MYELODYSPLASTIC

MYELODYSPLASTIC

SYNDROMES

SYNDROMES

SYNDROMES

SYNDROMES

SYNDROMES

SYNDROMES

SYNDROMES

SYNDROMES

Agnieszka Piekarska, MD

Agnieszka Piekarska, MD

Department

Department

of

of

Hematology

Hematology

and

and

Transplantology

Transplantology

Medical

Medical

University

University

of

of

Gdansk

Gdansk

DEFINITION

DEFINITION

DEFINITION

DEFINITION

DEFINITION

DEFINITION

DEFINITION

DEFINITION

a

a

heterogenous

heterogenous

group

group

of

of

acquired

acquired

bone

bone

marrow

marrow

failure

failure

disorders

disorders

characterized

characterized

by

by

peripheral

peripheral

blood

blood

cytopenias

cytopenias

as a

as a

result

result

of

of

impaired

impaired

maturation

maturation

with

with

morphologic

morphologic

evidence

evidence

of

of

dysplasia

dysplasia

in

in

the

the

bone

bone

marrow

marrow

progenitor

progenitor

cells

cells

single

single

-

-

lineage

lineage

cytopenias

cytopenias

,

,

bicytopenia

bicytopenia

or

or

pancytopenia

pancytopenia

incresed

incresed

risk

risk

for developing

for developing

AML

AML

PATHOGENESIS

PATHOGENESIS

PATHOGENESIS

PATHOGENESIS

PATHOGENESIS

PATHOGENESIS

PATHOGENESIS

PATHOGENESIS

and

and

and

and

and

and

and

and

ETIOLOGY

ETIOLOGY

ETIOLOGY

ETIOLOGY

ETIOLOGY

ETIOLOGY

ETIOLOGY

ETIOLOGY

Genetic

Genetic

mutations

mutations

and

and

their

their

accumulation

accumulation

del

del

5,

5,

del

del

7,

7,

del

del

5q

5q

Accelerated

Accelerated

apoptosis

apoptosis

Neoangiogenesis

Neoangiogenesis

(

(

disease

disease

progression

progression

)

)

Primary

Primary

MDS

MDS

:

:

familial

familial

defects

defects

(

(

impaired

impaired

hematopoiesis

hematopoiesis

or

or

DNA

DNA

repair

repair

),

),

age

age

,

,

benzene

benzene

,

,

Secondary

Secondary

MDS (

MDS (

therapy

therapy

-

-

related

related

)

)

:

:

-

-

chemotherapy

chemotherapy

:

:

alkylating

alkylating

agents

agents

e.g

e.g

.

.

chlorambucil

chlorambucil

,

,

melphalan

melphalan

,

,

Cy

Cy

,

,

autoSCT

autoSCT

-

-

ionizing

ionizing

radiation

radiation

CLASSIFICATION (WH0)

CLASSIFICATION (WH0)

CLASSIFICATION (WH0)

CLASSIFICATION (WH0)

CLASSIFICATION (WH0)

CLASSIFICATION (WH0)

CLASSIFICATION (WH0)

CLASSIFICATION (WH0)

RA

RA

=

=

refractory

refractory

anemia (

anemia (

unilineage

unilineage

erythroid

erythroid

dysplasia

dysplasia

with

with

blasts

blasts

<5%

<5%

in

in

BM)

BM)

RARS

RARS

= RA

= RA

with

with

ringed

ringed

sideroblasts

sideroblasts

(>15%)

(>15%)

RCMD

RCMD

=

=

refractory

refractory

cytopenia

cytopenia

with

with

multilineage

multilineage

dysplasia

dysplasia

(blasts<5%

(blasts<5%

in

in

BM)

BM)

RCMD

RCMD

-

-

RS

RS

= RCMD

= RCMD

with

with

ringed

ringed

sideroblasts

sideroblasts

RAEB

RAEB

=RA

=RA

with

with

excess

excess

blasts(<20%)

blasts(<20%)

-

-

RAEB

RAEB

I,II

I,II

5q

5q

-

-

syndrome

syndrome

= MDS <5%

= MDS <5%

blasts

blasts

with

with

del

del

(5q)

(5q)

MDS

MDS

unclassifiable

unclassifiable

MDS/MPS

MDS/MPS

–

–

CMML =

CMML =

chronic

chronic

myelomonocytic

myelomonocytic

leukemia

leukemia

CLINICAL FEATURES

CLINICAL FEATURES

CLINICAL FEATURES

CLINICAL FEATURES

CLINICAL FEATURES

CLINICAL FEATURES

CLINICAL FEATURES

CLINICAL FEATURES

Asymptomatic

Asymptomatic

Symptoms

Symptoms

suggestive

suggestive

of

of

a

a

blood

blood

disorder

disorder

(

(

fatigue

fatigue

,

,

exercise

exercise

intolerance

intolerance

,

,

infections

infections

,

,

inappropriate

inappropriate

bleeding

bleeding

or

or

bruising

bruising

)

)

Anemia (Hb<10%,MCV N/>) 80%

Anemia (Hb<10%,MCV N/>) 80%

Neutropenia

Neutropenia

40%

40%

Thrombocytopenia

Thrombocytopenia

30

30

-

-

45%

45%

CLINICAL FEATURES

CLINICAL FEATURES

CLINICAL FEATURES

CLINICAL FEATURES

CLINICAL FEATURES

CLINICAL FEATURES

CLINICAL FEATURES

CLINICAL FEATURES

BM:

BM:

dyserytropoiesis

dyserytropoiesis

(

(

megaloblastic

megaloblastic

maturation

maturation

,

,

abnormalities

abnormalities

of

of

erythroblast

erythroblast

nuclei

nuclei

,

,

iron

iron

-

-

laden

laden

mitochondria=sideroblasts

mitochondria=sideroblasts

)

)

dysgranulopoiesis

dysgranulopoiesis

(

(

hypogranulation

hypogranulation

,

,

hypo

hypo

-

-

or

or

hypersegmentation

hypersegmentation

,

,

excess

excess

blasts

blasts

)

)

dysmegakariopoiesis

dysmegakariopoiesis

(

(

giant

giant

or

or

small

small

,

,

hypogranular

hypogranular

)

)

Trephine

Trephine

core

core

BM

BM

biopsy

biopsy

:

:

mostly

mostly

normo

normo

-

-

or

or

hypercellular

hypercellular

,

,

sometimes

sometimes

hypocellular

hypocellular

ALIP (

ALIP (

abnormal

abnormal

localization

localization

of

of

immature

immature

precursors

precursors

)

)

NATURAL

NATURAL

NATURAL

NATURAL

NATURAL

NATURAL

NATURAL

NATURAL

HISTORY/PROGNOSIS

HISTORY/PROGNOSIS

HISTORY/PROGNOSIS

HISTORY/PROGNOSIS

HISTORY/PROGNOSIS

HISTORY/PROGNOSIS

HISTORY/PROGNOSIS

HISTORY/PROGNOSIS

International

International

Prognostic

Prognostic

Scoring

Scoring

System for

System for

Patients

Patients

with

with

MDS

MDS

Risk

Risk

groups

groups

:

:

low=0,

low=0,

intermediate

intermediate

I 0.5

I 0.5

-

-

1,

1,

intermediate

intermediate

II 1.5

II 1.5

-

-

2, high

2, high

≥

≥

2.5

2.5

2.0

2.0

21

21

-

-

30

30

1.5

1.5

11

11

-

-

20

20

1.0

1.0

Poor

Poor

0.5

0.5

Intermediate

Intermediate

5

5

-

-

10

10

2

2

-

-

3

3

0.0

0.0

Good

Good

<5

<5

0

0

-

-

1

1

Score

Score

Cytogenetics

Cytogenetics

Marrow

Marrow

Blasts

Blasts

(%)

(%)

Cytopenia

Cytopenia

TREATMENT

TREATMENT

TREATMENT

TREATMENT

TREATMENT

TREATMENT

TREATMENT

TREATMENT

transfusion

transfusion

support

support

(

(

blood

blood

,

,

platelets

platelets

)

)

iron

iron

chelatation

chelatation

(

(

Desferrioxamine

Desferrioxamine

)

)

tranexamic

tranexamic

acid

acid

growth

growth

factors

factors

(

(

G

G

-

-

CSF

CSF

, EPO)

, EPO)

immunosuppresive

immunosuppresive

treatment

treatment

(

(

ATG+CsA+Pred

ATG+CsA+Pred

)

)

induction

induction

AML

AML

-

-

like

like

chemotherapy

chemotherapy

or

or

low

low

-

-

dose

dose

CHT

CHT

allogeneic

allogeneic

stem

stem

cell

cell

transplantation

transplantation

(

(

alloSCT

alloSCT

)

)

Alternatives

Alternatives

/

/

clinical

clinical

trials

trials

:

:

steroids

steroids

,

,

thalidomide

thalidomide

,

,

lenalidomide

lenalidomide

,

,

azacitidine

azacitidine

,

,

decitabine

decitabine

,

,

clofabine

clofabine

,

,

amifostine

amifostine

,

,

arsenic

arsenic

trioxide

trioxide

,

,

inhibitors

inhibitors

of

of

angiogenesis

angiogenesis