Department and Clinic of Haematology, - PowerPoint Presentation

Slide1

Department and Clinic of Haematology,

Blood Neoplasms, and Bone Marrow Transplantation

Chronic Myeloproliferative Neoplasms (MPN)

Ph-negative

Marta Sobas

Slide2

MPN

Ph

CML

Ph (-)

Ph (+)

PV

ET

MF

AML

Myeloid disorders

MDS

Increased

Rare

Normal (<5%)

Rare

Mature cells

Dysplasia

Blasts

AML transformation

Decreased

Yes

<5% or 5-20%

Common

Decreased

Sometimes

>=20%

-

Slide3

MPN Ph (-) epidemiology

1.

Titmarsh GJ, et al.

Am J Hematol.

2014;89:581-587.

2. Sant M, et al. Blood. 2010;116:3724-3734.

Median

age

: 60-65

y.o

.

Department and Clinic of Haematology,

Blood Neoplasms, and Bone Marrow Transplantation

Slide4

MPN definition

A

clonal

desease

Origin: pluripotential haematopoietic stem cel (HSC)

C

lassified

according to the predominant phenotypic expression of the

MPN

.

Mutation

Polycythemia vera

(PV)

Essential thrombocythemia (ET)

Chronic myeloid leukemia

Primary myelofibrosis

(PMF)

Slide5

MPN definition

DECODE

I

ndependece

of numerous cytokines

I

ncreased

and abnormal

myelopoiesis

Evolution

/

transformation

possible

.

PV

ET

PV

MF secondary

AML

PMF

ET

ET

Slide6

MPN

Ph

(-) etiologyNot known

In different subtypes of MPN Ph(-) –

mutations JAK2V617F, JAK2-exon12, CALR, MPL

appear with different frequencies There are MPN Ph(-) with no JAK, CALR, MPL mutation

(

Triple

Negative

;

TN)

PV

ET

PMF

TN

??

Slide7

What does JAK2 normally do?

It is a switch that tells blood cells to grow

MPN

Ph

(-)

etiologyMutations

JAK2, CALR, MPL:

are

not the

origin

of the MPN

Ph

(-)

These

mutations

induce constant (independent form cytocines) JAK-STAT

activation and increased myelopoiesis

JAK2

JAK2

Stat

Stat

Stat

Stat

Proliferation and survival

P

P

Cell Membrane

Cell nucleus

Erythropoietin independence

Department and Clinic of Haematology,

Blood Neoplasms, and Bone Marrow Transplantation

Slide8

Essential thrombocythemia

Department and Clinic of Haematology,

Blood Neoplasms, and Bone Marrow Transplantation

Slide9

Causes of thrombocythosis - diferentiation

Causes of Reactive Thrombocytosis

MPN with ThrombocytosisIron Deficiency

CMLInflammatory DiseasesPVMalignancyMF

Chronic InfectionsETDrugs (vinca alcalods…)

Post-splenectomy (or functionally asplenic state)Rebound thrombocythosis (following acute blood loss, post-splenectomy)MDS (5q- Sd, Sideroblastic anemia)

Department and Clinic of Haematology,

Blood Neoplasms, and Bone Marrow Transplantation

Slide10

Copyright © 2018 American Society of Hematology

Platelets

anisocytosis

Alt.

In

granulation

Platelets

agregations

Slide11

Essenthial

thrombocythemia - clinics1.

Asimptomatic – very often 2.

Increase numer of platelets in rutinary

morphology2. Thrombosis or hemorhages - sometimes

3.

Splenomegaly

–

no

or

slight

Department and Clinic of Haematology,

Blood Neoplasms, and Bone Marrow Transplantation

Slide12

Essential thrombocythemia

suspected

Blood mutation screening

JAK2V617F+ (50-60%)

CALR (20-25%)

MPL (4%)

Triple-negative (15%)

Bone marrow biopsy

to confirm diagnosis

Excluded reactive thrombocythemia ?

Department and Clinic of Haematology,

Blood Neoplasms, and Bone Marrow Transplantation

YES

+

Diagnosis

Slide13

Treatment

Low

risk of thrombosis

(<60 u.o

. with no previous history of thrombosis):

aspirin

(75 mg

daily

)

only

In

case

of

platelets

> 1000-1500/ul:

aspirin should not be used; in this

case cytoreduction should be evaluated

Patients with high

risk of

thrombosis

(> 60 y.o. or history of

previous

thrombosis

+/- cardiovascular risk factors): aspirin +

cytoreduction (Hydroxyurea or Anagrelide or

IFN)

Pregnancy:

IFN +/-

aspirin +/-

heparin

Slide14

Polycythemia vera

Department and Clinic of Haematology,

Blood Neoplasms, and Bone Marrow Transplantation

Slide15

Department and Clinic of Haematology,

Blood Neoplasms, and Bone Marrow Transplantation

Polycythemia

Slide16

Clinics of polycythemia vera

Thrombosis

,

microvascular hyperviscocity (

headache, dissiness

, skin redness, vision problems, abortions)

Tiredness

Pruritus

(

after

warm

water

bath

)Splenomegaly: present (different sizes)

Department and Clinic of Haematology,

Blood Neoplasms, and Bone Marrow Transplantation

Slide17

Increased

Hgb

and

Htc

Increased leucocytosis and thrombocytosis

is

possible

C.Rend.Soc.Biol.44:384-388 (1892)

Bone

marrow

:

Panmyelopoesis

Slide18

Department and Clinic of Haematology,

Blood Neoplasms, and Bone Marrow Transplantation

JAK2V617F+ (95%), JAK2exon 12

hypercelularity, panmyelopoyesis

Slide19

Polycythemia

vera

- treatment

Age > 60 y.o. and/or history of thrombosis

LOW riskNOHIGH riskYES

Htc < 45%

+

Aspirin

Cytoreductuve treatment (Hydroxyurea, IFN….)

+ Aspirin

Pregnancy:

IFN +/- aspirin +/- heparin

Department and Clinic of Haematology,

Blood Neoplasms, and Bone Marrow Transplantation

Slide20

Primary

and

secondary myelofibrosis

Department and Clinic of Haematology,

Blood Neoplasms, and Bone Marrow Transplantation

Slide21

Bone

marrow

fibrosis

Dacryocytes

(tear drop

poikilocytes

)

Circulating blasts

Clinics of myelofibrosis

Slide22

IPSS

,

Cervantes et al, Blood 2009;113:2895-901

DIPSS

,

Gangat N

et

al, J

Clin Oncol

2011;29:392-7

;

DIPSS plus

,

Passamonti et al,

Blood

2010;115:1703-8 Gangat N et al, J Clin Oncol 2011;29:392-7

Risk groupPointsPointsPointsLow000Intermediate-111-21-2Intermediate-223-4

3-4High>=35-6

5-6IPSSDIPSS

DIPSS

Prognostic scores in MF

Department and Clinic of Haematology,Blood Neoplasms, and Bone Marrow Transplantation

Slide23

8-11

years

2-4

years

Department and Clinic of Haematology,

Blood Neoplasms, and Bone Marrow Transplantation

Ruxolitinib

(JAK1/JAK2 inhibitor) –

inhibition

of JAK-STAT

pathway

:

Decrease

of

splenomegaly

Deacrease

of

general

symptoms

This

is not cure for MPN Ph(-)When you stop the treatment

–

all symptoms

reapere