Blood Neoplasms and Bone Marrow Transplantation Chronic Myeloproliferative Neoplasms MPN Phnegative Marta Sobas MPN Ph CML Ph Ph PV ET MF AML Myeloid disorders MDS Increased ID: 779646
Download The PPT/PDF document "Department and Clinic of Haematology," is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
Slide1
Department and Clinic of Haematology,
Blood Neoplasms, and Bone Marrow Transplantation
Chronic Myeloproliferative Neoplasms (MPN)
Ph-negative
Marta Sobas
Slide2MPN
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%
-
Slide3MPN 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
Slide4MPN 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)
Slide5MPN definition
DECODE
I
ndependece
of numerous cytokines
I
ncreased
and abnormal
myelopoiesis
Evolution
/
transformation
possible
.
PV
ET
PV
MF secondary
AML
PMF
ET
ET
Slide6MPN
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
??
Slide7What 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
Slide8Essential thrombocythemia
Department and Clinic of Haematology,
Blood Neoplasms, and Bone Marrow Transplantation
Slide9Causes 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
Slide10Copyright © 2018 American Society of Hematology
Platelets
anisocytosis
Alt.
In
granulation
Platelets
agregations
Slide11Essenthial
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
Slide12Essential 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
Slide13Treatment
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
Slide14Polycythemia vera
Department and Clinic of Haematology,
Blood Neoplasms, and Bone Marrow Transplantation
Slide15Department and Clinic of Haematology,
Blood Neoplasms, and Bone Marrow Transplantation
Polycythemia
Slide16Clinics 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
Slide17Increased
Hgb
and
Htc
Increased leucocytosis and thrombocytosis
is
possible
C.Rend.Soc.Biol.44:384-388 (1892)
Bone
marrow
:
Panmyelopoesis
Slide18Department and Clinic of Haematology,
Blood Neoplasms, and Bone Marrow Transplantation
JAK2V617F+ (95%), JAK2exon 12
hypercelularity, panmyelopoyesis
Slide19Polycythemia
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
Slide20Primary
and
secondary myelofibrosis
Department and Clinic of Haematology,
Blood Neoplasms, and Bone Marrow Transplantation
Slide21Bone
marrow
fibrosis
Dacryocytes
(tear drop
poikilocytes
)
Circulating blasts
Clinics of myelofibrosis
Slide22IPSS
,
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
Slide238-11
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