Hematology 3

Front 1

AML – basic characteristics

Back 1

Complex CLONAL disease with considerable phenotypical and genotypical heterogeneity

Proliferation and accumulation of immature haematopoietic cells in the bone marrow and blood

Evalutaion and prognosis hase changed over 20 years, however, still most patients will die of the disease or of the therapy.

Front 2

AML - epidemiology

Back 2

1,2% of all cancer deaths
Median age at diagnosis: 60-65 years
AML: 60-90% of adult leukemias in adults

Front 3

AML - etiology

Back 3

No firm etiology factor known at this point. except the regular: smoking inhertance etc.

Front 4

Pathogenesis of AML (7)

Back 4

Inappropriate proliferation
Differentiation blockade
Escape from programmed cell death
Self renewal
Loss of cell cycle control
Genomic instability
Leukemia cell dissemination

Front 5

What is a leukemic stem cell?

Back 5

only few leukemic blasts have capacity of self renewal. 1 in 10^5 leukemia cells.

Front 6

phenotype of leukemia stem cell

Back 6

CD34+CD38-

Front 7

What differentiation factor is the most comman in AML?

Back 7

Transcription factors:
In AML commonly disrupted by chromosomal translocation
or point mutations.

---> STOP in differantiation,
Increased self renewal capacity

Front 8

Inappropriate proliferation
Which molecules are the most important?
Which is expressed in almoast all AML?
Other?

Back 8

Receptor tyrosine kinase and Intracellular thyrosine kinase are crucial.
FLT3 tyrosine kinase: expressed almost in all AML

Other tyrosine kinases involved: c-KIT, JAK-2 etc.

Front 9

How does AML escape apoptosis?

Back 9

TK activation-->PI-3 kinase---> Increased BCL-2 (antiapoptotic)

Front 10

How is AML classified?

Back 10

According to FAB (M0-M7) or WHO classification.

Front 11

What is an Auer rod?

Back 11

Auer rods can be seen in the leukemic blasts of acute myeloid leukemia. Auer rods are clumps of azurophilic granular material that form elongated needles seen in the cytoplasm of leukemic blasts.

Front 12

What is an Auer rod?

Back 12

Auer rods can be seen in the leukemic blasts of acute myeloid leukemia. Auer rods are clumps of azurophilic granular material that form elongated needles seen in the cytoplasm of leukemic blasts.

Front 13

Diagnosis of AML, special consideration
Spleen, LN, Skin, mtb and electrolyes.

Back 13

Splenomegaly: rare
Lymphadenopathy: rare
CNS involvement: 5-7%

Skin involvement: 10%
Metabolic and electrolyte derrangement

Front 14

Peripheral blood finding to make diaagnosis of AML?

Back 14

leucocytosis with blasts + anemia, thrombocytopenia in 90%
10%: pancytopenia (or normal leukocyte count with blasts)

Front 15

AML – risk assesment is based on what?

Back 15

Chromosomal abberations and age.

Front 16

General strategy and stratification of treatment of AML when: >65 yo

Back 16

Palliative approach

Front 17

General strategy and stratification of treatment of AML when: <65 yo

Back 17

Intensive chemo with curative intent +- BMT

Front 18

General strategy and stratification of treatment of AML when: Acute promyelocytic leukemia (APL)

Back 18

ATRA + chemotherapy

Front 19

Overal survival (OS) in AML?

Back 19

40% in 5 years

Front 20

Epidemiology, etiology of ALL

Back 20

Incidence: 1,1 – 1,4/100 000
Double peak incidence: 4 years and 50-80
Etiology: not known
Risks:
Inherited chromosomal aberrations: +21,

Front 21

T- ALL involves more frequently?
B-ALL involves more frequently?

Back 21

T- ALL involves more frequently mediastinal lymph nodes
B- ALL: spleen, liver

Front 22

Patophysiology of ALL

Back 22

ALL is derived from morphologically immature precursors of lymphocytes
Primarily involves bone marrow
Infiltrates: lymph nodes, spleen, liver, testicules, other parenchymatous orgáns, CNS.
T- ALL involves more frequently mediastinal lymph nodes
B- ALL: spleen, liver

Front 23

Cytogenetics ALL

Back 23

t(9,22) = Ph chromosome, other: t(4;11), t(8;21), t(2;8), t(8;14)

Front 24

ALL: classification. acc to FAB

Back 24

L1-L3
Does not have influence of the mangement of ALL

Front 25

ALL – making diagnosis: Blood
Bone marrow smear

Back 25

Blood counts: leukocytosis + blasts >20%, leukopenia, anemia, thrombocytopenia
Bone marrow smear: blasts >20%, PAS positivity

Front 26

What is Imatinib mesylate (Glivec®)?

Back 26

first specific TKI (TyrosineKnase Inhibitor) of bcr/abl
mechanism: occupation of the binding site for ATP
first significant breakpoint in the CML management:

Front 27

Myeloprolipherative diseases (MPD):
Common signes?

Back 27

Common signes: proliferation 1-3 cell lines with excess in peripheral blood, extramedullary haemopoiesis, bone marrow fibrosis

Front 28

Myeloprolipherative diseases (4)

Back 28

Chronic myeloid leukemia (CML)
Polycythaemia Vera (PV)
Essential thrombocytopenia (ET)
Primary myelofibrosis (MF)

Front 29

Which translocation os super important when it comes to MPD?

Back 29

Philadelphia!!!
(BCR-abl

Front 30

Chronic myeloid leukemia (CML) definition:
Epidemiology, risk factor, pathophys?

Back 30

Definition: myeloprolipherative clonal disease derived from a stem cell, bcr/abl rearrangement involved
Epidemiology: incidence 1/100 000
Etiology: unknown
Risk factors: radiation
Pathophysiology: gene rearrangment bcr, abl bcr/abl – tyrosinkinase. Cytogenetic marker: t(9;22) = Ph chromosome.

Front 31

CML pathophys:

Back 31

Pathophysiology: gene rearrangment bcr, abl bcr/abl – tyrosinkinase. Cytogenetic marker: t(9;22) = Ph chromosome.

Front 32

What is the ccourse of CML? What happens during the phases?

Back 32

Chronic phase: 50% patients diagnosed incidentialy: sweating, weight loss, pruritus, left hypochondrium pressure

Acceleration phase: symptoms stressed, treatment with decreased effect (need for increase effect)

Blastic phase: anaemic syndrome, infection, haemorhagia, left hypochondrial tension – splenomegaly

Front 33

Diagnosis of CML, blood in different phases?
+ bonemarrow histo

Back 33

Blood counts:
Chronic phase: leukocytosis with left shift to myeloblasts
Acceleration phase: Number of blasts in peripheral blood or bone marrow: 10-30%, eosinophils and basophils: > 20%
Blastic phase: blasts >30%, blasts and promyelocytes > 50%

Bone marrow - histology: different degree of fibrosis

Front 34

What is the risk assement of CML called?

Back 34

Hasford's index.

Front 35

Treatment of CML?
How does it work?

Back 35

Imatinib mesylate (Glivec®)

first specific inhibitor of tyrosinkinase bcr/abl (TKI)
mode of action: occupies binding site ATP
standard dose: 400mg/D p.o.
90,3% of patients survive after 54 months of therapy
Tolerance: very good
Side effects: swellings, rush, neutropenia

Front 36

When can there be resistant to Imatinib (in CML treatment)
What do you do then?

Back 36

When mutation of BCR-ABL.
Give Nilotinib (Obtained by crystalic projecting of imatinib
)

Front 37

What is Dasatinib?

Back 37

multi target“ kinase inhibitor (Bcr-Abl, SRC, TEC, PDGFR, kit etc)
In CML treatment
But is not active against some mutations.

Front 38

Polycythaemia vera (PV)
incidence
Median age
etiology
Definition
Pathophys

Back 38

Incidence: 0,5 – 0,8/100 000
Median: 60 years
Etiology: unknown in most cases (some: ionizing radiation)
Definition: myeloprolipherative clonal disease derived from a stem cell with major erythrocyte prolipheration
Patophysiology: > 25% erythrocyte mass, erythrocytosis, hyperviscosity, hyperuricaemia, trend to vessel complications

Front 39

What must be done for PV diagnosis?

Back 39

1. exclude secondary or relative erythrocytosis
2. Exclude othe MPDs (if Jak-2 is + then it is not PV)

Front 40

PV treatment

Back 40

Blood draw
if not work:Litalir (in older pat)
All pat will get anti aggregation (aspirin)

Front 41

Essential thrombocythaemia (ET)
Incidence
Definition
Blood
Symptoms acc to blood count?

Back 41

Incidence: 0,1/100000
In majority clonal disease with accelerated proliferation of megakaryocyte line
Peripheral blood count: PLT > 600 x109/l, slight leukocytosis with a left shift.
Blood counts: 1. Bleeding (PLT > 1500 x109/l), 2. Thrombosis (PLT < 1500 x109/l). Thrombosis in atypical sites: v. jugularis, v. portae etc.

Front 42

Treatment of ET

Back 42

Hydroxyurea (Litalir, as in PV) in men, women after fertile age
Interferon -  (3MU 3 x in a week) in women in fertile age
Anagrelide

Front 43

Definition of myeloma?

Back 43

Definition: abnormal proliferation and accummulation of plasma cells producing one type of paraproteins . Clinical course has typical picture

Front 44

Multiple myeloma: epidemiology

Back 44

Approximately 1% of all cancers
second most prevalent haematological cancer (After lymphomas)
Median age at diagnosis: 71 years

Front 45

Pathogenesis of MM

Back 45

MM arises from a B cell of the normal germinal centre. Initially, MM is confined to the bone marrow, but tumours can acquire the ability to grow outside the bone marrow

Front 46

Bone marrow pathophysiology in MM

Compare Osteoblast and osteoclast activity.

Back 46

In normal bone, osteoblast and osteoclast function is balanced by the actions of RANKL and OPG
In MM, RANKL is increased, OPG is decreased, resulting in increased osteoclast activity

Front 47

In monoclonal gammopathy of undetermined significance (MGUS), How are the proteins, clonal cells, others?

Back 47

In monoclonal gammopathy of undetermined significance (MGUS), the monoclonal protein is <30 g/l with <10% bone marrow clonal cells and no evidence of multiple myeloma, other B-cell proliferative disorders or amyloidosis

Front 48

Which is the most common serum onoclonal antibody in MM?

Back 48

IgGkappa

Front 49

Diagnosis and investigation
of MM?

Back 49

Patients typically present with bone pain, renal impairment, anemia, or a combination of these
Myeloma should also be considered in patients with unexplained backache, loss of height, or radiologic evidence of osteoporosis, recurrent bacterial infection

Front 50

What staging sytem (not the international one) is used for MM? What is it based on?

Back 50

In the Durie-Salmon Staging System, the clinical stage of disease (Stage I, II, or III) is based on several measurements, including levels of M protein, the number of bone lesions, haemoglobin values, and serum calcium levels. Stages are divided further according to kidney function, which is determined by serum creatinine levels (classified as A or B)

Front 51

What is the internatioanl staging system of MM based on?

Back 51

A combination of serum b2-microglobulin and serum albumin provided a simple, powerful, and reproducible 3-stage classification

Front 52

Treatment.. Do not understand it.

Back 52

Treatment.. Do not understand it.