Myelodysplastic Syndromes (MDS)and Acute Myeloid Leukaemia (AML

Question 1

define myelodysplatic syndromes

Answer 1

myelo- marrow
dysplastic- abnormal or funny looking

Question 2

describe myelodysplatic syndromes ( L)

Answer 2

-proportion of leukaemia cells or blasts <20% nucleated cels in bone marrow
=Bone marrow cells fail to make adequate numbers of healthy blood cells
i.e. both quantity and quality (function) of cells are affected
-Abnormal cells crowd out remaining normal cells

Question 3

what is can myelodysplatic syndromes progress to?

Answer 3

acute myeloid leukaemia

Question 4

What is Acute Myeloid Leukaemia?

Answer 4

Acute myeloid leukaemia (AML) is a heterogeneous clonal malignancy characterised by
-immature myeloid cell proliferation (defined as ≥20% “blasts”)
and
-bone marrow failure

Question 5

describe the epidemiology of MDS

Answer 5

4.5 in 100,000
Median age at diagnosis = 76 years

Question 6

describe the epidemiology of AML

Answer 6

less than 1% each year
age 85-89

Question 7

what are the diagnostic features of MDS in a full blood count blood test? ( L)

Answer 7

Low blood counts
-red cells (symptoms include fatigue, shortness of breath, lightheadedness)
-white cells (symptoms include increased risk of frequent and/or severe infections)
-platelets (bleeding/ bruising)

-Peripheral blood film demonstrates dysplastic features (e.g. hypogranular neutrophils, platelet anisopoikilocytosis, blasts)

Question 8

what are the diagnostic features of AML in a full blood count blood test?

Answer 8

White cell counts can be
-Low
-Normal
-High
-symptoms include increased risk of frequent and/or severe infections (because a large proportion of the white cells are abnormal)

-Other blood parameters are usually low
–red cells (symptoms include fatigue, shortness of breath, lightheadedness)
-platelets (symptoms of bleeding/ bruising)

Question 9

What are the potential differential diagnoses

Answer 9

B12/ folate or mixed haematinic deficiency
Infection (e.g. retroviral disease, herpesvirus)
Medications
Autoimmune
Liver disease (e.g. cirrhosis)
post operative
severe sepsis- Blasts in peripheral blood usually associated with neutrophil

Question 10

in a patient with suspected MDS/AML what investigations should you do?

Answer 10

-A good history
-Review of previous blood test results
—Was the FBC previously normal?
–Has the Hb/ WC/ neutrophils/ platelet counts been downward trending for some weeks/ months/ years?
-FBC and blood film
-Haematinics (B12, folate, ferritin)

Question 11

when should you be concerned? ( L)

Answer 11

-There are blasts on peripheral blood
-The deterioration in FBC parameters is very rapid (days/ weeks)
-Have a low threshold for all other patients to repeat FBC in 1-2 weeks and tell them to ring if they notice any new symptoms (i.e. symptomatic anaemia, infection, bleeding/ bruising)

Question 12

how do you diagnose MDS and AML

Answer 12

Blood tests (full blood count & blood film)
Bone marrow aspirate and trephine biopsy

Question 13

What is morphology?

Answer 13

= the appearance of cells on slides

Question 14

in morphology what are the requirements for myelodysplastic syndrome?

Answer 14

Requirement of 10% dysplasia in any cell line(s)
Blast % can be anywhere from 0 – 19%

Question 15

in morphology what are the requirements for acute myeloid leukaemia syndrome?

Answer 15

minimum 20% blasts

Question 16

define leukemia

Answer 16

malignant proliferation of haemopoietic cells

Question 17

what history is relevant when diagnosing leukaemia ?

Answer 17

-Anaemia
—–Fatigue
——Shortness of breath
-Infection
—–Tonsillitis
—–Fevers/ rigors
-Thrombocytopenia
–Bruising
–Bleeding – mucosal usually
–Rash
Low haemoglobin
Low platelets
Very low neutrophils
Blast cells present with Auer rods = acute myeloid leukaemia

Question 18

what tests do you do/ what do you look at to diagnose patients?

Answer 18

-Blood tests (morphology, cytogenetics, minimal residual disease monitoring, molecular genetics, deep sequencing, multi-parameter flow cytometry)

-Bone marrow aspirate and trephine biopsy

-Increase in blasts >20% (acute leukaemia)

-Background abnormalities to suggest pre-existing bone marrow abnormalities
-Cytogenetics for prognosis
-Molecular genetics for prognosis
-Immunophenotyping

Question 19

describe the onset of Chronic myeloid leukaemia

Answer 19

slow

Question 20

describe Chronic myeloid leukaemia film

Answer 20

left shift+ basophilia

Question 21

describe the Chronic myeloid leukaemia WCC

Answer 21

in a FBC- high WCC

Question 22

what is a key diagnostic feature of Chronic myeloid leukaemia

Answer 22

Philadelphia chromosome

Question 23

what treatments are used in Chronic myeloid leukaemia

Answer 23

arget molecular therapy – tyrosine kinase inhibitors: Imatinib

AML treatment
Chemotherapy and supportive measures
Take into account – age, fitness, comorbidities, AML features, clinical trials

Question 24

what is the Most common paediatric malignancy?

Answer 24

Acute lymphoblastic leukaemia

Question 25

describe the acute presentation of Acute lymphoblastic leukaemia

Answer 25

bone marrow failure organ infiltration (cns)

Question 26

how is Acute lymphoblastic leukaemia diagnosed?

Answer 26

Diagnosis – as for AML philadelphia chromosome

Question 27

what does It mean if the Philadelphia chromosome is present?

Answer 27

poor prognosis

Question 28

describe the treatment phases

Answer 28

1.Induction 2.Consolidation 3.Delayed intensification 4.Maintenance

Question 29

what are all the treatments?

Answer 29

- treatment phases - CNS directed therapy - Stem cell transplant

Question 30

what is the most common leukaemia?

Answer 30

Chronic lymphocytic leukaemia

Question 31

describe Chronic lymphocytic leukaemia

Answer 31

- has a gradual accumulation of B lymphocytes - blood/bone marrow - lymph glands - including spleen

Question 32

how is Chronic lymphocytic leukaemia usually found?

Answer 32

incidentally on FBC

Question 33

describe the epidemiology of Chronic lymphocytic leukaemia

Answer 33

Generally elderly but 20% <55yrs

Question 34

describe the clinical course of Chronic lymphocytic leukaemia

Answer 34

- variable - progressive lymphadenopathy/ hepatosplenomegaly - auto immune- haemolysis, ITP - bone marrow failure- due to marrow replacement

Question 35

what treatment is done for Chronic lymphocytic leukaemia

Answer 35

Do nothing Chemotherapy monoclonal antibodies Targeted therapy Bone marrow transplant

Question 36

what does chemotherapy do?

Answer 36

causes damage preferentially to rapidly dividing cells

Question 37

what is used for chemotherapy ?

Answer 37

Combinations of drugs are commonly used

Question 38

why does dosing of drugs have to be carefully managed in chemotherapy?

Answer 38

to optimise balance between: -Destroying leukemic cells -Not causing irreversible toxicity to other normal cells

Question 39

what are other things to consider pre- chemo?

Answer 39

supportive measures- Fertility cryopreservation clinical trial availability

Question 40

what are the side effects of chemo ?

Answer 40

-Nausea -Cytopenias -Anaemia -Neutropenia -Low platelets and risk of bleeding/ -bruising -Bystander organ damage (kidneys, liver, etc) -Temporary hair loss