Symposium 2 - Leukaemia

Question 1

Complete the diagram on haematopoiesis

Answer 1

Question 2

What is G-CSF?

Answer 2

G-CSF promotes neutrophil proliferation
G-CSF = granulocyte colony stimulating factor

Question 3

What is cancer?

Transformed cell phenotype?

Genetic?

Epigenetic?

Answer 3

Transformed cell phenotype

–Uncontrolled proliferation

–Failure to undergo apoptosis

Genetic

–Oncogenes

–Tumour suppressor genes

Epigenetic

–Dysregulated gene expression

–Aberrant DNA methylation

Question 4

Complete the diagram on types of DNA mutation

Answer 4

Question 5

What are the clinical features of leukaemia?

Answer 5

Myelofibrosis (causes massive splenomegaly)

Polycythemia rubra vera (too many red cells)

Essential thrombocythemia (too many platelets)

Question 6

What does this blood smear show?

Answer 6

1. Polycythemia rubra vera
2. Myelofibrosis

Question 7

What does this blood smear show?

Answer 7

Leucoerthyroblastic blood picture

Nucleated RBC and immature leucocytes

Question 8

What is JAK-STAT signalling?

Answer 8

Signal transduction pathway for EPO and G-CSF

Question 9

What signalling pathway is mutated in the majority of acute myeloid leukaemia cases?

Answer 9

JAK-STAT signalling
Signal transduction pathway for EPO and G-CSF

Question 10

Complete the diagram

Answer 10

Question 11

Why does myelofibrosis cause splenomegaly?

Answer 11

When bone marrow becomes fibrotic, spleen takes over

Question 12

What is myelofibrosis?

Answer 12

Fibrotic bone marrow

Question 13

What is a myeloproliferative state?

Answer 13

Overproduction of a type of blood cell

Question 14

Whats the diagnosis?

Answer 14

Too many white cells - chronic myeloid leukaemia

Question 15

What chromosome is associated with chronic myeloid leukaemia?

Answer 15

“Philadelphia chromosome”

Chromosome 22->9

t(9;22) translocation

BCR gene from chromosome 22 and ABL gene from chromosome 9 come together.

Question 16

What test is this?

Answer 16

“FISHing” for CML
FISH = fluorescent in situ hybridisation

Question 17

What does imatanib target?

Answer 17

The BCR-ABL oncogene

Question 18

What effect does imatinib have on chronic myeloid leukaemia patients?

Answer 18

Normalises blood counts

Improves survival in CML

Question 19

Which leukaemia can occasionally turn into AML?

Answer 19

CML

Question 20

What is acute myeloid leukaemia?

Answer 20

Uncontrolled proliferation of primitive cells in the bone marrow

Question 21

Name 3 causes of bone marrow failure in acute myeloid leukaemia

Answer 21

–Anaemia

–Infections

–Bleeding

Question 22

What does this show?

Answer 22

AML

Leukaemic blasts - very high nucleus:cytoplasm ratio

Question 23

What are the clinical features of AML?

Answer 23

1. Anaemia
2. Infections
3. DIC
4. Ulcers
5. Infiltration
6. Bruising

Question 24

What are the 5 ways of diagnosing AML?

Answer 24

1. Morphology - blood film
2. Immunophenotyping
3. Genetic
4. Cytogenetic
5. Molecular

Question 25

What are the 3 treatments for AML?

Answer 25

Chemotherapy – kills rapidly dividing cells: Supportive therapy: –Antibiotics, antifungals –Transfusions of blood and platelets Allogeneic stem cell transplantation:

Question 26

What are the steps for the donor and recipient in a allogeneic stem cell transplant?

Answer 26

Question 27

What are the 2 options for an allogenic stem cell transplant donor?

Answer 27

Sibling (1-in-4 chance of being a match) Matched unrelated donor (Anthony Nolan

Question 28

What chemotherpy is used for AML?

Answer 28

–Combination regimes –Myelo-ablative cycles of treatment

Question 29

What 3 supporting measures are needed for AML patients?

Question 30

How would you manage a patient with neutropenic sepsis?

Answer 30

MEDICAL EMERGENCY – High risk of death * Blood cultures and blind antibiotic therapy if fever \> 38°C 1st line – Tazocin (Piperacillin/Tazobactam) +/- Gentamicin 2nd line – Switch to Meropenem +/- Teicoplanin (for Gram +ve) 3rd line – Add anti-fungal e.g. Ambisome (Amphotericin) Resuscitate patient with i.v. fluids if hypotensive May require inotropic support on ITU

Question 31

In neutropenic sepsis are gram positive or gram negative bacteria more dangerous?

Answer 31

Gram negative

Question 32

What type of pneumonia can AML patients develop?

Answer 32

Pneumocystis pneumonia

Question 33

What is graft vs host disease? (acute/chronic)

Answer 33

* Caused by donor/host mismatches in major and minor HLA loci * Results in acute GVH (\<100 days) and chronic GVH (\>100 days) post-transplant

Question 34

How is graft vs host disease prevented?

Answer 34

–T-cell depletion of infused donor cells (graft) –Immunosuppression of recipient (ciclosporin)

Question 35

What are the clinical manifestations of graft vs host disease?

Answer 35

–Skin rash, sometimes severe –Diarrhoea, can be bloody –Deranged liver function, can lead to liver failure

Question 36

What is graft vs leukaemia?

Answer 36

•Graft-vs-leukaemia effect is how the stem cell transplant cures leukaemia

Question 37

\_\_\_\_\_\_\_\_\_\_\_\_\_ post-Tx can treat relapse by augmenting GVL effect

Answer 37

Donor lymphocyte infusions (DLI)

Question 38

What mutation occurs as a young baby but takes years to cause AML?

Answer 38

DNMT3A methyltransferase