Leukemias and blood intro

Question 1

What are the two main cell lineages from a pluripotent haematopoietic stem cell?

Answer 1

Myeloid stem cell
Lymphoid stem cell

Question 2

What are the different cell lineages that develop from a lymphoid stem cell?

Answer 2

B cell
T cell
Natural killer cell

Question 3

What are the different cell lineages that develop from a myeloid stem cell?

Answer 3

1. Myeloblast:
   - basophils, neutrophil, eosinophil, monocyte (macrophage)
2. Megakaryocytes -> platelet
3. Erythrocyte to rbcs

Question 4

Define leukemia

Answer 4

A cancer of the bone marrow - that affects a particular line of stem cells -> unregulated production of single type of abnormal wbc
Suppression of other cell lines

Question 5

What is panctyopenia? Related to leukaemia

Answer 5

Pancytopaenia - low RBCs, Low WBCs, low platelets
Appears in leukemia when one type of abnormal white blood cell is produced greatly and all other cell types are greatly suppressed.

Question 6

What are the different types of leukemia?

Answer 6

Acute lymphoblastic leukaemia
Acute myeloid leukaemia
Chronic lymphocytic leukaemia
Chronic myeloid leukaemia

Question 7

What is acute lymphoblastic leukarmia?

Answer 7

Affects lymphocyte precursor cells causing acute proliferation of a single type of lymphocyte - usually a B cell.
Replaces other cell types in bone marrow causing a pancytopaenia

Question 8

What is the key epidemiology of acute lymphoblastic leukaemia?

Answer 8

Most common in children <5yrs but can affect adults
Most common childhood malignancy
Associated with Down syndrome

Question 9

What is acute myeloid leukaemia?

Answer 9

Immature myeloblasts (myeloid lineage) accumulate abnormally
Many subtypes
Usually results from transformation from a myeloproliferative disorder.

Question 10

What is the eky epidemiology of acute myeloid leukaemia?

Answer 10

Can present at any age, but usually middle age and onwards

Question 11

What are the key diagnostic findings in acute myeloid leukaemia?

Answer 11

Blood film and bone marrow biospy - high proportion of blast cells
Auer rods - in cytoplasm of blast cells.

Question 12

What is chronic lymphocytic leukaemia?

Answer 12

Slow proliferation of a single type of more mature lymphocytes (usually B)
Tend to be partially differentiated by function abnormally and accumulate over time.

Question 13

What is the key presentation of CLL?

Answer 13

Usually adults 60-70yrs and asymptomatic
In symptoms - recurrent infections, anaemia, bleeding and weight loss.

Question 14

What is a complication of chronic lymphocytic leukaemia?

Answer 14

Richters transformation: CLL to high grade B cell lymphoma
May also cause warm autoimmune haemolytic anaemia

Question 15

What are the signs of chronic lymphocytic leukaemia on blood film?

Answer 15

Smear or smudge cells = ruptured WBCs

Question 16

What cell lineage tends to be affected in chronic myeloid leukaemia?

Answer 16

From mature myeloid cells - mainly affects granulocytes

Question 17

What are the different phases of CML?

Answer 17

1. Chronic - asymptomatic, several yrs, incidental raised wcc
2. Accelerated
3. Blast phases

Question 18

What are the features of the accelerated phase of chronic myeloid leukaemia?

Answer 18

Abnormal blasts =>20% blasts
Symptomatic = anaemia, thrombocytopaenia and immunodeficiency

Question 19

What are the features of the blast phase of CML?

Answer 19

Most severe phases
high proportion greater than >20% blast cells are abnormal
Severe symptoms and pancytopenia is often fatal

Question 20

What is the key risk factor for chronic myeloid leukaemia?

Answer 20

Philadelphia chromosome

Question 21

What is the mutation seen in the Philadelphia chromosome?

Answer 21

Reciprocal translocation between chromosomes 9 and 22.

Question 22

What is the general presentation of leukaemia?

Answer 22

Fatigue
Fever
Pallor due to anaemia
Petechiea due to thrombocytopaenia
Abnormal bleeding/bruising
Lymphadenopathy
Hepatosplenomegaly
Failure to thrive (children)

Question 23

What are the different types of bruising seen in leukemia?

Answer 23

All are non-blanching lesions caused by bleeding under the skin
Petechiae - less than 3mm
Purpura - less than 10mm
Echymosis - large, flat more than 10mm.

Question 24

What are the key NICE recommendations for the diagnosis of leukemia?

Answer 24

Urgent FBC within 48hrs for everyone
Children with petechiae or hepatosplenomegaly are sent for immediate specialist assessment.

Question 25

What are the typical investigations for diagnosis of leukemia?

Answer 25

Bedside - bone marrow and lymph node biospy
Bloods - FBC, Blood film, LDH
Imaging - CT and PET for staging
Other - genetic tests and immunophenotyping (treatment and prognosis)

Question 26

What are the key features of a bone marrow biopsy?

Answer 26

Usually taken from the iliac crest
Involves local anaesthetic and a special needle.
Bone marrow aspiration - a liquid sample of cells
Bone marrow trephine - solid core sample, better assessment of cells and structure

Question 27

What is the general management for leukemia?

Answer 27

MDT - oncology and haematology
Mainly - chemo and tarted therapies
May also offer radiotherapy, bone marrow transplant and surgery.

Question 28

What are some examples of targeted therapies used in CLL?

Answer 28

Tyrosine kinas inhibitors - ibrutinib
Monoclonal antibodies - rituximab to target B cells.

Question 29

What is tumour lysis syndrome?

Answer 29

Chemicals released when cells are destroyed by chemo.
High uric acid, K+, PO4-
Low calcium (due to high PO4-)

Question 30

What are some complications of tumour lysis syndrome?

Answer 30

AKI
Cardiac arrhythmias
Seizures
Lactic acidosis