Malignant Haematology - Acute & Chronic Leukaemia

Question 1

Define leukaemia [1]

Answer 1

malignant neoplasms of cells derived from haemopoietic stem cells characterised by diffuse replacement of bone marrow with unregulated, proliferating neoplastic cells which usually enter the blood

Question 2

What are the characteristics of Myelodysplastic Syndrome (MDS)? [5]

Answer 2

• Clonal blood disorder characterised by:
  
  1. dysplastic blood and marrow appearances
  2. marrow failure
  3. ineffective haemopoiesis in at least one myeloid line
  4. low blood counts

Question 3

What are Myeloproliferative Disorders (MPDs)? [3]

Answer 3

Clonal blood disorders associated with the JAK2 mutation characterised by uncontrolled clonal proliferative of one or more of the cell lines in bone marrow

Question 4

Give 3 examples of myeloproliferative disorders and the characteristics of each [6]

Answer 4

1. Essential Thrombocythemia
   
   • too many platelets
2. (Primary) Polycythaemia Vera
   
   • too many red cells (+plts +WC)
3. Myelofibrosis
   
   • too much fibrous tissue and scarring in bone marrow
   • → due to increased fibroblast stimulating factors from megakaryocytes (+plts +WC))

Question 5

What are the types of acute leukaemias? [7]

Answer 5

1. acute myeloid leukaemia
   
   • erthryoleukaemia
   • monocytic leukaemia
   • megakaryocytic leukaemia
2. acute lymphoblastic leukaemia
   
   • T-lymphoblastic leukaemia
   • B-lymphoblastic leukaemia

Question 6

What are the possible causes of acute leukaemias? [7]

Answer 6

1. Largely unknown
2. Chemicals
3. Chemotherapy
4. Radiotherapy
5. Genetic
   
   • Down’s Syndrome
   • Fanconi Syndrome
6. Antecedent blood disorders (MDS, MPD)
7. Viruses?

Question 7

What are the typical signs & symptoms of acute leukaemia? [8]

Answer 7

1. Rapid onset of symptoms
2. Lethargy
3. Infection
4. Bleeding and bruising
5. Bone pain
6. Gum swelling
7. Lymphadenopathy,
8. Skin rash

Question 8

What investigations would you carry out in a patient with suspected acute leukaemia and what abnormalities would you expect for each investigation? [12]

Answer 8

1. Blood film
   
   • Anaemia
   • Neutropenia
   • Thrombocytopaenia
   • Abnormal lymphoid or myeloid blast cells
2. Bone marrow aspirate
   
   • Increased cellularity
   • Abnormal lymphoid or myeloid blast cells
3. FBC
   
   • Anaemia
   • Increased WCC
   • Thrombocytopenia (low platelet count)

Question 9

What are the management options for acute myeloid leukaemia? [4]

Answer 9

1. Intensive chemotherapy +/- stem cell transplant (SCT)
   
   • Anthracycline and cytarabine based chemotherapy
   • Heavy myelotoxicity
2. Low Dose chemotherapy
3. Supportive care only
4. Some only curable using allogenic transplant

Question 10

What does supportive treatment for acute myeloid leukaemia involve? [6]

Answer 10

1. Blood transfusion
   
   • Symptomatic patients
   • Improves quality of life
2. Fresh frozen plasma
   
   • for coagulopathy/DIC
3. Platelet transfusion
   
   • purpura and bleeding
   • during fever, sepsis, DIC
4. Antibiotics
5. Growth Factors (G-CSF)
6. Granulocytes
   
   • Refractory infections

Question 11

What are the management options of acute lymphoblastic leukaemia? [3]

Answer 11

1. Chemotherapy
   
   • Prednisolone, cyclophosphamide, anthracycline, asparaginase, vincristine, etoposide, cytarabine based chemo
2. CNS directed treatment essential
3. Initial aggressive therapy, then oral maintenance (1-2 years)

Question 12

What is allogenic transplant? [1]

Answer 12

transplantation of HLA matched stem cells from either sibling or unrelated donor

Question 13

What is GvHD and GvL in allogenic transplantation and what is the challenge associated with this? [7]

Answer 13

1. Graft versus Host Disease (GvHD)
   
   • After allogeneic transplant - new donor’s immune system recognises the host body as foreign and starts to attack it
   • Manifests as skin rash, jaundice, diarrhoea
   • Two different types:
     
     • Acute GvHD – within 100 days
     • Chronic GvHD – after first 100 days
   • Treated with immunosuppressive agents e.g. cyclosporin
2. Graft versus leukaemia (GvL)
   
   • The same cells which cause GvHD also attack the remaining leukaemia cells
   • GvL is very effective, especially in patients where a good remission has been hard to maintain
3. Challenge is to minimise GvHD and maximise GvL

Question 14

Who more commonly gets chronic lymphocytic leukaemia? [2]

Answer 14

1. more common in males
2. incidence increases with age

Question 15

What is chronic B lymphocytic leukaemia? [1]

Answer 15

Neoplastic proliferation of mature naïve B cells that have escaped programmed cell death and co-express CD5&20

Question 16

Describe the BINET Staging System used to stage chronic lymphocytic leukaemia (CLL) [3]

Answer 16

1. Stage A: <3 involved nodes
2. Stage B: >3 involved nodes, liver and spleen
3. Stage C: Anaemia or thrombocytopenia

Question 17

Define chronic myeloid leukaemia (CML) [1]

Answer 17

Neoplastic proliferation of mature myeloid cells

Question 18

What is the genetic basis of chronic myeloid leukaemia? [2]

Answer 18

Chromosome 22 (BCR) translocated to chromosome 9 (AB1)

• Produces the Philadelphia chromosome (BCR-ABL)

Question 19

What are the typical symptoms of chronic myeloid leukaemia? [6]

Answer 19

1. May be asymptomatic (20-50%)
2. Symptoms:
   
   • Fatigue
   • Weight loss
   • Night sweats
   • Abdominal discomfort
   • Splenomegaly

Question 20

What are the typical histological features of chronic myeloid leukaemia? [5]

Answer 20

1. Excessive cell proliferation at the level of myeloblast
2. Increased number of granulocytes
   
   • Neutrophils
   • Basophils
   • Eosinophils