Acute Leukaemias, Pre-Leukaemic Conditions and Chronic Leukaemias

Question 1

What is myelodysplastic syndrome (MDS) and how is it managed?

Answer 1

• Clonal blood disorder characterised by failure of effective erythropoiesis (Low blood counts)
• More common in the elderly and patients with previous chemotherapy or radiotherapy
• Causes low levels of blood components in the myeloid line (i.e. anaemia, neutropenia, thrombocytopenia)
• Increased risk of transforming into AML
• May be asymptomatic or present with symptoms of anaemia, neutropenia or thrombocytopenia.
• Diagnosis:
  
  • FBC
  • Blasts on blood film
  • Bone marrow aspiration and biopsy for diagnosis
• Management:
  
  • Watchful waiting
  • Supportive treatment with blood transfusions
  • Chemotherapy
  • SCT

Question 2

What are myeoproliferative disorders (MPDs) and how are they managed?

Answer 2

• Uncontrolled proliferation of a single type of stem cell
• Systemic symptoms include:
  
  • Fatigue
  • Weight loss
  • Night sweats
  • Fever
• Main types include:
  
  • Essential thrombocythaemia (↑ platelets)
  • Polycythaemia vera (↑ RBCs/platelets/WBCs)
  • Myelofibrosis (↑ fibrous tissue/platelets/WBCs)
• Clonal blood disorders where the JAK2, MPL and CALR genesare present
• Diagnosis through bone marrow biopsy and testing for JAK2, MPL and CALR genes
• Management of myelofibrosis:
  
  • Monitoring if mild symptoms
  • Allogenic SCT
  • Chemotherapy
  • Supportive management
• Management of polycythaemia vera:
  
  • Venesection
  • Aspirin (reduce risk of clot formation)
  • Chemotherapy
• Management of essential thrombocytopenia:
  
  • Aspirin (reduce risk of clot formation)
  • Chemotherapy
• Risk of transformation to AML.

Question 3

Acute Myeloid Leukaemia (AML)

Answer 3

• Most common acute leukaemia in adults
• Can be result of transformation of MPD
• Symptoms include:
  
  • Lethargy
  • Infection
  • Bleeding and bruising
  • Bone pain
  • Gum swelling
  • Lymphadenopathy
  • Skin rash
• Investigations will show:
  
  • Anaemia
  • Neutropenia
  • Thrombocytopenia
  • Blasts cells on blood film that can have rods in their cytoplasm called auer rods

Question 4

Acute Lymphoid Leukaemia (ALL)

Answer 4

• Most common leukaemia in children - the limping child
• Associated with Down syndrome
• Acute proliferation of a single type of lymphocyte - usually B lymphocytes, which replace other types of cells leading to pancytopenia
• Presents with:
  
  • Purpuric rash
  • Unexplained bone pain
  • Lumps vs liquid (lymphoblastic lymphoma vs true ALL)
• Blood film will show blast cells.

Question 5

Chronic Myeloid Leukaemia (CML)

Answer 5

• Three phases:
  
  • Chronic phase - lasts around 5 years, asymptomatic, raised WCC
  • Accelerated phase - abnormal blast cells take up high proportion of bone marow and patients become symptomatic
  • Blast phase - even higher proportion of blast cells (>30%), severe symptoms and often fatal
• Presentation:
  
  • May be asymptomatic
  • Fatigue
  • Weight loss
  • Night sweats
  • Abdominal discomfort
  • Splenomegaly
• Cytogenetic change is the Philadelphia chromosome (translocation between chromosome 9 and 22 - BRC-ABL)

Question 6

Management of leukaemia

Answer 6

• Primarily treated with chemotherapy and steroids
• CML also uses Imatinib - blocks downstream target of phosphorylation]
• CLL also uses alkylating agents, purine nucleosides and chemoimmunotherapy

Question 7

Chronic Lymphocytic Leukaemia (CLL)

Answer 7

• Most common leukaemia in adults overall
• Chronic proliferation of single type of well differentiated lymphocytes - usually B lymphocytes
• Often asymptomatic but can present with warm AHIA
• CLL can transform into high-grade lymphoma called Richter’s transformation
• Blood film shows smear or smudge cells
• CD 5, 19, 20, 23 positive
• Bone marrow shows nodular or diffuse infiltrate
• Flow cytometry also used
• Presentation:
  
  • May be asymptomatic
  • Lethargy
  • Night sweats
  • Weight loss
  • Symptoms of anaemia
  • Lymphadenopathy
  • Infection
• Staging uses BINET
  
  • A <3 involved nodes (10yrs)
  • B > 3 involved nodes, liver, spleen (7yrs)
  • C - anaemia or thrombocytopenia (2 yrs)

Question 8

Ages of presentation for leukaemia (remember ALL CeLLmates have CoMmon AMbitions)

Answer 8

• Under 5 and over 45 – acute lymphoblastic leukaemia (ALL)
• Over 55 – chronic lymphocytic leukaemia (CeLLmates)
• Over 65 – chronic myeloid leukaemia (CoMmon)
• Over 75 – acute myeloid leukaemia (AMbitions)

Question 9

Tumour lysis syndrome

Answer 9

• Caused by release of uric acid from cells being destroyed by chemotherapy
• Can form crystals in intestinal tissue and tubules of kidneys leading to AKI