Concepts of Malignant Haematology

Question 1

What are the progeny of myeloid precursors?

Answer 1

Erythrocytes, platelets, granulocytes, macrophages

Question 2

What are the progeny of lymphoid precursors?

Answer 2

Dendritic cells, T cells, NK cells, B cells

Question 3

What methods can be used to identify mature myeloid cells?

Answer 3

Morphology, cell surface antigens (e.g glycophorin A for red cells), enzyme expression (e.g myeloperoxidase for neutrophils)

Question 4

What is malignant haemopoiesis characterised by?

Answer 4

Increased numbers of abnormal and dysfunctional cells

Loss of normal function (e.g haemopoiesis)

Question 5

What are the underlying mechanisms of malignant haemopoiesis?

Answer 5

Due to one or more of the following = increased proliferation, lack of differentiation, lack of maturation, lack of apoptosis

Question 6

What occurs in acute leukaemia?

Answer 6

Proliferation of abnormal progenitors with block in differentiation/maturation

Question 7

What does normal cells being replaced by abnormal ones in acute leukaemia cause?

Answer 7

Loss of normal haemopoiesis and subsequent failure of blood and bone marrow

Question 8

What occurs in chronic myeloid leukaemia?

Answer 8

Proliferation of abnormal progenitors but no block in differentiation/maturation

Question 9

What does high power microscopy of chronic myeloid leukaemia show?

Answer 9

Wide variety of cell types and neutrophils

Question 10

What causes haematological malignancy?

Answer 10

Genetic, epigenetic and environmental interaction
Acquired somatic mutation in regulatory genes
Recurrent cytogenetic abnormalities

Question 11

What are driver mutations?

Answer 11

Acquired somatic mutations that are actively involved in cancer pathogenesis

Question 12

What are passenger mutations?

Answer 12

Acquired somatic mutations that don’t confer growth advantage but are present in ancestors of cancer cell when they acquired its driver mutation

Question 13

How important are recurrent cytogenetic abnormalities in causing haematological malignancy?

Answer 13

Usually contribute to cancer pathogenesis but are not causative

Question 14

What ability allows driver mutations to cause cancer?

Answer 14

Have ability to select clones = confer growth advantage on cells and are selected during cancer evolution

Question 15

What are clones?

Answer 15

Population of cells derived from a single parent cell = can diversify but share similar genetic backbone

Question 16

Why is the parent cell of clones important?

Answer 16

Contains genetic marker that is shared by daughter cells

Question 17

How does normal haemopoiesis differ from malignant haemopoiesis?

Answer 17

Normal haemopoiesis is polyclonal whereas malignant haemopoiesis is usually monoclonal

Question 18

What is the classification of haematological malignancy based on?

Answer 18

Lineage = myeloid or lymphoid
Developmental stage within lineage
Anatomical site

Question 19

What does the term lymphoblastic suggest?

Answer 19

A defect in primitive cells

Question 20

What parts of the body does leukaemia involve?

Answer 20

Blood

Question 21

What parts of the body are involved in lymphoma?

Answer 21

Lymph node involvement with lymphoid malignancy

Question 22

Why is chronic lymphocytic anaemia difficult to classify by site?

Answer 22

It can involve both blood and lymph nodes

Question 23

What is myeloma?

Answer 23

Plasma cell malignancy of marrow

Question 24

How can haematological malignancies by classified by their histology?

Answer 24

Aggressive = acute leukaemia, high grade lymphoma

Less aggressive = chronic leukaemia, low grade lymphoma

Question 25

What are some features of histological aggression?

Answer 25

Large cells with high nuclear-cytoplasmic ratio Prominent nuclei Rapid proliferation

Question 26

What do acute leukaemias usually present with?

Answer 26

Failure of bone marrow

Question 27

What cells are affected by chronic myeloid leukaemia and myeloproliferative neoplasms?

Answer 27

More primitive progenitors (e.g stem cells)

Question 28

What cells are mostly affected by acute leukaemias?

Answer 28

Acute myeloid = multipotent progenitors | Acute lymphoid = lymphoid progenitors

Question 29

What cells are affected by chronic lymphoid leukaemia?

Answer 29

B cells

Question 30

What is acute leukaemia?

Answer 30

Rapidly progressive clonal malignancy of marrow/blood with maturation defects = decrease/loss of normal haemopoietic reserve

Question 31

What is acute leukaemia defined as?

Answer 31

Excess of blasts (>=20%) in either peripheral blood or bone marrow

Question 32

What are the types of acute leukaemia?

Answer 32

Myeloid and lymphoid

Question 33

What is acute lymphoid leukaemia?

Answer 33

Disease of primitive lymphoid cells = most common childhood cancer

Question 34

What are the features of acute lymphoid leukaemia?

Answer 34

Anaemia, infection, bleeding, bone pain High count with obstruction of circulation Often extra-haematological involvement = CNS, testes

Question 35

What is the epidemiology of acute myeloid leukaemia?

Answer 35

More common in elderly = age >60 | May be de novo or secondary

Question 36

What are the features of acute myeloid leukaemia?

Answer 36

Presents similar to acute lymphoid leukaemia but with more prominent symptoms of anaemia

Question 37

What are the subtypes of acute myeloid leukaemia?

Answer 37

Coagulation defect = DIC in acute promyelocytic leukaemia | Gum infiltration

Question 38

What investigations are done of acute leukaemia?

Answer 38

Blood count and film plus coagulation screen Bone marrow aspirate for morphology Cytogenetic analysis for prognosis

Question 39

What test is diagnostic for acute leukaemia?

Answer 39

Immunophenotyping = distinguishes between acute myeloid and lymphoid leukaemias

Question 40

What test can be done when bone marrow aspirate is suboptimal?

Answer 40

Trepine sample = small piece of bone sample

Question 41

What are the features of blood film for acute leukaemia?

Answer 41

Reduction in normal cells | Presence of blasts with high nuclear:cytoplasmic ratio

Question 42

What is a blood film feature of acute myeloid leukaemia?

Answer 42

Aver rods = granulations on blood film

Question 43

What is the mainstay of treatment for acute leukaemia?

Answer 43

Multi-agent chemotherapy

Question 44

What is the treatment programme for acute lymphoid leukaemia?

Answer 44

Lasts 2-3 years = different phases of varying intensity, targeted treatment in certain subsets

Question 45

What is the treatment programme for acute myeloid lymphoid?

Answer 45

2-4 cycles of chemo = 5-10 days of chemo followed by 2-4 weeks of recovery Prolonged hospitalisation with some targeted treatment

Question 46

What is a Hickman line?

Answer 46

Allows for long term venous access for drug administration = tip sits at junction of IVC and right atrium

Question 47

What haematological issues are associated with marrow suppression?

Answer 47

Anaemia, neutropenia, thrombocytopenia

Question 48

What is a life threatening complication of neutropenia in chemotherapy patients?

Answer 48

Gram negative sepsis = start broad spectrum antibiotics in presence of neutropenic fever while waiting for culture results

Question 49

What are the complications of chemotherapy?

Answer 49

Nausea/vomiting, hair loss, liver/renal dysfunction, tumour lysis syndrome (1st course of treatment), infection, loss of fertility, cardiomyopathy

Question 50

When should anti-fungals be started in a patient undergoing chemotherapy?

Answer 50

Prolonged neutropenia and persisting fever unresponsive to anti-bacterial agents

Question 51

What prophylactic treatment is offered to patients with acute lymphoid leukaemia?

Answer 51

Prophylaxis for pneumocystis pneumonia

Question 52

How long does it take for bone marrow function to recover if chemotherapy has been successful?

Answer 52

4-6 weeks

Question 53

What is the prognosis of acute leukaemia?

Answer 53

Childhood lymphoid = >85-90% Adult lymphoid = 30-40% Adult myeloid age 60 = 10% or less