Concepts in Malignant Haematology & Acute leukaemia

Question 1

name the 5 stages of normal haemopoiesis

Answer 1

Self renewal
Proliferation
Differentiation or lineage commitment 
Maturation
Apoptosis

Question 2

how do we identify progenitors/stem cells?

Answer 2

immunophenotyping using surface antigens

Question 3

why happens in malignant haemopoisis? (4)

Answer 3

increased proliferation
Failure of differentiation
Lack of maturation
lack of apoptosis

therefore get increased no.s of dysfunctional cells and may have loss of the normal haemopoietic reserve

Question 4

Describe what bone marrow looks like in acute leukaemia?

Answer 4

overrun by mononuclear, monotonous cells, proliferating aggressively but not maturing

Question 5

what causes haematological malignancy?

-describe the difference between driver and passenger mutations?

Answer 5

genetic, epigenetic and environmental interaction

somatic mutations in regulatory genes (driver vs passenger)

recurrent cytogenic abnormalities e.g. deletions, translocations etc but these are contributory rather than causative

Driver mutations confer growth upon the cell, carrying them and have been positively selected during the evolution of the cancer
Passanger mutations do nt confer growth advantage but happen to her present in an ancestor of the cancer cell when it acquired a driver mutation

Question 6

what is the difference between normal haemopoiesis and malignant haemopoiesis?

Answer 6

normal- can be polyclonal

Malignant- usually monoclonal

Question 7

types of haematological malignancy

-name the 3 ways in which they can be categorised?

Answer 7

-speed of presentation:
Acute or chronic

-Site:
Medullary (marrow)/extramedullary
Blood (leukaemia)/lymph-node (lymphoma)

Based on lineage:
Myeloid
Lymphoid

Question 8

describe the following malignancies:

• Acute Myeloid leukaemia (AML)
• Acute lymphoblastic Leukaemia (ALL)
• Chronic Myeloid Leukaemia
• Chronic Lymphocytic leukaemia
• Myeloma

Answer 8

• a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells
• overproduction and accumulation of cancerous, immature white blood cells, known as lymphoblasts.
• increased and unregulated growth of predominantly myeloid cells in the bone marrow and the accumulation of these cells in the blood (philadelphia chromosome)
• In CLL the abnormal cells develop from the lymphoid blood stem cells. The cancerous white blood cells are B cells, can involve blood, bone marrow and lymph nodes

also get high grade and low grade lymphoma i.e. malignancy in lymph nodes

Plasma cell malignancy in marrow

Question 9

Acute leukaemia

• give the definition (3)
• types?

Answer 9

-rapidly progressive clinical malignancy of the marrow/blood with maturation defects
excess of blasts >20% in blood or BM
dec/loss of normal haemopoietic reserve

-ALL, AML

Question 10

Acute lymphoblastic leukaemia

• disease of what cell?
• common in what age group?
• presentation? (3)

Answer 10

• lymphocytes
• childhood

-marrow failure = anaemia, infections, bleeding 
leukaemia effects, high WCC and involvement of extra-medullary areas e.g. CNS
lymph nodes might cause evens obstruction 
Bone pain (endostium expands)

Question 11

Acute Myeloid Leukemia

• common in what age group?
• cause?
• Presentation?
• subtypes characteristically present with what?

Answer 11

• elderly
• de novo mutation or secondary to chronic blood disorder
• similar to ALL

-DIC- disseminated intravascular coagulation
Gum infiltration

Question 12

Investigation in acute Leukemia

• what is seen on investigation?
• in what disease are Auer Rods seen?
• definitive Dx via what?

Treatment of acute leukaemia

• ALL?
• AML?
• SE of treatment (probs of marrow suppression (3) + general SE)
• what form of treatment in potentially curative in some patients?

Answer 12

-blood count and film
Coagulation screen
Bone marrow aspirate (Morphology, immunophenotyping, Cytogenetics, Trephine)

-Blood film:
reduction in normal + presence of abnormal
abnormal blasts cells with high nuclear:cytoplasmic ratio
Bone marrow:
morphology- mononuclear
immunophenotyping used to check if lymphoid or myeloid

• acute myeloid leukaemia
• immunophenotyping

-Multi agent chemo
can last 2-3 yrs
different phases of treatment of varying intensity (induction, consolidation, intensification maintenance)
targeted treatments at certain subsets

-Multi agent chemo
intensive
2-4 cycles of chemo
prolonged hospitalisation

Hickman lines used in both cases

-Anaemia
Neutropenia (severe, drawn out infection)
Thrombocytopenia (purpura & petechiae)
general:
Nausea and vomiting
Hair loss
Liver/renal dysfunction
tumour lysis syndrome
infection
late effects (loss of fertility, cardiomyopathy)

-Allogenic stem cell transplantation

Question 13

What kind of infections should be considered in a neutropenic patient?
-management of neutropenic fever?

Answer 13

-gram neg organisms, if prolonged and unresponsive to antibiotics then think fungal
also consider protozoal

-empirical treatment with broad spec antibiotics covering gram negs

Question 14

what subgroup of leukaemia is associated with a coagulopathy?

Answer 14

acute promyelocytic leukaemia

treated with vitamin and Arsenic