Lecture 11: Malignant blood disorders

Question 1

What are the four broad categories of blood and marrow cancers?

Answer 1

1) Leukaemias - Acute vs chronic (v different)
2) Myeloproliferative neoplasms (increased RBC)
- > Polycythemia vera
- > Essential thrombocytopenia
- > Myelofibrosis (Splenomeagly)
3) Lymphomas
- > Hodgkin lymphoma
- > Non-hodgkin lymphoma
4) Myeloma
- > Multiple myeloma etc

Question 2

What happens in leukemia?

Answer 2

White blood

• Proliferation of immature bone marrow cells (Myeloblasts and lymphoblasts)
• Expand and replace normal marrow cells
• Abnormal leukaemic cells spill over into blood (peripheral)

Question 3

What chromosome is involved in chronic leukaemia?

Answer 3

Philadelphia Chromosome

Question 4

How can acute leukemia be differentiated?

Answer 4

Acute myeloid leukaemia (AML)

Acute lymphoblastic Leukemia (ALL)

Question 5

What is the pathogenesis of leukaemia?

Answer 5

• Congenital / inherited risk factors
• Viral infections (Rare T-cell leukaemia)
• Radiation exposure
• Chemical/DNA damaging drugs

Question 6

Is it easy to identify the risk factors of leukemia?

Answer 6

Mostly cannot identify environmental or congenital risk factors

BUT… cytogenic and molecular changes found in 90% of acute leukemias

Provides info on:

• Pathogenesis (driver mutations)
• Prognostic significance
• Targets for therapy

Question 7

How does the Philadelphia chromosome play a role in leukaemia?

Answer 7

• Found in chronic and sometimes acute
• Fusion b/w 22&6 forming a gene (BCR-ABL) which forms a potent tyrosine kinase that drives proliferation of leukaemia cells

Question 8

What is the formed BCR-ABL gene in chromic leukemia used for?

Answer 8

It is target by imatinib therapy

Question 9

In which populations does ALL and AML occur in?

Answer 9

ALL - predominantly childhood

AML - predominantly adults

Question 10

What are the symptoms of acute leukaemia?

Answer 10

Signs and symptoms are presentation due to bone marrow failure

• Anaemia = Fatigue, dyspnoea, chest pain
• Neutropenia = Infection, wounds slow to heal
• Thrombocytopenia = Bruising and bleeding i.e patecheal bruising in lower limbs b/ gravity

Question 11

What are the other signs and symptoms of acute leukaemia in the organs?

Answer 11

Organ infiltration

Bone marrow = bone pain
Enlarged liver, spleen, lymph nodes
Gum issues

Question 12

What is seen on a full blood count in leukaemia?

Answer 12

• Low Hb / anaemia
• White cells increase (inc. circulating blasts, neutrophils low)
• Severe thrombocytopeania

Question 13

What is needed for diagnosis of leukeamia? what are some specialsied tests that can be done on it?

Answer 13

• Full blood count
• Bone marrow biopsy, aspirate, trephine

Specialised

• Immunophenotype (myeloid or lymphoid)
• Chromosomes
• Molecular studies

Question 14

What is seen on bone marrow biopsy in leukaemia?

Answer 14

• > 20% blasts myeloid or lymphoid

Question 15

Whats the therapy for acute leukemia?

Answer 15

General / supportive care

• Intensive transfusion support
• Red cells or platelets

Management of infection
- ID and lab support, antibiotic therapy

Vascular access
- Tunneled venous catheter

Patient and family support

Question 16

What is the chemotherapy for acute leukeamia?

Answer 16

Induction therapy: To induce remission

Consolidation: To eradicate residual leukemia cells

Maintainence therapy (Only in ALL) to keep patient in remission

Question 17

Write some notes on haemopoietic stem cell transplantation:

Answer 17

Autologous (must be in remission) or allogenic

Stem cells: Bone marrow, peripheral blood or cord blood

Question 18

What does the future hold for blood cancers?

Answer 18

Immunotherapy i.e CAR-T cells

Pts T cells isolated and engineered with CAR gene and expanded.

Then re-infused