Haematological Malignancies

Question 1

Basic Mechanisms of Leukaemia Development

Answer 1

Mutations in Bone Marrow:

• Viral - e.g. EBV
• Drugs
• Toxins
• Genetics
• Environment

Clonal Expansion

Transformed Cells Resistant to Apoptosis

Question 2

Consequences of Leukaemia

Answer 2

Increased WBC Count with potentially abnormal cells that increase susceptibility to infection

Bone Marrow Failure

• Anaemia
• Thrombocytopenia

Metastasis

Question 3

Acute Leukaemias

Answer 3

Usually short time course between discovery and death if untreated

Failure of maturation, useless cells accumulate in bone marrow then spill over into circulation

Question 4

Types of Acute Leukaemia

Answer 4

Myeloid or Lymphoblastic depending on cell line involved

Lymphoblastic - most common in children

• 85% cure rate in children
• 40% cure rate in adults

Myeloid - Most common in adults

Question 5

Chronic myeloid leukaemia

Answer 5

Replacement of normal bone marrow cells with cells of abnormal chromosome (90% have Philadelphia chromosome)

• Raised WBC count
• Splenomegaly

Middle age

Typically well in chronic phase but transformation to acute phase is associated with mortality

Question 6

Chronic lymphocytic leukaemia

Answer 6

Most common in older patients (peak age 72)

May be symptomless and diagnosed on blood test

Abnormal lymphocytes in lymphoid tissue (including bone);
Increased lymphocytes in blood

Enlarged lymph nodes

Infections more common

Question 7

Hodkin’s Lymphoma

Answer 7

Enlarged painless lymph nodes
Fever
Pruritus

Reed-Sternberg Cells

May invade other organs, e.g. lungs - present as pulmonary disease

Question 8

Non-Hodgkin’s Lymphoma

Answer 8

High or Low grade

Extranodal disease: GI, CNS, Endocrine, Skin, Pulmonary

Non-hodgkin’s Addociated with:

• Previous Chemotherapy
• Immunosuppressants
• EBV

Question 9

Chemotherapeutic treatment

Answer 9

Use of drugs to manage malignancies - Chemotherapy

DNA synthesis and mitosis is targeted - Cytotoxic drugs that kill rapidly dividing cells

Carried out in cycles with induction and maintenance phase

Question 10

Bone Marrow Transplantation

Answer 10

Transplant of stem cells to cure leukaemia

Question 11

Allogeneic Transplant

Answer 11

Cells which are genetically dissimilar and hence immunologically incompatible, although from individuals of the same species

Hence marrow transplant must be tissue matched

Question 12

Autologous Transplant

Answer 12

Must be cleared of abnormal cells via mAB

Question 13

How is bone marrow donation taken

Answer 13

Usually 750ml bone marrow removed from pelvis (don’t memorise value) under general anaesthetic
Or peripheral collection

Question 14

What does a bone marrow recipient go through

Answer 14

High dose chemotherapy and sometimes total body irradiation to destroy tumour cells & bone marrow

Question 15

Imatinib

Answer 15

Selective anticancer drug, very efective in chronic myeloid leukaemia

Question 16

Mechanism of Imatinib

Answer 16

Philadelphia chromosome produces bcr-abl protein which has tyrosine kinase activity that leads to cell proliferations - Imatinib inhibits TK Activity

Question 17

Rituximab

Answer 17

mAB against CD20 (lymphocyte antigen)

Used in non-hodkin’s lymphoma and chronic lymphocytic leukaemia

Question 18

Multiple Myeloma

Answer 18

Cancerous proliferation of plasma cells of bone marrow

Causes bone marrow failure

(same as myeloma)

Question 19

Clinical Presentation of Myeloma

Answer 19

Anaemia
High ESR
Back Pain
Unexpected Renal Failure
Unusual Fractures

Question 20

Treatments of Multiple Myeloma

Answer 20

Chemotherapy
Thalidomide
Bone marrow transplants in fitter patients