Oncology / Haematology 1 Flashcards
A patient is started on Cyclophosphamide for vasculitis associated with Wegener’s granulomatosis. Which of the following is characteristically associated with Cyclophosphamide?
- Haemorrhagic cystitis
- Cardiomyopathy
- Ototoxicity
- Alopecia
- Weight gain
Haemorrhagic cystitis
What is the mechanism of action of cyclophosphamide?
Alkylating agent - causes cross-linking in DNA
List 3 adverse effects of Cyclophosphamide.
- Haemorrhagic cystitis
- Myelosuppression
- Transitional cell carcinoma
Name 2 cytotoxic antibiotics.
- Bleomycin
- Doxorubicin
What is the mechanism of Bleomycin (a cytotoxic antibiotic)?
Degrades pre-formed DNA
What is one adverse effect of Bleomycin?
Lung fibrosis
What is the mechanism of action of Doxorubicin?
Stabilizes DNA-topoisomerase II complex; inhibits DNA and RNA synthesis.
What is one adverse effect of Doxorubicin?
Cardiomyopathy
Name 4 Antimetabolites.
- Methotrexate
- Fluorouracil (5-FU)
- 6-Mercaptopurine
- Cytarabine
What is the mechanism of action of methotrexate?
What are 3 adverse effects associated with Methotrexate?
Inhibits dihydrofolate reductase and thymidylate synthesis
Adverse effects:
- Myelosuppression
- Liver fibrosis
- Lung fibrosis
What is the mechanism of action of Fluorouracil (5-FU)?
Adverse effects of 5-FU?
Pyrimidine analogues inducing cell cycle arrest and apoptosis by blocking thymidylate synthase (works during S phase).
Adverse effects:
- Myelosuppression
- Mucositis
- Dermatitis
What is the mechanism of action of 6-Mercaptopurine?
Adverse effects?
Purine analogue that is activated by HGPRTase, decreasing purine synthesis.
Adverse effects:
- Myelosuppression
What is the mechanism of action of Cytarabine?
Adverse effects of this drug?
Pyrimidine antagonist. Interferes with DNA synthesis specifically at the S-phase of the cell cycle and inhibits DNA polymerase.
Adverse effects:
- Myelosuppression
- Ataxia
List 3 drugs which act on microtubules.
- Vincristine
- Vinblastine
- Docetaxel
For Vincristine, describe:
i) The mechanism of action
ii) Adverse effects
i) Inhibits formation of microtubules
ii)
- Peripheral neuropathy (reversible)
- Paralytic ileum
For Vinblastine, describe:
i) the mechanism of action
ii) Adverse effects
i) Inhibits formation of microtubules
ii) Myelosuppression
For Docetaxel, describe:
i) The mechanism of action
ii) Adverse effects
i) Prevents microtubule depolymerisation and disassembly, decreasing free tubulin.
ii) Adverse effects: Neutropenia
Give an example of a topoisomerase inhibitor.
What is its mechanism of action?
Adverse effects?
- Irinotecan
- Inhibits topoisomerase I which prevents relaxation of supercoiled DNA
- Adverse effects: myelosuppression
For Cisplatin, describe:
i) Mechanism of action
ii) Adverse effects
i) Causes cross-linking in DNA
ii) Adverse effects:
- Ototoxicity
- Peripheral neuropathy
- Hypomagnesaemia
For Hydroxyurea (Hydroxycarbamide) describe:
i) Mechanism of action
ii) Adverse effects
i) Inhibits ribonucleotide reductase, decreasing DNA syntheis
ii) Adverse effects: Myelosupression.
Which of the following is most associated with thymomas?
- Myelodysplasia
- Thrombocytopenia
- Acute myeloid leukaemia
- Acute lymphoblastic leukaemia
- Red cell aplasia
Red cell aplasia
What is a thymoma?
The most common tumour of the anterior mediastinum.
Usually detected between the 6th and 7th decades of life.
Which diseases is a Thymoma associated with?
- Myaesthenia Gravis (30-40% of patients have a thymoma)
- Red cell aplasia
- Dermatomyositis
- also: SLE, SIADH
How does a thymoma cause death?
- Compression of airway
- Cardiac tamponade
Which of the following causes of Primary Immunodeficiency is due to a defect in B-cell function?
- Di George syndrome
- Chediak-Higashi syndrome
- Common variable immunodeficiency
- Chronic granulomatous disease
- Wiskott-Aldrich syndrome
Common variable immunodeficiency.
List 3 Primary Immunodeficiency disorders which are due to Neutrophil disorders.
- Chronic Granulomatous Disease
- Chediak-Higashi syndrome
- Leukocyte adhesion deficiency
What is the underlying defect in Chronic Granulomatous disease?
Lack of NADPH oxidase reduces the ability of phagocytes to produce reactive oxygen species.
Give a clinical overview of a patient with Chronic Granulomatous disease.
- Recurrent pneumonias and abscesses, particularly due to catalase-positive bacteria (eg. S. aureus) and fungi (e.g. Aspergillus).
- Negative Nitroblue-tetrazolium test
- Abnormal dihydrohodamine flow cytometry test
What is the underlying defect in Chediak-Higashi syndrome?
Microtubule polymerisation defect leads to a decrease in phagocytosis.
Give a clinical overview of a patient with Chediak-Higashi syndrome.
- Affected children have ‘partial albinism’ and peripheral neuropathy.
- Recurrent bacterial infections are seen
- Giant granules in neutrophils and platelets
What is the underlying defect in Leukocyte adhesion deficiency?
Defect of LFA-1 integrin (CD18) protein on Neutrophils.
Give a clinic overview of a patient with Leukocyte adhesion deficiency.
- Recurrent bacterial infections
- Delay in umbilical cord sloughing may be seen
- Absence of neutrophils/pus at sites of infection
List 3 B-cell disorders associated with Primary Immunodeficiency.
- Common variable immunodeficiency
- Bruton’s (X-linked) congenital agammaglobulinaemia
- Selective Immunoglobulin A Deficiency
For ‘Common Variable Immunodeficiency’, describe:
i) the underlying defect
ii) clinical presentation
i) Many varying causes
ii) Hypogammaglobulinaemia is seen. May predispose to autoimmune disorders and lymphoma
For ‘Bruton’s (X-linked) congenital agammaglobulinaemia, describe the underlying defect.
Defect in Bruton’s tyrosine kinase (BTK) gene that leads to a severe block in B cell development
Describe the clinical presentation of someone with Bruton’s congenital agammaglobulinaemia.
- X-linked recessive
- Recurrent bacterial infections are seen
- Absence of B-cells with reduced immunoglobulins of all classes.
What is the underlying defect associated with Selective Immunoglobulin A deficiency?
Maturation defect in B cells.
Describe the clinical presentation of someone with Selective Immunoglobulin A deficiency.
- The most common primary antibody deficiency.
- Recurrent sinus and respiratory infections
- Associated with Coeliac disease and may cause false negative coeliac antibody screen
- Severe reactions to blood transfusions may occur (anti-IgA antibodies -> anaphylaxis).
Which T-cell disorder is associated with Primary Immunodeficiency?
DiGeorge syndrome
What is the underlying defect in a patient with DiGeorge syndrome?
- 22q11.2 deletion
- Failure to develop 3rd and 4th pharyngeal pouches
List some common features of a patient with DiGeorge syndrome.
- Congenital heart disease (eg. tetralogy of Fallot)
- Learning difficulties
- Hypocalcaemia
- Recurrent viral/fungal diseases
- Cleft palate
List 4 combined B- and T-cell disorders.
- Severe combined immunodeficiency
- Ataxic telangiectasia
Wiskott-Aldrich syndrome - Hyper IgM syndromes
What is the underlying defect that causes Severe Combined Immunodeficiency?
- Many varying causes
- Most common (X-linked) due to defect in the common gamma chain, a protein used in the receptors for IL-2 and other interleukins.
- Other causes include Adenosine deaminase deficiency.
How might a patient with Severe Combined Immunodeficiency present?
- Recurrent infections due to viruses, bacteria and fungi
- Reduced T-cell receptor excision circles
- Stem cell transplantation may be successful
What is the underlying defect that causes Ataxic telangiectasia?
Defect in DNA repair enzymes
How is Ataxic telangiectasia inherited. List some features of the disease.
Autosomal recessive inheritance.
- Cerebellar ataxia
- Telangiectasia (spider angiomas)
- Recurrent chest infections
- 10% risk of developing malignancy, lymphoma or leukaemia
What is the underlying defect in a patient with Wiskott-Aldrich syndrome?
Defect in WASP gene
How is Wiskott-Aldrich syndrome inherited?
X-linked recessive.
List some features of Wiskott-Aldrich syndrome.
- Recurrent bacterial infections
- Eczema
- Thrombocytopenia
- Low IgM levels
- Increased risk of autoimmune disorders and malignancy.
Which defect is responsible for Hyper IgM syndromes?
Mutations in the CD40 gene.
List some presenting features of a patient with a Hyper IgM syndrome.
- Infection / pneumocystis
- Pneumonia
- Hepatitis
- Diarrhoea.
