Cancer Flashcards
What is the pathogenesis of leukaemia?
Mutation of early haematopoietic progenitors, leading to excessive production of progenitors which replace normal bone marrow tissue. Loss of function erythrocytes, thrombocytes and leukocytes.
How can leukaemia be classified?
Acute or Chronic
Myeloid or Lymphoblastic
What is acute myeloid leukaemia?
Clonal proliferation of precursor cells which give rise to myeloid cells
What are the symptoms of acute myeloid leukaemia?
Pancytopaenia
- thrombocytopaenia: easy bruising
- neutropaenia: recurrent infection, slow wound healing
- anaemia: fatigue
How is acute myeloid leukaemia diagnosed?
Anaemia that is normocytic and normochromic
Very low platelet count
Low leukocyte count
What is the principle of leukaemia treatment?
- Chemotherapy to induce remission
- Consolidation to destroy remaining leukaemia
- Maintenance to remain in remission
When is haematopoietic stem cell transplant considered?
- Younger patients
- When there is a suitable donor
- First or second remission
What is acute lymphoblastic leukaemia?
Clonal proliferation of stem cells of the lymphoid lineage
What are the symptoms of acute lymphoid leukaemia?
Splenomegaly
Hepatomegaly
*Due to excessive B and T lymphocyte progenitor formation
What is the difference between acute and chronic leukaemia?
Acute is more aggressive; chronic develops more slowly
Acute prevents blood stem cells from maturing, chronic prevents the development of mature/maturing blood cells
What is chronic myeloid leukaemia?
Myeloproliferative neoplasm categorised by the abnormal proliferation of mature/maturing granulocytes
What are the symptoms of chronic myeloid leukaemia?
Slow onset –> some patients are asymptomatic
Splenomegaly
Elevated WBC and platelets
What is the Philadelphia gene?
BCR region from chromosome 22 and ABL region from chromosome 9 undergo a fusion reaction to form the Philadelphia gene. This results in a tyrosine kinase signalling protein that is always “on”, resulting in uncontrolled cell divison.
What is the treatment of Chronic Myeloid Leukaemia?
Tyrosine Kinase Inhibitor: Imatinib
Imatinib MOA?
Competitively inhibits BCR-ABL tyrosine kinase by blocking the ATP binding site, preventing the conformation switch to the active form. this blocks the proliferation and induces apoptosis of BCR-ABL positive cell lines.
Imatinib ADR?
ADR usually arise during a few months of treatment. Neutropaenia, thrombocytopaenia Gastrointestinal bleed Nausea, vomiting --> take with food Diarrhoea --> loperamide Maculopapular rash
What should be monitored prior to initiating imatinib?
Full blood count Serum creatinine Urea, electrolytes Liver function test TSH INR
How often should patients taking imatinib be monitored?
Weekly for the first month
Biweekly for the second month
Every 2-3 weeks thereafter
What drugs interact with imatinib?
Imatinib is a CYP3A4, 2C9, 2D6 and 2C19 inhibitor, thus reacts with any drugs that are inducers or inhibitors of these enzymes.
Carbamezapine: CYP3A4 inducer
Azole antifungal: CYP3A4 inhibitor
Warfarin: metabolised by CYP2C9 and 3A4
What is lymphoma?
Chronic malignancy of mature lymphocytes
What is Hodgkin lymphoma?
Malignancy wherein Hodgkin Reed-Sternberg cells (a type of B cell) are mixed in with non-neoplastic cells
What is the difference between Hodgkin and Non-Hodgkin lymphoma?
Hodgkin Lymphoma is diagnosed by the presence of Reed-Sternberg cells. Hodgkin lymphoma also typically begins in the upper body, Non-Hodgkin lymphoma begins anywhere/
What are the symptoms of Hodgkin’s lymphoma?
Asymptomatic lymphadenopathy B symptoms - fever - night sweats - unintentional weight loss
How is Hodgkin’s Lymphoma staged?
Stage 1: single node
Stage 2: two nodes on one side of the diaphragm
Stage 3: bilateral nodes
Stage 4: extranodal (i.e. nodes on other parts of the body)
What are the treatment options for Hodgkin Lymphoma?
Multi agent chemotherapy
- ABVD
- BEACOPP
Radiation therapy
What is the best treatment option for early-stage Hodgkin lymphoma?
ABVD: doxorubicin, bleomycin, vincristine, darcapazine
What is the best treatment for late-stage Hodgkin lymphoma?
BEACOPP: bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone
When is radiation therapy considered in Hodgkin’s lymphoma?
Poor prognosis
Risk of relapse
What is Non-hodgkin lymphoma?
Haematological malignancy arising from lymphocytes (B, T, NK)
What are the subtypes of non-hodgkin lymphoma?
Aggressive/highly aggressie
Indolent
What are the symptoms associated with aggressive NHL?
Fever, night sweats
Weight loss
Rapidly growing mass
What are the symptoms associated with indolent NHL?
Waxing/waning lymphadenopathy
Hepatomegaly
Splenomegaly
Cytopaenia (loss of functional blood cells)
What is the treatment of NHL?
R-CHOP:
- rituximab
- cyclophosphamide
- doxorubicin
- vincristine
- prednisone
Why is chemotherapy administered in cycles?
Chemotherapy only attacks cells that are currently dividing. By the time cancer is detected, those cells have stopped dividing and are in the G0 phase. Thus, chemotherapy is administered in a cycles to target cancer when it is dividing. Intermittent cycles also allow normal tissues time to recover.
Rituximab MOA
rituximab is a monoclonal antibody that binds to transmembrane antigen CD20 to initiate cell lysis. This is done via 4 mechanisms:
- Antigen-dependent cell cytotoxicity
- Antigen-dependent cell phagocytosis
- Complement-dependent cytotoxicity
- Apoptosis
How are chemotherapy doses calculated?
Body surface area:
root of height*weight over 3600
What premedications are given for rituximab?
Loratadine and paracetamol to prevent hypersensitivity, for pain relief and to reduce infusion-related reactions.
What happens if patients have rituximab-induced infusion reactions?
Treat symptoms of infusion reaction then administer at a reduced infusion rate.
Rituximab ADR?
Serious infection
Infusion-related hypersensitivity reactions
CV AEs: exacerbation of angina, arrythmia, heart failure
Cyclophosphamide MOA?
Alkylating agent, adds alkyl group to nucleic acids, proteins and amino acids, preventing strand separation by cross-linking DNA.
Cyclophosphamide ADR?
Haemorrhagic cystitis (bleeding from bladder) Treat with fluids (unless fluid restricted) and MESNA.
Doxorubucin MOA?
Anthracycline antibiotic, causes cell fragmentation by inhibiting DNA and RNA synthesis
Doxorubicin ADR?
Cardiotoxicity
Hand-foot syndrome
Dehydration
Vincristine MOA?
Vinca alkaloid, inhibits production of spindle fibres therefore inhibits mitosis in cancer cells.
Vincristine ADR?
Constipation due to autonomic neuropathy
Treat with prophylactic laxatives
Vincristine must be administered…
…via IV
Prednisone MOA?
Glucocorticoid, reduces the number of circulating lymphocytes, eosinophils and monocytes and decreases inflammation.
