Lecture 7 - Leukemia And Lymphoma - Bench To Bed Side Flashcards
1
Q
Cytotoxic chemotherapy
A
- works primarily through the inhibition of cell division
- other rapidly dividing cells are affected
2
Q
Targeted therapy
A
- interfere with specific molecules required for tumour development and growth
- molecules often mutated or overexpressed in tumours
3
Q
Two main types of targeted therapy
A
- monoclonal antibodies
- small molecule inhibitors
4
Q
Monoclonal antibodies
A
- fragment antigent binding of a monoclonal antibody
- highly specific targeting
5
Q
Anticancer effects through a number of mechanisms
A
- recruit host immune system to attack the target cell
- bind to ligands or receptors, interrupting essential cancer cell processes
- carry a lethal payload, such as a radioisotype or toxin, to target the cell
6
Q
B cell lymphoma
A
- account for about 85% of all NHL diagnosis
- indolent NHL: prolonged median survival but generally considered incurable. New treatments needed to prolong survival, ultimate goal is to provide cure
- aggressive NHL: characterised by rapid growth but with the potential for cure. Higher initial cre rates, less toxic therapies for old and frail patients
7
Q
Treatment of B cell lymphomas
A
- chemotherapy and radiation: toxic, lack specific antitumor targeted activity
- B cell lymphoma: highly express cell-surface proteins, key potential targets for treatment
8
Q
CD20
A
- B lymphocyte surface molecule
- has a role in the development and differentiation of B cells into plasma cells
- expressed on late pro-B cells through to memory cells
- not expressed on early pro-B cells or plasma cells
- regulates intracellylar calcium, cell cycle and apoptosis
- disease is associated with deficiency - common variable immunodeficiency
- enable optimal B cell immune response, specifically against T-independent antigens
9
Q
CD20 expression and target
A
- Expressed in B-cell lymphomas, hairy cell leukemia and B cell chronic lymphocytic leukemia
- ideal target for passive immunotherapy: not shed, modulated, or internalized significantly upon antibody bingding
10
Q
Rituximab
A
- chimeric (mouse and human) monoclonal antibody
- directed against the B-cell antigen CD20
- depletes B cells by several mechanisms: direct antibody-dependent cellular cytotoxicity, complement-mediated cell death, signalling apoptosis
11
Q
Rituximab is currently PBS-subsidised for treatment of
A
- indolent lymphoma as initial therapy in combination with standard chemotherapy regimens
- relapsed and refractory indolent lymphomas as single-agent therapy and as initial therapy in combination with chemotherapy
- single agent maintenance therapy in follicular lymphoma
- in patient with DLBCL, it is approved for use as intiial therapy with chemotherapy
- use with chemotherapy in previously treated and untreated patients with CLL
12
Q
Small molecule inhibitiors
A
- typically interrupt cellular processes
- interfere with the intracellular signalling of tyrosine kinases
- TK signallingL molecular cascade that can lead to cell growth, proliferation, migration and angiogenesis
- compared to monoclonal antibodies: usually administered orally rather than IV, cheaper, less specific targetting, required daily dosing because half life is only hours
13
Q
CML
A
- disease characterised by massive myeloid hyperplasia with accumulation of immature and mature myeloid cell sin blood and BM
- affects both sexes most commonly between age 40-60
- incidence increase by prior irraidation
- not increased in frequency in MZ twins
- 3 phases: chronic, accelerated, blast crisis
14
Q
Philadelphia chromosome
A
- translocation of chromosomal materal between chromosomes 9 and 22
- results in formation of BCR-ABL hybrid gene
- encodes a protein TK that gives the cell a message to divide
- seen on light microscopy preparations of dividing cells cases
- detected by molecular techniques in all cases of CML
15
Q
Findings of CML
A
- FBC: neutrophilia, immature cells mainly myelocytes circulating in the peripheral blood, increase in circulating basophils. Anemia
- bone marrow biopsy: hypercellularity, increase in myeloid series, cytogenetic analysis and molecular analysis to detect BCR-ABL
- FISH: joint fusion
