Acute Lymphoblastic Leukaemia Flashcards
What is acute lymphphoblastic leukaemia?
malignancy of B or T lymphoblasts characterized by uncontrolled proliferation of abnormal, immature lymphocytes and their progenitors (lymphoid progenitor and haematopoietic stem cell)
- leads to the replacement of bone marrow elements and other lymphoid organs
What is pantocytopenia?
occurs when a person has a decrease in all three blood cell types
- erythrocytes, leukocytes and platelets
occurs as a result of the bone marrow’s reduced ability to produce normal blood cells
Where are lymph nodes located?
neck (cervical lymph nodes)
groin (inguinal lymph nodes)
armpits (axillary lymph nodes)
abdomen
chest (medistinal)
What are the signs and symptoms of acute lymphoblastic leukaemia?
signs
- neutropenia (low neutrophils), anaemia (low erythrocytes) and thrombocytopenia (low platelets)
= due to bone marrow suppression/myelosuppression
symptoms
- fatigue, flu like symptoms, fever, dyspnoea, paleness
- bruising and bleeding, repeated infections, swollen glands
- weight loss, bone pain,
How can acute lymphoblastic leukaemia be diagnosed?
bone marrow aspirate (testing fluid sample)
lumbar puncture (testing cerebrospinal fluid)
What does acute lymphoblastic leukaemia treatment depend on?
age
presenting white blood cell count
cytogenetics (study of the structure and properties of chromosomes)
What are the steps in ALL treatment?
induction - 4 weeks = induce remission
consolidation - 4-8 weeks = eliminate residual cancer cells
interim maintenance I - 8 weeks = all steps below decrease relapse risk
delayed intensification - 8 weeks
+/- interim maintenance II - 8 weeks
maintenance - 1-2 years for girls and 3 years for boys (as cancer can hide in testes)
What is remission?
Remission means that the signs and symptoms of your cancer are reduced due to cancer treatment
Remission can be partial or complete.
- partial
= cancer is present but tumour is smaller/reduced levels of cancerous cells
- complete
= cancer is undetectable
What drugs are used in induction?
vincristine
PEG aspargase (asparaginase) intramuscular
intrathecal methotrexate
high dose dexamethasone (steroid)
What is the mechanism of action of vincristine?
binds to the microtubular proteins of the mitotic spindle, leading to crystallization of the microtubule and mitotic arrest or cell death
- stops microtubule polymerisation (anaphase)
What are the side effects of vincristine?
constipation
alopecia (hair loss)
neuropathy (damage to the peripheral nervous system)
What is the mechanism of action of PEG aspargase IM?
asparaginase enzyme hydrolyzes L- asparagine to ammonia and aspartic acid
- leads to the depletion of L-asparagine (essential amino acid)
- inhibit protein synthesis in tumor cells by depriving them of the amino acid asparagine
What are the side effects of PEG aspargase? Why is it PEGylated?
allergic reactions can occur due to PEGylation
require increased liver function tests due to toxicity
PEGylated - increased half life which is useful as intramuscular formulation is painful to administer
What is the intrathecal route?
injection into the spinal canal, or into the subarachnoid space so that it reaches the cerebrospinal fluid (CSF)
What are the side effects of steroids?
increased appetite
hyperglycaemia - requires counting carbs
mood and behaviour changes
insomnia
What drugs are used in consolidation?
cyclophosphamide
6 mercaptopurine (oral)
cytarabine
What is the mechanism of action cyclophosphamide?
is an alkylating agent
- phosphoramide metabolite forms cross-linkages within and between adjacent DNA strands at the guanine N-7 position
- these structural modifications are permanent and eventually lead to programmed cell death.
What is the most common side effect of cyclophosphamide? How can it be prevented?
haemorrhagic cystitis
- is inflammation and bleeding from the lining of the bladder
- caused by cleavage of cyclophosphamide into metabolite acrolein
- prevent it by hydrating patient pre, during and post treatment
- can take mesna (sodium 2-mercaptoethane sulfonate)
What is the mechanism of action of 6 mercaptopuruine? What can you not take it with?
- is an antimetabolite
= interferes with nucleic acid synthesis by inhibiting purine (A and G) synthesis and metabolism
it cannot be taken with dairy products
- dairy products contain xanthine oxidase which metabolise it and inactivate it
What is the mechanism of action of cytarabine? What are the side effects?
antimetabolite and antineoplastic agent
- inhibits DNA polymerase
- is converted to cytarabine-5´-triphosphate, which is the active metabolite incorporated into DNA during DNA synthesis. This results in a cell cycle arrest in the S phase.
cause fevers
- makes it difficult to differentiate between infections and drug side effects
What drugs are used for interim maintenance? What is the mechanism of action?
IV methotrexate
- antifolate antimetabolite
- inhibits dihydrofolate reductase (DHFR), an enzyme responsible for the conversion of dihydrofolate into tetrahydrofolate
- THF is needed for the synthesis of nucleotides required for DNA synthesis thus inhibition results in blockage of cell proliferation and growth.
What are the side effects of methotrexate? What drugs interfere with it?
mucositis
- inflammation of the mucosa that line the mouth and GIT
penicillins reduce methotrexate clearance
- increases risk of toxicity
What drugs are used during intensification? What is the mechanism of action?
doxorubicin
- intercalation into DNA and disruption of topoisomerase-II-mediated DNA repair
- = introduces DNA strand breakages and prevents repair leading to cell death
- generation of free radicals and their damage to cellular membranes, DNA and proteins
What are the side effects of doxorubicin? What monitoring is needed?
side effects
- cardio toxicity = arrhythmias, LV dysfunction or heart failure
- photosensitivity
- neutropenia
monitoring
- echocardiogram to look at left ventricular ejection fraction
