Acute Leukaemia Flashcards
What are the 2 main acute leukaemia called
- Acute myeloid leukaemia
- Acute lymphoblastic leukaemia
What is haematopoesis
-the formation of blood cellular components
What is a multipotent stem cell
-unspecialised cell capable of 2 essential functions:
- generation
- differentiation
What is the hierarchy of cell differentiation
- stem cells - multipotent, source of all descendent cells and capacity for long/short term cell production
- progenitor cells - more limited spectrum of descendent cells, short-lived and highly proliferative
- precursor cells - committed to a single lineage with the ability to proliferate
- mature cells - terminally differentiated cells with specific functions
What is acute leukaemia
- aggressive disease associated with immature blast cells in the bone marrow/blood
- compromises the body’s ability to produce functioning blood cells
- has a severe presentation and aggressive course
What are the symptoms associated with acute leukaemia
symptoms associated with bone marrow failure:
- anaemia - fatigue, parlour
- Thrombocytopenia - bruising and bleeding
- Neutropenia - infection
others: bone pain, unexplained weight loss
Symptoms associated with organ infiltration:
- lymphatic system - lymphadenopathy
- CNS involvement - confusion, seizures
- Skin/gum- gum hypertrophy
- Mediastinal mass-T lineage AL4
How is acute leukaemia diagnosed
- full blood count and blood film
- bone marrow aspiration or biopsy
- U&E
- LFTs
- coagulation screening
- Imaging
What is the initial management of acute leukaemia
- rapid diagnosis & access to treatment required
- HLA typing - may require blood transfusion
- suppression of menses
- birth control and fertility consideration
- psychosocial support
- emergency treatment of complications may be required e.g hydration and correction of electrolyte imbalance, treatment of infection, prevention of uric acid neuropathy, correction of coagulation + blood product support
What is the treatment of acute leukaemia
Induction phase (4-6 weeks) -Intensive chemo to eradicate leukaemia clone and induce complete remission (CR)
Consolidation (4-12 weeks)/Intensification (8-12 weeks) phase
- further high dose chemo to eradicate residual undetectable leukaemia clone
- if patient not responding to treatment then would intensify chemo
Prolonged maintenance phase (2-3 years) (used in ALL not AML)
-lower dose outpatient treatment schedule to prevent relapse
What is CNS directed therapy and why and when is it done
The CNS is a sanctuary site for leukaemia therefore ‘preventative intrathecal chemotherapy’ is given to patients throughout all phases to prevent CNS relapse
What are supportive care therapy for acute leukaemia
pre-treat tumour lysis syndrome with:
- aggressive hydration
- allopurinol/rasburicase
prevention of febrile neutropenia with:
- IV antibiotics
- antifungals
- antiviral
- granulocyte-colony stimulating factor (GCSF) - more for ALL
prevention of chemotherapy induced emesis
pneumocystis jirovecii pneumonia (PCP) prophylaxis
What is tumour lysis syndrome and what can it lead to?
As cells die the cell content leak into the plasma
electrolyte imbalance:
- hayperkalaemia,
- hypercalcaemia,
- urate precipitation in urinary tract - renal dysfunction
What is acute lymphoblastic leukaemia (ALL)
the bone marrow makes too many immature lymphocytes
What are poor prognostic indicators of ALL
- unfavourable cytogenetics
- increased age
- male sex
- high WBC count at diagnosis
- presence of CNS disease
- poor response to initial treatment (e.g blasts present in bone marrow on day 14, completed response not achieved by day 28)
What is the side-effects of glucocorticoid and how can some of them be managed
- nightmares/psychaatric disturbances - so take earlier in the day
- GI ulceration - use PPI
- adrenal suppression
- hypergylcaemia
- glucoma
- immunosuppression
- osteoporosis
- dyslipidaemia
How does Asparaginase treatment work and what is asparagine and its importance
- Asparaginase catalyses the hydrolysis of asparagine to aspartic acid & ammonia
- this results in the depletion of asparagine in the blood
-Asparagine is an essential amino acid in lymphoid malignant cells required for protein synthesis
Lymphoid malignant cells cannot synthesis their own asparagine but normal cells can SO asparginase results in cytotoxicity of lymphoid malignant cells because protein synthesis is inhibited
What is PEG-asparginase
E.coli L-asparignase covalently linked to polyethylene glycol.
it has a low immunogenicity of the enzyme and prolonged half life - this increases the risk of an immune response
it is more effective than L-aspariganse at the same dose
What are the complication associated with Leukaemia
Acute complications:
- neutropenic sepsis
- thrombocytopenia
- anaemia
Long term complications:
- decreased fertility
- secondary malignancies
- end organ damage (e.g peripheral neuropathy, live, kidney and heart)
Managing co-morbidites:
- interacting medication
- renal impairment
- anti-coagulation
Psychological support:
-mental health co-morbidities
What is CAR T-cell therapy
it activates the patients own T cells to fight the cancer
however the cancer cells can be clever and disguise itself as normal cells by expressing really high levels of antigens or switching off T cell response
What is acute myeloid leukaemia (AML)
cancer of the blood and bone marrow
-caused by overproduction in immature monocytes and granulocytes
What are the prognostic factors for AML
- cytogenetics - 3 risk groups: good/intermediate/poor risk
- age and performance status - above 50yrs bad and complete remission fails progressively
- % blasts in marrow after 1st course of treatment: high levels linked to short remission and poor OS
- secondary AML - following chemotherapy or myelosuppression
What is the assessment of minimal residual disease (MDR)
- it is important in advanced cancer
- it is measured at day 28 of treatment and then escalated to high risk if no change in their condition
