CP7-3 Acute leukaemia and MDS Flashcards
What cause leukaemia?
Accumulation of early myeloid or lymphoid precursors in the bone marrow, blood or other tissues potentially due to somatic mutation in a single cell within a population of early progenitor cells
What can cause secondary acute leukaemia?
Chemotherapy/radiotherapy for previous malignancy
Other haematological conditions
What is the median age of presentation of patients with acute myeloid leukaemia (AML)?
69
After what age does survival rate of AML become poor?
After 60
What is the trend if AML incidence?
It is increasing
Why is survival rate of AML poorer in older people?
Older people tend to have mutations and abnormalities
What are 3 clinical features of patients with AML?
Anaemia
Increased risk of infection
Easy bruising and haemorrhage as less platelets in blood as not as much being made in bone marrow and proliferation of tumour cells takes up the space/takes over
What organs may become infiltrated with leukaemia cells in AML?
Spleen
Liver
Meninges
Testes
Skin
Gum
What is an example of an acute myeloid leukaemia?
Acute monocytic leukaemia
What are some haematological features might patients with AML present with?
Anaemia
Low of high WCC with circulating leukaemia
Low platelets
How is AML diagnosed by looking at a patients blood?
Morphology of blood cells
Immunological markers
Cytogenetics
What are some known cytogenetic markers for leukaemia?
T(8;21)
Inv(16)
T(15:17)
What factors are important when determining prognosis in AML?
Patients age
Chromosomes and cytology of mutated cells
Molecular features
Extramedullary disease
Disease doesn’t respond to treatment
What are two molecular features that are looked for when determine prognosis in AML?
NPM1
FLT3-ITD - gives a bad prognosis if this is present
How is AML usually treated?
With intensive chemotherapy involving 3-4 cycles of intravenous cytotoxic drugs given centrally
Bone marrow transplant in high risk patients
What are risks of intensive chemotherpay?
Death
Sepsis
Alopecia
Infertility
Tumour lysis
What percentage of patients with AML go into complete remission within cycle 1?
Around 80-85%
What new treatments for AML are being used?
Targeted treatments for specific abnormalities expressed on leukaemia cells
Individualised treatment
Either can be used +/- chemotherapy
What percentage of patients have FLT3 mutation?
Approx 30%
Why does FLT3 lead to a poor prognosis?
As they cause constitutive activation of FLT3 receptors
What are some examples of FLT3 inhibitors that are being developed?
Midostaurin
Quizartinab
Crenolanib
Gantesebib
Gliteritinib
Which patients receive immediate intensive therapy for AML?
if critically ill with rapidly progressive disease that is causing respiratory / neurological / other organ compromise.
What causes poor survival in AML?
high proportion of patients have unfavourable cytogenetics
frequent involvement of more immature leukaemic precursor clones
multidrug resistance
antecedent haem disorder
higher levels of co-morbidity due to epidemiology
When will patients with AML usually relapse for the first time?
Within 18 months of intensive chemotherapy
How long do patients need to be cancer free with AML to be classed as likely cured?
4 years post chemo
What options for treatment are there for relapse of AML?
Further intensive chemo if possible
Otherwise non intensive treatment/experimental options
What are some non intensive treatments for AML?
Low dose chemotherapy with cytarabine
Treatment with hypomethylating agents
Who is cytarabine not commonly used for?
patients with adverse cytogenetics
What are two hypomethylating agents used in non-intensive treatment of AML?
Decitibine
Azacytidine
What treatment for AML was used in COVID?
Venetoclax
What is neutropenic sepsis?
Life threatening complication of chemotherapy
What are symptoms of neutropenic sepsis?
Fever
Hypotension
Organ impairment
How is neutropenic sepsis treated?
Broad spectrum IV antibiotics
what clinical symptoms do patients with ALL present with?
Fatigue
Bruising/bleeding
Weight loss
Night sweats
Hepatosplenomegaly
Lymphadenopathy
Mediastinal mass
What are the 4 general principles of ALL treatment?
1 - induction - 8 weeks
2 - intensification/CNS prophylaxis - 4 weeks
3 - consolidation - 20 weeks
4 - maintenance- 2 years
How are high risk patients with ALL treated?
With bone marrow transplant
When does relapse of ALL tend to occur?
Within 18 months of stopping maintenance chemotherapy
How is relapsed ALL disease treated?
With further intensive chemotherapy
Blinatumomab
Inotuzumab
CAR-T cells
BMT
Roughly how much does blinatumomab treatment cost just for the drug alone for one patient?
£135,000
How can monoclonal antibodies be used to treat ALL?
Monoclonal antibodies/cell antigen binding fragment and a toxin moiety which induces cell death targets CD22 of leukaemia cells for target treatment.
What is an example of a monoclonal antibody drug used in ALL treatment?
Inotuzumab
What does MDS stand for?
Myelodysplasia
What is MDS?
A heterogenous group of coronal bone marrow stem cell disorders that result in ineffective haematopoiesis with reduced production of one or more peripheral blood cell lineages
What are features of MDS?
Dysplasia
Inefficient haematopoiesis
Cytopenias
Increased risk of transformation to AML
What scoring system is used for MDS?
IPSS-R parameters
What prognostic variables in MDS are looked at in determining IPSS-R parameters?
Cytogenetics
BM blast %
Haemoglobin
Platelets
ANC
How are patients with low risk MDS managed?
Monitor patients and aim to improve QoL
Treat any symptoms e.g. erythropoietin for anaemia
Blood product support if necessary
How are patients with high risk MDS managed?
With intensive chemotherapy if possible
With bone marrow transplant if fit enough
If not fit or patient has complex cytogenetics consider treating with azacytidine
What are common complications of MDS?
Fatigue
Infection
Bleeding
Transformation to AML
