Leukaemia 🩸🩸 Flashcards
Acute Myloid Leukeamia (AML)
Mostly in which age and gender?
Survival %?
Older population (64 years)
More in MEN
Life risk 0.5- 30% survival
Subtypes of Acute Myloid Leukeamia AML x4
Name and describe
- De Novo AML:
No risk factors - Secondary AML: progressed from another myeloid malignancy
- Therapy Associated AML: occurred following previous chemotherapy or extreme radiotherapy
- Familial AML: inheritable mutation that predisposes AML
Clinical presentation of Acute Myloid Leukeamia AML 3
- Infection, sepsis = decreases white blood cells
- Fatigue, Shortness of breath = decrease red blood
- Bruising, perechiae, bleeding = decreased platelets
AML
medication to treat
Azacitidine
Azicitidine
Moa
Side effects tolerable?
DNA methyltransferasw inhibitor
Reserves methylation induced silencing of tumour suppressor genes
Side effects are tolerable
Molecular target in AML
Midostaurin
MOA
SIDE EFFECTS
FLT3 inhibitor
FLT3 receptor is mutated in 30% of AML
Side effects: higher anaemia and rash
Acute Lymphoblastic Leukaemia ALL
More common in…?
Subtypes of ALL
Paediatrics, second incident peak in elderly
Separates into B cell and T cell subtypes
Acute Lymphoblastic Leukaemia ALL
Clinical presentation?
Same as AML, but may have
Enlarged lymph nodes, higher risk of CNS involvement
Acute Lymphoblastic Leukaemia ALL
Fit for chemotherapy:
- High dose chemo
- If CD20+ then ADD Rituximab
- If Philadelphia Chromosome +ve = add TKI
- ALLOGENIC STEM CELL TRANSPLANT for high risk patients
- aim to cure
Acute Myloid Leukaemia
Fit for intensive chemotherapy….
- High dose chemo - cytarabine + anthracycline
- Add midostaurin IF FLT3 MUTATION POSITIVE
- ALLOGENEIC STEM CELL TRANSPLANT IF HIGH RISK
*AIM TO CURE
Relapse Acute Lymphoid Leukaemia
Treatment? 2
- Blinatumomab = BITE therapy
- Chimeric Antigen Receptor T-cells (CAR-T)
Blinatumomab - BITE therapy
Bi-specific T-cell engager antibody construct (BITE)
Binds simultaneously CD3 cytotoxic t-cells to CD19 positive Leukaemia B cells.
Chimeric Abtigen Receptor T cell (CAR-T) process
Moa
Engineered receptors that direct the T cells against tumour cells.
Once re-infuses in the patient, the Tcells entrants, proliferate and kill the tumour cells and also promote surveillance.
Side effects of CAR-T cells and BITES
- Cytokine release syndrome (CRS) =
INFLAMMATORY STATE driven by cytokines released by CAR-T
ie
Fever, flu like symptoms,
Rapidly leading to hypotension, shock, cardiac arrest. - Neurotoxicity
How to manage the side effects of CART and BITES
- CYTOKINE RELEASE SYNDROME
= tocilizumab - Neurotoxicity
= dexamethasone
Chronic Myeloid Leukaemia:
Stat’s?
Age 50-60
Predicted to be most common Leukaemia by 2050
Most patients have normal life span
Chronic Myeloid Leukaemia:
Prognosis
Asymptomatic
May have large spleen = causes early satiety
Chronic Myeloid Leukaemia:
Diagnosis
1.FBC have overall increase in myeloid blood cells (neutrophils, basophils, eosinophils
- Genetic testing to show part of Chromosome 9 and 22 joined (translocated) = results in creation of BCR-QBL1 gene
What is the Philadelphia Chromosome?
Translocation of abl on chrom 9 to brc on chrom 22= formation of brc-abl fusion transcript.
The brc-abl transcript produces the oncogenic tyrosine kinase.
Chronic Myeloid Leukaemia:
Treatment
- Must treat with TYROSINE KINASE INHIBITORS
*Resistance to TKi may need allogenic stem cell transplant
Chronic Myeloid Leukaemia:
Treatment of chronic phase
First line NAMES
Imatinib
Dasatinib
Nilotinib
Is ponatinib first line for
Chronic Myeloid Leukaemia ?
No. It is a 3rd generation TKI =
Reserved for RESISTANT/REFRACTORY DISEASE.
What are the interactions with Dasatinib?
Avoid PPI, H2A
antacids need a 2 hour gap (so does nilotinib)
If patients reach deep remission (<0.01% bcr-abl) can they stop TKI?
Yes. If on them for long enough (3-8 years)
50% relapse
50% do not
Chronic lymphocytic Leukaemia (CLL)
Diagnosis
High lymphocyte count
Blood film- smudge cells
Chronic lymphocytic Leukaemia (CLL)
Treatment of
1. Asymptomatic
2. Symptomatic
3. Relapse, refractory
- Asymptomatic = no Treatment
- Symptomatic =
Older and unfit > venetoclax-obinutuzumab - Relapse = brutons kinase inhibitor > ibrutinib or acabrutinib
Chronic lymphocytic Leukaemia (CLL)
Relapse CLL trearment:
Ibrutinib
-MOA
-S,E
BRUTONS TYROSINE KINASE INHIBITOR Moa- CLL cells relies on BTK signal for survival and cell division
S/e:
Bleeding
Cardiac issues - AF, Hypertension,
Frequent infections
A major substrate for CYP3A4
Chronic lymphocytic Leukaemia (CLL)
Which drug is more selective than ibrutinib as a BTK inhibitor?
Acalabrutinib
Chronic lymphocytic Leukaemia (CLL)
Venetoclax -
Moa
S/e
bcl-2 (b-cell lymphoma) Inhibitor
S/e: tumour lysis syndrome
Take at same time every day with food
Major CYP3A4 substrate
Leukaemia summary
