Blood cancers Flashcards
What is the normal blast concentration in the bone marrow?
5%
What presentation of blast is present in the bone marrow for leukaemia diagnosis to be made?
25%
What is the most common childhood cancer?
Leukaemia
- makes up of 20-33% of childhood cancer
- more males affected than females
What’s the distribution of the following?
- ALL
- AML
- CML
- Juvenile CML
ALL 80% - peak incidence at 4 years AML 20% - stable incidence through to 10 years then increases in incidence CML - 2% Juvenile CML - 2%
What syndromes causes increase risk of ALL?
Down syndrome
- ALL > AML in > 3yo
Ataxia-telangiectasia
- neurodegenerative autosomal recessive condition secondary to mutations in ATM gene
- impaired repair of DNA
- ataxia, raised AFP > 2y, low IgA / G / E, increased sensitive to x-ray
Wiskott-Aldrich
- X-linked recessive
- mutation in gene that makes the WAS protein which is characterized by eczema, thrombocytopenia, immune deficiency, and bloody diarrhoea
Hypogammaglobulinaemia
What is the risk of ALL if a sibling is affected?
ALL in sibling - 2 to 4x risk ALL in monozygotic twin - 20% in 1st 6 years of life - >10% next 6 months - almost 100% if <6m
What is acquired cause for ALL / AML?
Radiation
Chemotherapy agents (mostly secondary leak are myeloid)
- alkylating agents
- topoisomerase II assoc agents (i.e. etoposide)
What syndromes results in increased risk of AML?
Down syndrome (< 3yo, AML > ALL) Klinefelter syndrome NF1 BM failure - Kostmann syndrome - Diamond-blackfan syndrome Chromosomal fragility - Faconi anaemia (AR, absent thumb / radii, short stature, cafe-au-lait spots, macrocytosis precedes thrombocytopenia then bone marrow failure occurs - Bloom - Xeroderma Pigmentosum
What are the difference in morphological features between ALL / AML?
Often hard to tell
- ALL: less cytoplasm, no granules or auer rods
- AML: more cytoplasma, often granules and auer rods (Faggit cells)
What are markers seen on flow cytometry for
- Pre B ALL
- T cell
Pre B ALL
- CD 19, CD 10
T cell ALL
- CD 3, CD4, CD8
What are good or bad cytogenetics?
Hyperploidy
- more than 50 chromosomes in blasts
- extra 4, 10 and 17
- better prognosis
Hypoploidy
- Less than 45 chromosomes
- poor prognosis
t(12:21)
- needs PCR / FISH
- slower relapse rate
t(9, 22)
- BCR ABL / philadelphia
- highly oncogenic fusion protein which continuously signals cell growth
t(4, 11)
- seen in infantile ALL
t(1:19)
- poor prognosis
t(8:140
- myc oncogene seen in Burkitt’s and mature B cell
- good prognosis
How does standard vs high risk differs?
Standard risk
- WCC < 50
- Age 1-9
- Cure rate 90%
High risk
- WCC > 50
- Age < 1 year , > 10 years
Other prognostic factors
- response to treatment (i.e MRD at end of induction were flow cyto detects 1 in 10000 blasts!)
- CNS / testicular (poor)
What are the blocks of ALL treatment?
Induction - dexamethasone - weekly vincristine - D4 Peg asparaginase - IT MTx \+/- daunorubincin if high risk
Consolidation (6weeks)
- Cyclophosphamide
- Ara-C
- Vincristine
- IT MTx continues
Intensification
- Hi dose MTx
Maintenance
- oral 6MP / MTx
- Monthly 5-day pulse dexamethasone
- Monthly vincristine
- IT Mtx
What vaccinations are contra-indicated during chemotherapy?
All live vaccines
- MMR, varicella, oral polio
Can have flu vaccination when neutrophils > 1
What are presentation features of penumocystic carinii pneumonia?
Rapid respiratory rate with no chest signs
CXR quickly progresses to white out
Diagnosed bbq BAL
Prophylaxis with cotrimoxazole unless having high dose MTx
- MTx / cotrimoxazole both reduce folate metabolism increasing potential for myelosuppression
- both drugs can also cause renal impairment and MTx renal clearance gets reduced
- cotrimoxazole displaces Mtx from being bound to protein –> increase concn in serum –> increased toxicity
