leukaemia / lymphoma Flashcards
most common childhood cancer
ALL
most common type of ALL
B-ALL (85%)
T-ALL (15%)
peak age of ALL presentation
2-5y
4 syndromes a/w ALL
a. Down syndrome
b. NF1
c. Bloom syndrome
d. Ataxia telangiectasia
biggest prognostic factor for ALL
response to induction!!
ALL: favourable vs not favourable genetics
favourable:
1. Hyperdiploidy (>50)
2. Trisomies 4, 10
3. ETV-RUNX protein (t12;21)
not favourable:
1. Hypodiploidy (<44)
2. Philadelphia t(9;22)
achieving remission after end of induction measured by?
MRD - must be <0.01% by D29
ALL risk factors
i. Age > 10y or <1y
ii. WCC > 50 or CSF/testicular involvement at diagnosis
iii. Cytogenetic/molecular
iv. Response to induction – biggest prognostic factor
for FRACP, DIC + leukaemia = what kind?
APML
very specific FRACP features for AML
- Subcutaneous nodules – ‘blueberry muffin’ lesions
- Infiltration of gingiva
- DIC (APML**)
- Discrete masses – chloromas, granulocytic sarcomas
bone marrow findings of ALL vs AML
ALL 85% blasts, high nucleus:cytoplasm ratio
AML 20% blasts, with auer rods
describe the mutation in APML, and therefore its treatment
t15;17 = PML-RARA: responsive to all-trans-retinoic acid (ATRA, tretinoin)
survival rate of ALL vs AML
ALL: up to 99% with favourable genetics, say 90%
AML: 60-70%
down syndrome: AML or ALL?
ALL: 20x more common EXCEPT in first 3 years of life
- worse cytogenetics, worse prognosis
- T21 more sensitive to MTX
AML: better survival in T21!
why are FBEs important in T21 neonates?
10% get transient leukaemia/MPD (high leuks, blasts, low plt/Hb)
and 20-30% will develop leukaemia by 3y
bcr-abl: what’s the mutation and Rx
t(9;22) > imatinib TK inhibitor
JMML syndromic risk factors
- noonan’s
- NF1
most JMML have mutations in what pathway?
RAS/MAP kinase pathway
key features of JMML
- 1/3rd present with an URTI with hepatosplenomegaly and a rash
- *monocytosis *
most cases of infant leukaemia (<1y) from what mutation?
> 80% MLL gene (11q23 band translocation; majority t(14;11)) - and this is a shit one
HLH: most common age group
birth to 18m
pathogenesis of HLH
trigger > abnormal immune activation: macrophages eat up RBC and make cytokine storm, but NK and CD8 T cells can’t shut the macrophages down
most familial HLH is caused by what kind of problem?
defect in perforin, so NK/CD8 can’t do their job against the macrophages
aetiology of HLH
- genetic mutation
- infection - EBV**
- malignancy - esp lymphoid
- macrophage activation syndrome e.g. JIA/other rheum
symptoms of HLH
- fever ***
- rash - macpap or petechiae
- hepsplen
- lymphadenopathy
- resp distress
- CNS signs
… so very non-specific really
key Ix of HLH
- cytopaenia (Hb, plt, neuts)
- high ferritin
- high TG
- hepatitis
worst prognostic factor for HLH
higher ferritin
clinical presentation of lymphomas vs leukaemia
lymphomas less constitutional symptoms (H 1/3, NHL 10%). More often have regional lymphadenopathy
concerning areas for lympahdenopathy
non-cervical and supravlacivular
types of lymphoma
HL vs NHL (DLBCL, lymphoblastic lymphoma, burkitt’s, ALCL)
presence of B symptoms matters for which cancer
HL (NOT NHL)
classic biopsy finding of HL
Reed-Sternberg…but also seen in EBV!
HL vs NHL
HL: spread continguously, rarely extra-nodal. prognosis BETTER
NHL: non-contiguous spread, often extra-nodal e.g. skin, GI
epidemiology of HL - ages and sex
M:F 3 to 1
rare <5, peak 15-35y
lymphoma and SOB - what to think of?
mediastinal mass (bulky >1/3 of diameter) > obstruction / SVC compression, dangerous for GA
5-year OS for HD of all stages is…?
> 80%
favourable prognostic factors for HL
<10 yo, female, favourable subtypes (LP and NS) and Stage I non-bulky disease
poor prognostic factors with a HL relapse
<1y from completion of tx
B symptoms
extra-nodal
which is more common in children - HL or NHL
NHL 60%, esp Burkitt’s younger, DLBCL adolescents
BL vs DLBCL
BL - highly aggressive. germinal centre B cells. mainly abdo primary, (jaw for africans) with bone / CNS mets. “starry sky” appearance. TLS
DLBCL - aggressive. mature B cell. mainly mediastinal /abdo primary, RARELY with bone/CNS mets. TLS UNCOMMON
types of Burkitt’s
endemic = African, jaw, younger, upstream of c-myc, CNS > BMA, a/w EBV
sporadic = worldwide, abdo primary, a bit older (~11y), at c-myc, BMA > CNS, no EBV
survival rate of PTLD
20-35%
