Malignancy Flashcards
What is the myeloperoxidase stain for on BM asp?
Shows up granulocytes and myelocytes yellow bits
Should be neg in ALL
What the esterase stain useful for on BMA?
Shows up monocytes red
Should be neg in ALL
?definition of acute leuk on BMA
> 20%blasts
😇Normal is less than 5%
?BMA FEATURES in ALL
Lymphoblasts, prob wall to wall
Monomorphic appearance
Blasts are usually small to med size, are larger than rcc, no cytoplasm
Cytoplasm they do have is blue-ish because agranular basophilic (high nuclear to cytoplasmic ratio, no granules
Chromatin “open” and is paler and less clumpy
May See vacuoles and nucleoli
Precursor Lymphoblasts will often have markers is has no place expressing (myeloid markers) - reflective of mutations
? What triggers ALL
Don’t really know - 2 crucial events
🍼Maturation arrest (stuck at blast phase)
👮🏾Loss of CONTROL of prolif
Some cytogenetic/molec predisp on Guthrie
More common in DS
?risk of ALL & AML in DS
DS 9-13% cases of AML
CURE rate higher with CHEMO alone (GATA-1)
10-30 x increased risk
10%will have a transient myeloproliferative disorder in newborn/early infancy
- high wcc and hepatosplenomegaly
- 70% spont remission, 30% progress to acute
Megakaryoblastic leuk at 1-3y
?subtypes ALL
Precursor B cell
T-cell (higher risk than pre-B ALL)
Mature B cell (Burkitts)
Directs therapy
What mutation is associated with TMD and AMKL in DS?
Mutations in GATA1 gene (5-10% of DS infants)
- found in BOTH TMD and AMKL
GATA 1 is a transcription factor crucial in erythro and megakaryopoiesis
30%TMD acquires other genetic abberations
?child cancer rate in NZ in
150 in 10 000 children per year 43%haem malig 💉💉💉Most leukaemia 34% (51 per 100 000) - peak of leuk in preschoolers (1-4y)👦🏼 9%lymphoma (13 per 10 000/y) 21%CNS tumours 💭
?prognostic features in ALL
Tumour biology very NB, cure rate overall now 90%
Cytogenetics:
👼>50 good, Trisomy 4,10 good hyperdiploid)
See photo!
Pres wcc is not diagnostic in T-ALL (new)
But in prec B-cell high risk is pres wcc >50
How to assess chemo sensitivity in haem malig?
Minimal residual disease >0.01%
Not detected under 🔬
?cure rates in ALL (3-5y)
90%overall
95% for standard risk
99% for double/triple trisomies or ETV6-RUNX1
Treatment targeted to BCR-Abl1 gene (t(9;22)
Imatinib/dasatinib
Tyrosine kinase inhibition, combination therapy has negated need for transplant
ALL Ph positive Current 7 year relapse free survival >70%
Classic CML with Philadelphia chrom
Infant ALL ? Common cytogenetic feature
Prognosis
Different kettle of fish, rare, most are MLL rearrangements and often have high presentation wcc
Much poorer outcomes, best case scenario 50/50 cure rate
?differences between ALL and AML chemo
ALL 3years fairly light chemo
AML 6months heavy duty and cytarabine based
AML ?cure rate
Second most common leu in childhood (less than ALL) 80-90% remission 50-60% disease free survival Inc incr with age 5y 60-65% OS
Key AML pres features
CNS 10%
BM and immune phenotype different to ALL: CD 13, 33
Masses or skin lesion (chloroma) extra medullary haematopoeisis
Gum hypertrophy
Others vague - wt loss, bruising, pancytopenia, bleeding.
NEED TO WATCH OUT FOR DIC
-thrombocytopenia
red cell fragments ALWAYS BAD (HUS, TTP, mech heart valve)
DS has x20 higher risk of leukaemia
AML ?features on blood film
Auer rods (always in the exam!)
Blasts larger with granules in cytoplasm
Chromatin is pale and more open, still have vacuoli
Classification AML
FAB 0-7 based on morph and histochem characteristics
WHO gives prognosis - based on morph, immunophenotype, and cytogenetic features
Acute promyelocytic leu
Bundles of Auer rods
May present with DIC, FAB M 3 does pred prog
Induction chemo with ATRA (unique, good prof if doesn’t die during induction, can get away without cytotoxic)
Reed Sternberg cells
Owls eye = hodgkins
Pathognomic and malignant
Often chronic course, may filter through surgical depts first, may get false FNAs (need and excision biopsy to capture)
Commoner in 2nd decade, more in females except when
Features HOdgkin
May be prolonged hx May be med mass Lymphadenopathy progressive Paraneoplastic phenom may be present (B sx, wt loss >10% over 6m, fever, drenching night sweats) Ann arbour staging
Mx of HL
PET may upstage or downstage disease or may allow avoidance further Radiotherapy
ALL signs and symptoms
Leukaemic infiltrate in bone marrow, pancytopaenia Anaemia, fever, bruising HSM, adenopathy Malaise, anorexia Peak incidence 2-5y preschool peak
ALL induction (to induce remission)
Around 28-30 days 1) pred as single agent first week 2) vincristine, Daunorubicin, asparaginase Intrathecal MTX 98% remission rate after!
Who requires radiation in ALL?
CNS INV
inadequate Rx response
T CELL ALL, high WCC
ALL Total duration Consolidation CNS reinduction Maintenance
24 months total
Maint part is 18m
ANZCHOG study 9 from Dec 2011
Nearly 90% cure
Indications for HSCT in ALL
Offered to persistently high MRD at end of induction Poor CYTOGENETICS Poor therapy response: Poor pred response failure to ach CR1 High flow day 15 High MRD
AML important clinical factors
What 2 parameters are predictive of outcome?
Infants now doing well 60-70%DFS if FAB M4/5 t(9;11) translocation Prognosis worse as age increases (>10y) CNS pos at dx not adverse 1) response to initial therapy 2) CYTOGENETICS Fav: t(8;21), t(5;17), inv 16 Fab 3
Adverse: (survival 17% at 8y) monopsony 5/7 Del long arm chrom 5 Abnorm long arm chrom 3 Complex karyotype >4abnorms
Role of HSCT in AML
AML CR2 and beyond
Refractory
High risk patients CR1
-should have MSD or alt donor transpl
Intermediate risk patients who had HSCT DFS 50% vs 39% so should have MSD if available
Low risk patients no transplant in CR1 (inv 16, t(8,21), trisomy 21
What is the Immunophenotype of APL (acute promyelocytic leukaemia)
t(15;17) M3
ATRA induces differentiation
FAVOURABLE PROGNOSIS
