Acute Leukaemia Flashcards
define acute leukaemia
neoplastic proliferation of lymphoid precursors (myeloid or lymphoid)
rapid onset
immature (blast cells high nuclear cytoplasmic ratio, diffuse chromatin pattern and nuclei )
bone marrow failure (infilitration and replcament of normal cells)
anaemia: fatigue breathlessness pallor
neutropenia: recurrant infection
thrombocytopenia: bleeding epistaxis bruising
aml epidemiology
risk increases iwth age
worse prognosis
40% are adults
AML has abberation in chromsome/structure
translocation t(15;17)
breakpoint in chromsome 15 and 17 translocation , distal parts of chromsome join to wrong ends
seen in acute promyelocytic leukaemia
also t(8;21)
chromosonal duplication in AML
+8 and trisomy 21 AML and ALL predisposition, extra copies of proto-oncogenes
chromsomal loss or deletion in AML
hotspots : 5/5q and 7/7q
possible loss of tumour supressor genes
one copy may reduce haemopoiesis or dna repair
can be partial or total
genetic mutation in acute leukaemia
NPM1, CEBPA point mutation good prognosis
partial duplicaiton of FTL3 (BAD PROGNOSIS)
risk factors for aml
familial /constitutional predisposition
irradiation
anticancer drugs (may damage precursor cells)
cigarette smoking
Leukaemogensis type 1 and type 2 in AML
requires 2 hits to be pathogenic
type 1 promote proliferation and survival
type 2 block differentiation followed by apoptosis
core binding factor
transcription factor master of haematopoiesis binds corepressors
seen in t(8:21) and inv(16)
patient presents with haemorrhage cerebral or sudden onset of bruising/bleeding, which leukaemia?
acute promyelocytic leukaemia t(15;17), required early diagnosis
block is further down pathway abnormal promyelocytes
cogulation abnormality DIC and hyperactive fibrionolysis
hypergranular auer rods are present on blood film
variant form bilobed nuclei
AML OR ALL
cytological features: blast cells auer roads cytoplasmic granules joined together to make crystal
cytochemistry myeloperoxidase stains brown
sudan black B identifies myeloid
non specific esterase myeloid
Immunophenotyping: antigens on cell surface
flow cytometry, immunophenotyping. express Tdt (ALL) immature cell
AML : MPO
clinical features of AML
Bone marrow failure (anaemia neutropenia thromboycytopenia)
splenomegaly hepatomegaly
gum infiltration (if monocytic ) overgrowth of gums
lymphadenopathy
skin (superficial infection)
CNS (monocytic) cranial nerve palsy
may present with septic shock
pin point petechiae
DIC - can present with peripheral vascular obstruction
Hypervisocity if wbc very high retinal haemorrhage/exudates
diagnosis of AML
blood film
auer rods or granules
aleukaemic leukaemia -> do a bone marrow aspirate
immunophenotyping
cytogenetic studies all patients prognostic factor and to select treatment (apml direct treatment affect)
which aml has good prognosis
t(8:21) and inv(16) core binding
t15:17 apml
treatment of aml
supportive care, red cell platlet ffp if DIC
antibiotics , long line central port
allopurinol from dying cells uraemic acid
chemotherapy combination therapy at least 2 drugs, synergistic , non overlapping toxicity
treatment of apml
A drug called all-trans retinoic acid (ATRA)
promyeloycytes mature so are no longer leukaemia cells
arsenic trioxide has a similar effect
has good prognosis
ALL clinical features (how is it different to AML)
similar to AML bone marrow failure etc. however lymphadenopathy more common (thymic enlargment)
also bone pain in long bones more common
ALL genetic prognosis mutations
hyperdiploidy t12:21 t1:19 good
hypodiploidy t4;11 - poor
t9;22 philadelphia chromsome - improved with tyrosine kinase inhibitors ( bcr-abl1 fusion gene)
(feature of chronic myeloid leukaemia but also a feature of all in older/adults )
what is the importance of immunophenotyping in ALL?
aml vs all treated differently
t-lineage (15%) b lineage 85% ALL treated differently
other invesitgations : blood count/film bone marrow aspirate immunophenotyping (cytogenic always), blood grouping lft electrolytes
philidelphia +ve need imatinib
what additional therapy is needed for ALL vs AML?
systemic + CNS directed as it migrates into CSF
give drugs into CSF or those which cross BBB
treat longer for boys (+1yr) as testes is often affected
