Acute leukaemias Flashcards
AML & ALL
what is the dominant clinical feature of acute leukaemia?
bone marrow failure caused by accumulation of blast cells
what are the 3 main clinical features associated with bone marrow failure in acute leukaemia?
- anaemia
- neutropenia which can lead to infections
- thrombocytopenia which can lead to bleeding
acute leukaemia is normally defined as the presence of at least _____ of blast cells in the bone marrow or blood at clinical presentation.
20%
note: it can be diagnosed with less than 20% blasts if certain leukaemia-specific cytogenetic or molecular genetic abnormalities are present
a typical myeloid immunophenotype is ?
CD13+, CD33+, CD117, TdT-
Tdt expression defines what kind of lineage?
a lymphoid lineage
what are the most common driver mutations promoting clonal expansion in AML?
FLT3, NPM1, DNMT3A
what is the immunophenotype found in T-ALL?
CD2, cCD3, CD7
what is the immunophenotype found in B-ALL?
CD10, CD19, cCD22
Some AML cases are characterized by a gene-fusion event, which usually arises from translocations, with the most common being ?
PML-RARA, CBFB-MYH11 and RUNX1-RUNX1T1
AML is the most common form of acute leukaemia in adults and becomes increasingly common with age, with a median onset of 65 years. T or F.
True
what are the 6 main groups of AML recognised?
what is the characteristic features of the promyelocytic variation of AML?
bleeding tendency caused by thrombocytopenia and disseminated intravascular coagulation (DIC)
what are the characteristic features of the myelomonocytic and monocytic subtypes of AML?
gum hypertrophy and infiltration, skin involvement (leukaemia cutis) and CNS disease
what are the lab findings/investigations seen in AML?
- normochromic, normocytic anaemia
- thrombocytopenia
- neutropenia
- total white cell count is increased
- blood films shows blast cells + Auer rods
- bone marrow is hypercellular with many leukaemic blasts
Acute promyelocytic leukaemia contains which translocation?
t(15;17) on the PML and RARA gene which makes the PML-RARA fusion gene
Point mutations in which genes are frequent in AML?
What is the general supportive therapy for bone marrow failure (for AML & ALL)?
What is the aim of treatment for acute leukaemia?
what is the specific therapy for AML?
Maintenance therapy is of no proven value except in promyelocytic AML with all-trans retinoic acid (ATRA). T or F.
True
Midostaurin inhibits FLT3. T or F.
True
note: FLT3 mutations are bad :(
which translocations in AML are the most favourable ones?
t(8,21) and inv(16)
how is APML treated?
it is treated as for DIC with multiple platelet transfusions and replacement of clotting factors with cryoprecipitate or fresh frozen plasma.
also ATRA therapy is given n is combined initially with either arsenic trioxide or anthracycline
what is differentiation syndrome and its clinical features?
- aka ATRA syndrome may arise after ATRA treatment
- clinical problems (cuz of neutrophilia that follows differentiation of promyelocytes) include fever, hypoxia with pulmonary infiltrates and fluid overload
note: treat with steroids
what is complete remission defined as?
less than 5% blasts in the bone marrow, normal or near-normal peripheral blood count and no other signs or symptoms of the disease
what is the incidence of ALL is highest at which age?
3-7 years
B-cell lineage rep- resents 85% of cases and these have an equal sex incidence. T or F.
True
There is a female predominance for the 15% of T-cell ALL. T or F.
False
- male predominance
Within B-ALL there are several specific genetic subtypes such as what?
- t(9;22) [BCR-ABL1]
- t(12;21) [ETV6-RUNX1]
- rearrangements of the KMT2A (MLL) gene
About half of the pts with the Ph-like ALL have what kinda mutations?
CRLF2 over expression and JAK-STAT pathway mutations
IKZF1 deletions are also common
which signalling pathway is activated in most T-ALL cases?
NOTCH signalling pathway
Early T-precursor (ETP) ALL leukaemia expresses which markers?
Blasts in ETP ALL express T-cell marker CD7, but not CD1a and CD8 (these ones are for more mature cells)
what are the clinical features of ALL?
- bone marrow failure (ANT)
- organ infiltration- which can cause tender bones, lymphadenopathy, moderate splenomegaly, hepatomegaly and meningeal syndrome (headaches, diplopia etc.); fundal exam may reveal papilloedema and haemorrhage; fever; testicular swelling or signs of mediastinal compression (T-ALL)
what are the lab findings seen/investigations done in ALL?
- normochromic, normocytic anaemia
- thrombocytopenia in most cases
- white cell count may be decreased, normal or increased
- bone marrow is hypercellular with >20% leukaemic blasts
- biochemical tests may reveal a raised serum uric acid, serum LDH or hypercalcaemia(less common)
- radiography may reveal lytic bone lesions and a mediastinal mass(characteristic of T-ALL)
The risk of tumour lysis syndrome is highest in?
children with a high white cell count, T-cell disease or con- current renal impairment at presentation
what is minimal residual disease?
when small numbers of neoplastic cells/ leukaemic cells are detected by flow cytometry or molecular analysis even when the blood and marrow appear to be clear
what are the drugs used in the remission induction in ALL?
- Vincristine
- L-Asparaginase
- Corticosteroid (dexamethasone or prednisolone)
Vaneil likes Camryn
what are the drugs used in the consolidation period (to reduce tumour burden to very low levels) for ALL?
- Vincristine
- Cyclophosphamide
- Cytosine arabinoside
- Daunorubicin
- 6-Mercaptopurine
what drugs are used in CNS prophylaxis (to prevent involvement)?
- Intrathecal Methotrexate
- Cytosine arabinoside
- Corticosteroid
what drugs are used in maintenance therapy in ALL?
- 6-Mercaptopurine
- Methotrexate
- Vincristine
- Corticosteroid
how is BCR-ABL1 positive t(9;22) ALL treated?
with the use of TKIs like imatinib
how is ALL treated in relapsed patients?
Chimeric antigen receptor (CAR)-T cell therapy (the patient’s own T cells are programmed to kill B cells expressing CD19) usually followed by allogeneic SCT
which features of ALL carry a good prognosis?
- Hyperdiploidy (>50 chromosomes)
- the t(12;21) ETV6-RUNX1 translocation
the presence of MRD in adults after how many months of treatment is an unfavourable prognostic sign?
after 3 months
which features of ALL carry a poor prognosis?
- hypodiploidy (<44 chromosomes)
- the Ph translocation t(9;22)
- most translocations involving 11q23 (MLL)
the presence of MRD in children after how many days of treatment is an unfavourable prognostic sign?
29 days
lumbar puncture for CSF examination is important for what?
disease staging
differential diagnosis for ALL includes?
- AML
- aplastic anaemia
- marrow infiltration by other malignancies
- infections like infectious mono and pertussis
- juvenile arthritis
- immune thrombocytic purpura
CAR-T cell therapy is approved for patients with what?
refractory B-ALL or large B cell non-hodgkin lymphoma expressing CD19
which drug may also help in cases if ALL that express CD22?
inotuzumab ozogamicin
which ALL drug is a CD19 antibody conjugated to an antibody against CD3?
blinatumomab
what is necessary after (CAR)‐T cell therapy for relapsed acute lymphoblastic leukaemia?
lifelong immunoglobulin replacement therapy
what is the most common site of extramedullary relapse in ALL?
CNS
which marker is most commonly expressed on the surface of blast cells in B-cell ALL?
CD19
