Leukemia Flashcards
Leukemias
malignant neoplasms of the haemopoietic stem cells, characterised by diffuse replacement of the bone marrow by neoplastic cells
Classification
by lineage and degree of maturity of the leukaemic clone
which diseases is the philadelphia (Ph) chromosome associated with?
found in 95% of cases with CML and some patients with AML
what happens in the Ph chromosome?
the long arm of ch22 is shortened by reciprocal translocation to the long arm of ch9 (t(9;22))
210-kDa fusion protein product of the resulting ‘fusion’ gene, BCR-ABL, has tyrosine kinase activity, and enhanced phosphorylating activity compared with the normal protein –> altered cell growth, stromal attachment and apoptosis
uncontrolled cell division
environmental factors
chemical e.g. industrial benzene compounds
drugs e.g AML occurs after Tx with alkylating agents e.g. melphalan
radiation exposure
What are the acute leukaemia characterised by?
clonal proliferation of myeloid or lymphoid precursors with reduced capacity to differentiate into more mature cellular elements
accumulation of laekaemic cells in the BM, peripheral blood and other tissues, with a reduction in RBCs, platelets and neutrophils
epidemiology acute leukemia
ALL is predominantly a disease of childhood (L for little)
AML seen most frequently in older adults (M for mature)
clinical features acute leukemia
resulting from marrow failure:
- anaemia
- bleeding
- infection e.g. sore throat and pneumonia
? peripheral lymphadenopathy and hepatosplenomegaly
Ix acute leukemia
peripheral blood film
BM aspirate
what does the blood count show in acute leukemia
anaemia and thrombocytopenia
white cell count is usually raised, but may be normal or low
what does the blood film show in acute leukemia
characteristic blast cells
what histological feature is characteristic of AML?
Auer rods (a rod-like conglomeration of granules in the cytoplasm)
what does BM aspirate show in acute leukaemia?
increased cellularity, with a high % of abnormal lymphoid or myeloid blast cells
Mx acute laeukemia
induction chemo to return peripheral blood and BM to normal
supportive care prior to treatment: correction of anaemia and thrombocytopenia, treat infection with IV antibiotics
proposed pathogenesis of AML
myeoblasts are stopped from differentiating further.
2 mutations?
one –> rapid proliferation of myeoblast and its resistance to apoptose
2nd: blocks its further differentiation
what must BM biopsy show for AML to be diagnosed?
20% blast cells
Methods of genetic testing
FISH
PCR
Tx AML
walking exercises to reduce fatigue
supportive care
chemo e.g. cytarabine and daunorubicin
HLA sibling matched allogenic bone marrow transplant
Why does a bone marrow transplant allow for very aggressive chemo?
due to reduced risk of bone marrow failure
Acute lymphoblastic leukaemia prognosis
Children- excellent: 80% cured at 5yr. Most common paediatric malignancy
Adults- worse with age: 30% being cured
How does Tx differ in AML to ALL
ALL has the propensity to involve the CNS, so Tx includes prophylactic intrathecal drugs: methotrexate or cytosine arabinoside (cytarabine)
Cranial irradiation sometimes used
Significance of Ph chromosome in ALL?
It is a poor prognostic factor
Its more common in adults
Who does chronic myeloid leukaemia occur in?
+ survival rate
middle aged
characterised by the presence of the Philadelphia (Ph) chromosome
survival median: 5-6yrs
Chronic phase of CML
Lasts 3-4 yrs if untreated
- insidious onset: fever, wt loss, sweating and Sx of anaemia. massive splenomegaly
Followed by blast transformation, with development of AML and commonly, rapid death
Or could transforms to myelofibrosis, death ensuing from BMF
