4.02 Leukaemia

Heavy infiltrate (blue) and absence of fat spaces

None- it is a feature of all leukaemias

Ulceration is from tissue breakdown in the presence of neutropenia
Cavitating lung lesions form after a fungal infection of a neutropenic person

Acute myeloid leukaemia

A clone

PCR- polymerase chain reaction. Seen in B cells sharing immunoglogulin gene rearrangement (get single line, not smear)
Flow cytometry- stain B cells with monoclonal antibody and see a population skew towards kappa or lambda

AML- delicate chromatin, much cytoplasm, fine granules in cytoplasm of myoblast that can coalesce into little rods (Auer rods)
ALL- clumped chromatin, scant cytoplasm, no granules

Most are granulocyte differentiation M0, M1, M2, M3 (M3, APML, is an emergency, recognised by heavy granules is cytoplasm)
Monocytic differentiation M4, M5
Erythroid differentiation M6
Magekaryocytic differentiation M7

Most are L1, but there are also L2 and L3

It is frequently associated with disseminated intravascular coagulation (DIC) that cn be rapidly fatal in the initial week of therapy

Typical translocation is the 15,17 translocation (PML/RARalpha fusion gene)

The PML/RARalpha fusion gene product is a protein which is the target to therapy called All-trans-retanoic-acid (a vitamin A derivative or retinoid)
Inhibition of cell cycling by ATRA leads to differentiation and cell death

9,22 translocation
Present in:
95% of CML cases
25-30% of adult ALL cases, 2-10% of ALL paediatric cases
Occasionally in AML

The genetic abnormality is a BCR-abl fusion gene, the product of which is a protein with tyrosine-kinase activity. This activity is autonomous and leads to malignant transformation
Imatinib is an inhibitor of the BCR-abl tyrosine kinase

Acute myelomonocytic leukaemia (M4) with very abnormal eosinophils.
Occurs mainly in young adults
Good prognosis! (unlike most AMLs)
High clearance after high dose Cytarabine

1. Induction chemotherapy (using a combination of chemo to induce remission)
2. Consolodation chemotherapy, may be intermediate or intense dose
3. Maintenance therapy in ALL (often for a number of years after remission)
4. Bone marrow transplantation allows the use of much higher doses of chemo than would otherwise be possible in induction chemo.

Childhood ALL: >90% remission, 80% cure
Adult AML and ALL: 60-75% remission, 25-35% cure

-Features all stages of granulocyte development (including mature forms) in peripheral blood and bone marrow
-Splenomegaly
-Either low or high platelet count
-Hyperviscous blood from high white cell count
--Philadelphia chromosome

-Mostly mature lymphocytes in the peripheral blood and bone marrow
-Lymphadenopathy
-Hepatosplenomegaly in advanced cases
-Bone marrow failure in advanced cases
-Autoimmune complications
A distinct pattern of surface proteins is diagnostic (clonal expansion of a single cell)

Targeted therapies oare very effective
Imatinib, transplantation and failing that, chemotherapy

If not symptomatic, then nil
Otherwise, chemotherapy or anti CD-20 antibody

Only in the bone marrow

6-10 days from stem cell to mature cell.
They have a half-time in the blood of 6-7 hours

Bacteria