Acute Lymphoblastic Leukaemia

Question 1

What age group is usually affected by ALL and how common is it?

Answer 1

It is the most common childhood cancer, and accounts for 80% of childhood leukaemia.

Most commonly occurs in 2-5 year olds.

If it occurs before the age of 1 or after the age of 10 it is high risk and has a worse prognosis.

Question 2

Which cells are affected in ALL?

Answer 2

Malignancy of the lymphoid progenitor cells.

It usually B cell in origin but can be of a T cell origin.

Question 3

How does ALL present (systems)?

Answer 3

General:
Malaise and anorexia
Lympathendopathy

Bone Marrow:
Anaemia (pallor, dizziness, dysopnea, tachycardia)
Recurrent/severe infections (fever of unknown origin)
Easy bruising/bleeding (may have petechiae)

Bone:
Unusual bone/joint pain

Abdo:
Hepato-splenomegaly
Early satiety (due to pressure on stomach from the spleen)

CNS: (in CNS metastasis)
Headache
Irritability or altered mental status 
Neck stiffness
CN palsies

Question 4

What investigations should be done in suspected ALL?

Answer 4

Bloods:
FBC
Blood film (normal if leukaemia is confined to the BM)
Clotting
Lactate Dehydrogenase (will be raised with fast turnover of cells)
LFT’s and U/e’s before chemo.

Biopsy:
Bone Marrow aspiration and biopsy
(Needed for diagnosis but also to look for particular immunological and cytogenetic markers to tailor treatment)

Imaging:
CXR to identify metastases (lung mets are common in T cell disease)

Question 5

What is the immediate treatment of a patient with respect to transfusions?

Answer 5

Red cell and platelet transfusions are used to treat the symptoms of anaemia and thrombocytopenia.

These should be done before any invasive investigations (bone marrow biopsy, LP)

Question 6

What is tumour lysis syndrome and how is it managed?

Answer 6

During chemotherapy due to the lysis of cancer cells patients may develop tumour lysis syndrome and the following metabolic derangement:

• Hyperuricaemia
• Hyperphosphataemia
• Hypocalcaemia
• Hyperkalaemia

This must be closely monitored for and treated with careful IV fluids and allopurinol (for the hyperaemia)

Note: Hypocalcaemia occurs as due to the high levels of phosphate the calcium forms the calcium phosphate precipitate.

Question 7

Roughly outline the treatment regimen for patients with ALL?

Answer 7

Remission induction.
Intensification.
Maintenance.

Eradication to induce remission aka eradication of the leukaemic blast cells and restoration of normal marrow function. Four weeks of combination chemotherapy is given and current induction treatment schedules achieve remission rates of 95%.

Intensification – a block of intensive chemotherapy is given to consolidate remission and this improves cure rate.
Note: cytotoxic drugs penetrate poorly into the CNS, therefore intrathecal chemo is given to prevent CNS relapse.

Maintenance therapy – chemotherapy of modest intensity is continued over a relatively long period of time, up to 3 years from diagnosis. (roughly 1 year longer in males)

Co- trimoxazole prophylaxis is given routinely to prevent pneumocystis carinii pneumonia.

Question 8

How is relapse managed?

Answer 8

Depending on the severity of the relapse:

Intensive chemo or full body irradiation followed by bone marrow transplant.

Question 9

Describe the prognostic factors used in staging ALL?

Answer 9

Can be classified by the types of tumour cell:

L1: small uniform cell
L2: large varied cells
L3: large varied cells with vacuoles

It is also classified as high or low risk based on the following factors:

Age:
High risk = less than 1 year or greater than 10 years

Tumour load (measured by WBC)
High risk = >50 x 109/L

Cytogenetic/molecular genetic abnormalities in tumour cells
e.g. MLL rearrangement

Persistence of leukaemia blasts in the bone marrow after initial chemo

Minimal residual disease assessment (MRD) (submicroscopic levels of leukaemia detected by PCR)
High risk = high levels

Male gender

CNS involvement