23rd July 2024

Acute lymphoblastic leukaemia

Background of ALL

ALL occurs due to clonal proliferation of haematopoietic precursor cells of lymphoid lineage in the BM.

ALL is the most common malignancy in childhood. Peak incidence is between the ages of two and five, with further smaller peaks in the mid-30s and mid-80s. Incidence is higher in males than females.

Approximately 85% of ALL is of B-cell lineage and 15% is of T-cell lineage.

The exact cause is not known, but there are known associated contributing factors. These include genetic factors (higher likelihood of development between monozygotic twins than singleton siblings) and pre-existing genetic syndromes (e.g. Down syndrome, Klinefelter’s syndrome, ataxia-telangiectasia). Contributing environmental factors include radiation and smoking exposure.

Presentation and diagnosis of ALL

The presenting signs and symptoms are from BM failure (see acute myeloid leukaemia).

In addition, children can often present with hepatomegaly and/or splenomegaly and lymphadenopathy.

As with AML, diagnosis requires blood tests, blood film and BM biopsy (for immunophenotyping, cytogenetics and molecular analysis).

MRCP Part 2 - Bone marrow aspirate smear of acute lymphoblastic leukaemia

Image Source: Wikimedia Commons (2007). Acute leukemia-ALL, Licensed under a creative commons licence. Available for free at: https://en.wikipedia.org/wiki/Acute_lymphoblastic_leukemia#/media/File:Acute_leukemia-ALL.jpg (Accessed: 16 January 2024).

Differentiating between AML and ALL

	AML	ALL
Epidemiology	Older patients (generally >60)	Children (<10)
Presentation	Hepatosplenomegaly and lymphadenopathy not a prominent feature	Generally present with hepatosplenomegaly or lymphadenopathy
Blood film morphology	Large cells Variable cytoplasm (often larger amounts) Large, regular nuclei (often round) Auer rods (pathognomonic)	Large cells Scant to moderate cytoplasm Irregular/convoluted nuclei No Auer rods
Immunophenotyping	MPO, CD33, CD34	B-cell lineage: CD19, HLA-DR T-cell lineage: CD3, CD7, CD4 Both lineages: TdT

Management and prognosis of ALL

Treatment of ALL consists of four main stages:

Remission induction: generally a four drug regimen.
Consolidation therapy: several combinations, aiming to use drugs that differ in mechanism of action to those used for induction.
CNS prophylaxis (or treatment if there is CNS involvement): intrathecal CNS prophylaxis is given alongside all stages of treatment to reduce risk of relapse with leukaemic meningitis.
Stem cell transplant/maintenance therapy: SCT is preferred in patients after consolidation therapy who are at high risk of relapse. Maintenance therapy is recommended in patients who are high risk, but ineligible for SCT, or who are at standard risk for relapse.

Prognosis is significantly worse in adults than in children. Cure rates in children are high at around 80%, whereas 35-40% of adults treated with intensive chemotherapy survive two years. Prognostic factors include:


Favourable prognostic factors	Age 1-9 years Cytogenetics, e.g. t(12;21) High hyperdiploidy (>50 chromosomes)
Poor prognostic factors	In children: age <1 or >10 years; in adults: age >35 years WCC >30 x109/L (for B-cell ALL), >100 x109/L (for T-cell ALL) WCC >50 x109/L for children Pre-morbid myelodysplastic syndrome or myeloproliferative neoplasm Cytogenetics, e.g. t(9;22), MLL translocations or abnormal 17p

Favourable prognostic factors

Age 1-9 years

Cytogenetics, e.g. t(12;21)

High hyperdiploidy (>50 chromosomes)

Poor prognostic factors

In children: age <1 or >10 years; in adults: age >35 years

WCC >30 x109/L (for B-cell ALL), >100 x109/L (for T-cell ALL)

WCC >50 x109/L for children

Pre-morbid myelodysplastic syndrome or myeloproliferative neoplasm

Cytogenetics, e.g. t(9;22), MLL translocations or abnormal 17p