Acute lymphoblastic leukaemia
(ALL) can occur at any age but has a peak incidence between 2 - 10 years. It is
- bone marrow failure
- thymic enlargement in T-lineage ALL
- bone pain which may be associated with radiological change and fracture
- tendency to relapse in the CNS and testis.
Blast morphology is variable - some are small with high nuclear:cytoplasmic
ratios and indistinct nucleoli (so-called L1 blasts) while others are larger
with more prominent nucleoli and more abundant cytoplasm (L2). Blast morphology
does not correlate with cell lineage and cytochemistry is of little value.
ALL. Bone marrow. Complete replacement by
small/medium sized blasts with scanty cytoplasm and round nuclei with
dense chromatin (FAB L1 type, common-ALL phenotype).
ALL. Bone marrow. Pleiomorphic blasts with variable
amounts of cytoplasm, twisted irregular nuclei and multiple indistinct
nucleoli. (FAB L2 type, common-ALL phenotype).
Burkitt lymphoma, leukaemic phase. Bone marrow.
Deeply basophilic blasts with dense nuclear chromatin and multiple
cytoplasmic vacuoles. t(8;14) present.
ALL. Peripheral blood. Large blasts with convoluted
nuclei and basophilic cytoplasm. (T-ALL
ALL is derived from precursor lymphocytes that are undergoing antigen
receptor gene (Ig and TCR) rearrangement.
B-lineage ALLThe precursor nature of the cells is established by
demonstrating lack of surface Ig, the presence of nuclear Tdt and sometimes the
expression of CD34. Subclassification is as follows:
- Pre-pre B-ALL: CD19+ CD10- cytoplasmic mu
heavy chain negative.
- Common ALL: CD19+ CD10+ cytoplasmic mu
present in <20% of cells
- Pre B-ALL: CD19+ CD10+ cytoplasmic mu present
in >20% of cells
- Blasts of all subgroups will express cytoplasmic CD22 and CD79b.
Two-colour immunophenotypic profile of common-ALL:
blast cells positive for CD34 and CD10.
Pre pre-B ALL blast cells lack expression of
T-lineage ALLThe precursor nature of the cells is established by
demonstrating Tdt and sometimes CD34 positivity and the lack of surface TCR/CD3.
T-cell lineage is demonstrated by the expression of CD7 and/or CD1a. Expression
of the other pan-T cell markers is variable.
Hyperdiploidy is common. A number of
balanced translocations have been identified in ALL:
- t(12;21) - this is the commonest translocation in ALL (30% of cases). It
results in the TEL-AML fusion gene and is primarily associated with the common
- t(9;22) - this is commoner in adults and is associated with a very poor
- t(4;11) - this translocation results in the MLL-AF4 fusion gene. It is
associated with pre-pre B-ALL and is associated with a poor prognosis[5,6].
- t(1;19) - associated with pre-B ALL and results in the formation of the
E2A-PBX fusion gene[7,8].
These translocations are demonstrable by RT-PCR techniques.
TAL-1 deregulation is the commonest genetic abnormality in T-ALL. This may
occur as the result of the t(1;14) or more commonly due to chromosome 1p32
The following are poor
prognostic factors in ALL:
The treatment of ALL consists of
the following "phases":
- age <1 year and >10 years
- male sex
- CNS disease at presentation
- high white cell count
- Remission induction - vincristine, prednisolone, daunorubicin,
- Consolidation - various combinations of chemotherapeutic agents.
- CNS directed therapy - high dose systemic and intrathecal methotrexate.
- Maintenance therapy - vincristine, prednisolone, mercaptopurine and
methotrexate for 2 years.
Childhood ALL is associated with 75% long term survival. Minimal residual
disease assessment using PCR based strategies appear to be able to predict
relapse although they are not yet in routine clinical use. Allogeneic
transplantation is the treatment of choice at relapse.
The outlook in adult ALL is poor with approximately 20% long-term survivors.
Allogeneic transplantation is advisable in first remission.