Paediatrics: Acute lymphoblastic leukaemia

Acute lymphoblastic leukaemia

This is the most common malignancy in childhood. It arises from malig-nant proliferation of ‘pre-B’ (common ALL) or T-cell lymphoid precursors. The cause is unknown, but in a minority it is associated with chromoso-mal aberrations. Possible links to patterns of childhood infection acting as a trigger have been hypothesized.

·  ALL accounts for 25% of all childhood malignancies.

·  Commonly presents in young children aged 2–6yrs.

Presentation

Typically with a short history (days or weeks), and with symptoms and signs reflecting pancytopenia, bone marrow expansion, and lymphadenop-athy. Includes petechiae, bruising, pallor, tiredness, bone/joint pain/swell-ing, limp, lymphadenopathy, airway obstruction, and pleural effusion.

Specific diagnostic tests

·  Bone marrow: morphology; immunophenotype; cytogenetics.

·  CSF for cytospin (CNS rarely involved at first diagnosis).

·  Clinical examination of testes in boys for inappropriate swelling.

·  CXR for mediastinal mass.

Outline of ‘standard’ treatment

Induction (4wks)

·  Steroids (dexamethasone or prednisolone) throughout induction

·  Weekly IV vincristine

·  IM L-asparaginase (e.g. 9 doses in 3wks or 2 doses of pegylated asparaginase)

·  IV daunorubicin (2–4 doses, in intermediate and high risk cases)

·  Intrathecal (IT) methotrexate (day 18)

Note Tumour lysis syndrome is a significant risk Consolidation CNS-directed therapy

·  Low risk cases: 4-weekly doses of IT methotrexate and continuous oral mercaptopurine.

·  Higher risk cases: add IV cyclophosphamide, cytarabine.

·  CNS-radiotherapy only for CNS +ve cases

Maintenance

Continuation treatment for at least 2yrs (3yrs for boys)

·  Daily 6-mercaptopurine (6MP), weekly oral methotrexate (doses titrated according to blood count)

·  4-weekly vincristine IV bolus and 5-day pulses of oral dexamethasone

·  12-weekly IT methotrexate

Intensive blocks of chemotherapy

One or two blocks of 8wks duration, interrupting 1st year of mainte-nance. Combinations of oral steroid, vincristine, doxorubicin, cyclophos-phamide, cytarabine, and L-asparaginase

Prognosis

Overall survival is approximately 80% with current treatment. Adverse prognostic factors include:

·Male gender.

·Age <2yrs or >10yrs.

·High WCC at diagnosis.

·Unfavourable cytogenetics: Philadelphia chromosome—t(9;22); MLL gene rearrangements (e.g. t(4;11) in infants); AML1 amplification;

·Poor response to induction and failure to remit by day 28.

·High level of minimal residual disease (MRD) at 28 days.

Mature B-cell ALL (Burkitt’s type, L3 morphology)

Once considered a high-risk group, outlook is similar to that in stand-ard risk ALL now that patients are treated with intensive chemotherapy according to strategy for B-cell non-Hodgkins lymphoma.

Relapsed ALL

Extramedullary relapse (mainly CNS, testes) may present without bone marrow disease. Treatment is stratified according to risk factors, which include:

·Time from first diagnosis (risk reduces with time).

·Extramedullary relapse (lower risk, particularly if isolated).

·Minimal residual disease (MRD) status after re-induction (–ve status reduces risk).

Treatment

·Intensive re-induction and consolidation for all risk groups.

·Low risk: 2yrs of continuing conventional chemotherapy.

·High risk: BMT allograft.

·Intermediate risk: the role of BMT in this group is unclear; it may be based on minimal residual disease and/or availability of matched donor.

·Radiotherapy for extramedullary disease: given as a boost for those receiving total body irradiation (TBI) for BMT.

Prognosis

Long-term survival varies: 10–90% depending on risk (e.g. 90% in those with isolated extramedullary relapse more than 2yrs off treatment).