About This Page
This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
The Bottom Line
- Commonest cancer in children (peak age 2-5 years) — also occurs in adults (second peak >60 years)
- Presentation: pancytopenia symptoms (anaemia, infection, bleeding) + bone pain + hepatosplenomegaly + lymphadenopathy
- Diagnosis: blood film shows lymphoblasts; bone marrow biopsy >20% blasts is diagnostic. Immunophenotyping (B-cell or T-cell ALL) essential
- Philadelphia chromosome (BCR-ABL1 t(9;22)) present in ~25% of adult ALL — poor prognosis but responds to tyrosine kinase inhibitors
- Treatment: intensive multi-agent chemotherapy (induction → consolidation → maintenance). CNS-directed prophylaxis essential. Childhood ALL cure rate >90%
Overview
Acute lymphoblastic leukaemia (ALL) is a malignant clonal proliferation of lymphoid precursor cells (lymphoblasts) in the bone marrow, blood, and extramedullary sites. It is classified by immunophenotype: B-cell ALL (~85% of childhood cases) and T-cell ALL (~15%). The accumulation of lymphoblasts in the marrow suppresses normal haematopoiesis, causing pancytopenia. ALL has a particular predilection for CNS involvement — hence CNS prophylaxis is a mandatory component of treatment.
Epidemiology
ALL is the commonest childhood cancer, accounting for ~25% of all paediatric malignancies. The peak incidence is age 2-5 years. Boys are slightly more commonly affected. In the UK, approximately 650-700 cases are diagnosed annually in all ages. There is a second smaller peak in adults over 60. Risk factors include Down syndrome (20-fold increased risk), prior radiation exposure, and certain genetic conditions (ataxia telangiectasia, Bloom syndrome). Childhood ALL has dramatically improved outcomes — 5-year survival now exceeds 90% in children.
Clinical Features
Symptoms
Fatigue, pallor (anaemia from marrow failure)
Recurrent infections, persistent fever (neutropenia)
Easy bruising, petechiae, epistaxis, bleeding gums (thrombocytopenia)
Bone and joint pain (marrow infiltration) — a child refusing to walk should raise suspicion
Weight loss, night sweats, malaise
Headache, vomiting, visual disturbance (CNS involvement)
Testicular swelling (testicular infiltration — sanctuary site)
Signs
Pallor, petechiae, purpura
Hepatosplenomegaly (extramedullary disease)
Generalised lymphadenopathy
Mediastinal mass (T-cell ALL — may cause SVC obstruction)
Cranial nerve palsies, papilloedema (CNS disease)
Testicular enlargement
Investigations
First-line
FBCPancytopenia common. WCC may be low, normal, or very high (hyperleukocytosis >100 × 10⁹/L — medical emergency)
Blood filmCirculating lymphoblasts — small cells with high nuclear:cytoplasmic ratio, scant cytoplasm, fine chromatin
Bone marrow aspirate and trephineDiagnostic: ≥20% lymphoblasts. Sent for morphology, immunophenotyping, cytogenetics, and molecular analysis
Second-line
Immunophenotyping (flow cytometry)Essential to classify: B-ALL (CD19+, CD10+, CD20+) or T-ALL (CD2+, CD3+, CD7+)
Cytogenetics and FISHPhiladelphia chromosome t(9;22) BCR-ABL1 (25% adults, 3-5% children — poor prognosis). t(12;21) ETV6-RUNX1 (good prognosis in children). Hyperdiploidy (good prognosis)
LDH, urate, K+, Ca2+, PO4, creatinineBaseline tumour lysis syndrome markers — check before starting treatment
Specialist
Lumbar puncture with cytospinMandatory at diagnosis — to detect CNS involvement. Blasts in CSF = CNS disease requiring intensified CNS-directed treatment
CT chestIf T-ALL suspected — look for mediastinal/thymic mass
Minimal residual disease (MRD)Flow cytometry or PCR at defined timepoints during treatment — key prognostic indicator and guides treatment intensity
1
Emergency management
- Hyperleukocytosis (WCC >100): leucodepletion, aggressive hydration, rasburicase for tumour lysis prophylaxis
- Neutropenic sepsis: immediate IV antibiotics (piperacillin-tazobactam per local protocol)
- Mediastinal mass: avoid general anaesthesia (airway compression risk), urgent steroid therapy
2
Induction chemotherapy
- Multi-agent protocol: vincristine, dexamethasone, asparaginase, ± daunorubicin
- Aim: achieve complete remission (CR) with MRD negativity
- Intrathecal methotrexate for CNS prophylaxis — given from induction throughout treatment
3
Consolidation and maintenance
- Consolidation: intensification blocks with cytarabine, methotrexate, cyclophosphamide
- Maintenance: daily 6-mercaptopurine + weekly methotrexate for 2-3 years total treatment duration
- Philadelphia-positive ALL: add tyrosine kinase inhibitor (imatinib or dasatinib) throughout
4
Allogeneic stem cell transplant
- Indicated for very high-risk disease, poor MRD response, or relapse
- Philadelphia-positive ALL in adults: often transplanted in first remission
5
Relapsed/refractory ALL
- CAR-T cell therapy (tisagenlecleucel) — NICE-approved for B-ALL in children and young adults
- Blinatumomab (bispecific T-cell engager)
- Inotuzumab ozogamicin (anti-CD22 antibody-drug conjugate)
Complications
- Tumour lysis syndrome: Massive cell lysis at treatment initiation → hyperkalaemia, hyperuricaemia, hyperphosphataemia, hypocalcaemia, AKI
- Neutropenic sepsis: Potentially fatal — the major treatment-related cause of death
- CNS relapse: Leukaemic infiltration of meninges — hence mandatory CNS prophylaxis
- Late effects of treatment: Avascular necrosis (steroids), cardiomyopathy (anthracyclines), secondary malignancies, infertility, neurocognitive effects
UKMLA Exam Tips
- 1Child aged 2-5 with pancytopenia + bone pain + hepatosplenomegaly = think ALL until proven otherwise
- 2ALL is the COMMONEST childhood cancer. AML is more common in adults
- 3Philadelphia chromosome t(9;22) = BCR-ABL1 = poor prognosis in ALL but responds to TKIs (imatinib)
- 4CNS involvement is characteristic of ALL — always need LP at diagnosis and intrathecal chemo for prophylaxis
- 5Mediastinal mass = T-cell ALL. Risk of SVC obstruction and airway compromise under GA
- 6Cure rate in childhood ALL now exceeds 90% — one of the great success stories of haematology
- 7Tumour lysis syndrome prophylaxis: aggressive hydration + rasburicase (converts urate to allantoin)
practicetest your knowledge on allApply what you've learnt with UKMLA-style questions from the iatroX Q-Bank — haematology and beyond.
open q-bank