Related Subjects:
|Leukaemias in General
|Acute Promyelocytic Leukaemia
|Acute Myeloblastic Leukaemia (AML)
|Acute Lymphoblastic Leukaemia (ALL)
|Chronic Lymphocytic leukaemia (CLL)
|Chronic Myeloid Leukaemia (CML)
|Hairy Cell Leukaemia
|Differentiation syndrome
|Tretinoin (All-trans-retinoic acid (ATRA) )
|Haemolytic anaemia
|Immune (Idiopathic) Thrombocytopenic Purpura (ITP)
Acute Lymphoblastic Leukaemia (ALL) 🩸 is an aggressive cancer of the blood and bone marrow characterized by uncontrolled lymphoblast proliferation.
👶🧑 Who it affects
- Most common childhood cancer, peaking at 2–4 years
- Adults can be affected; outcomes are generally poorer than in children
⚠️ Why it happens (Risk factors)
- Most cases: no identifiable cause
- Genetic: Down syndrome, ataxia-telangiectasia, Fanconi anaemia
- Environmental: ionising radiation, pesticide exposure
🔬 How it develops (Pathophysiology)
- Genetic lesions → unchecked proliferation of lymphoblasts
- Marrow infiltration:
- Anaemia → fatigue
- Thrombocytopenia → bleeding/bruising
- Neutropenia → infections
- Extramedullary spread: lymphadenopathy, hepatosplenomegaly, CNS, mediastinal mass (esp. T-ALL)
- Markers:
- B-ALL → CD19, CD10, CD79a, TdT
- T-ALL → CD3, CD7
🗂️ Classification
- WHO: precursor B-ALL, T-ALL, Burkitt-type
- FAB:
- L1 → small uniform blasts
- L2 → larger, variable blasts with nucleoli
- L3 → Burkitt-type (deeply basophilic, vacuolated)
🩺 Clinical Features
- Bone marrow failure: fatigue, fever, bleeding/bruising
- Organ infiltration: hepatosplenomegaly, lymphadenopathy
- CNS involvement: headache, cranial nerve palsies
- T-ALL: mediastinal mass → stridor/SVC obstruction
- B-symptoms: fever, sweats, weight loss
🔎 Investigations
- FBC: cytopenias + blasts
- Blood film: lymphoblasts (high N:C ratio)
- Bone marrow biopsy: >20% blasts
- Flow cytometry: B vs T lineage typing
- Cytogenetics:
- t(12;21) ETV6-RUNX1 → good prognosis
- t(9;22) BCR-ABL (Ph+) → poor prognosis
- Hyperdiploidy → good
- Hypodiploidy → poor
- Lumbar puncture: CNS staging
⚖️ Differential Diagnosis
- Lymphoblastic lymphoma (less than 30% blasts in marrow)
- Aplastic anaemia (pancytopenia but no blasts)
- AML (myeloperoxidase+ granules)
💊 Management
- Resuscitation: ABC, tumour lysis prevention (allopurinol/rasburicase)
- Supportive care: transfusions, antibiotics, antifungals
- Chemotherapy (risk-adapted):
- Induction: vincristine, steroids, asparaginase, ± anthracycline
- Consolidation: high-dose methotrexate, cytarabine
- CNS prophylaxis: intrathecal methotrexate
- Maintenance: 6-mercaptopurine + methotrexate (2–3 yrs)
- Targeted therapy: imatinib/dasatinib for Ph+ ALL
- Immunotherapy: CAR-T (tisagenlecleucel), blinatumomab
- Allogeneic SCT: in relapse or high-risk patients
🏁 Prognosis
- Good: Age 1–10, low WBC, hyperdiploidy, ETV6-RUNX1
- Poor: Infants <1, adults >50, WBC >50,000, Ph+, MLL rearrangements
- Survival: Children >85% 5-year; adults lower
📚 Case Examples - Acute Lymphoblastic Leukaemia (ALL)
-
Case 1 (Child with bone marrow failure): A 6-year-old girl presents with pallor, easy bruising, nosebleeds; exam shows petechiae and hepatosplenomegaly. Hb 7 g/dL, platelets 25 × 10&sup9;/L, WCC 1.2 × 10&sup9;/L. Peripheral smear: blasts. Analysis: Pancytopenia due to marrow infiltration. Diagnosis: Childhood ALL. Management: urgent bone marrow biopsy; induction chemotherapy per national protocol; central venous access; supportive care.
-
Case 2 (Teenager with mediastinal mass): A 15-year-old with dyspnea, facial swelling, venous congestion. CXR: large anterior mediastinal mass. High WCC, abnormal lymphoblasts. Analysis: T-cell ALL often with mediastinal mass causing SVC obstruction. Management: airway stabilization, avoid central lines, start corticosteroids to reduce mass, then multi-agent chemotherapy; monitor for TLS.
-
Case 3 (Adult ALL with CNS involvement): A 35-year-old with headache, blurred vision, vomiting; papilledema; WCC 60 × 10&sup9;/L; CSF positive for lymphoblasts. Analysis: CNS involvement possible at diagnosis. Management: systemic chemotherapy plus intrathecal methotrexate; monitor ICP; steroids as needed; consider allogeneic SCT if high risk.
📋 NICE Guidelines & References
