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 haematological malignancy characterised by clonal proliferation of immature lymphoid precursors (lymphoblasts).
It is the most common childhood cancer πΆ, peaking at 2β4 years, but also occurs in adults with worse outcomes.
Childhood ALL is now highly curable with modern regimens (5-year survival >85% π), while adult ALL remains more challenging.
About
- Accounts for ~25% of all childhood cancers ποΈ
- Boys slightly > girls (βοΈ>βοΈ)
- Represents clonal expansion of immature B- or T-lymphoblasts in the bone marrow π§¬
Risk Factors
- Most cases: no identifiable cause β
- Genetic: Down syndrome (β¬οΈ risk), ataxia-telangiectasia, Fanconi anaemia
- Environmental: ionising radiation β’οΈ, pesticide exposure πΏ
Pathophysiology
- Genetic lesions β unchecked proliferation of lymphoblasts π
- Marrow infiltration:
- Anaemia β fatigue π΄
- Thrombocytopenia β bleeding/bruising π©Έ
- Neutropenia β infections π€
- Extramedullary spread: lymphadenopathy, hepatosplenomegaly, CNS, mediastinal mass (esp. T-ALL) π§ π«
- Markers:
- B-ALL β CD19, CD10, CD79a, TdT
- T-ALL β CD3, CD7
WHO & FAB Classification
- WHO: Precursor B-ALL, T-ALL, Mature B-ALL (Burkitt-type)
- FAB:
- L1 β small uniform blasts π¬
- L2 β larger, variable blasts with nucleoli
- L3 β Burkitt type (deeply basophilic, vacuolated) π§«
Clinical Features
- Bone marrow failure: fatigue, fever, bleeding/bruising π
- Organ infiltration: hepatosplenomegaly, lymphadenopathy π₯
- CNS involvement: headache, cranial nerve palsies π§
- T-ALL: mediastinal mass β stridor/SVC obstruction π¨
- B-symptoms: fever, sweats, weight loss ππ₯βοΈ
Investigations
- FBC: cytopenias + blasts seen π
- Blood film: lymphoblasts (high N:C ratio)
- Bone marrow biopsy: >20% blasts β
- Flow cytometry: B vs T lineage typing
- Cytogenetics:
- t(12;21) ETV6-RUNX1 β good prognosis π
- t(9;22) BCR-ABL (Ph+) β poor prognosis β οΈ
- Hyperdiploidy β good β
- Hypodiploidy β poor β
- Lumbar puncture: CNS staging π
Differential Diagnosis
- Lymphoblastic lymphoma (<30% blasts in marrow)
- Aplastic anaemia (pancytopenia but no blasts)
- AML (myeloperoxidase+ granules) π§ͺ
Management
- Resuscitation: ABC, tumour lysis prevention (allopurinol/rasburicase π§)
- Supportive care: transfusions, antibiotics, antifungals π©Έπ
- Chemotherapy (UKALL protocols):
- Induction: vincristine, steroids, asparaginase, Β± anthracycline
- Consolidation: high-dose methotrexate, cytarabine
- CNS prophylaxis: intrathecal methotrexate π
- Maintenance: 6-mercaptopurine + methotrexate (2β3 yrs)
- Targeted therapy: imatinib/dasatinib for Ph+ ALL π―
- Immunotherapy: CAR-T (tisagenlecleucel) π§¬, blinatumomab (BiTE antibody)
- Allogeneic SCT: in relapse or high-risk patients π±
Prognosis
- Good: Age 1β10, low WBC, hyperdiploidy, ETV6-RUNX1 π
- Poor: Infants <1 πΆ, adults >50 π΄, WBC >50,000, Ph+, MLL rearrangements β οΈ
- Survival: Children >85% cured, adults 40β50% 5-yr survival π