Makindo Medical Notes

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 👶, peaking at 2–4 years, but also occurs in adults with worse outcomes. Childhood ALL is now highly curable with modern regimens (5-year survival >85% 🎉), while adult ALL remains more challenging.

About

• Accounts for ~25% of all childhood cancers 🎗️
• Boys slightly > girls (♂️>♀️)
• Represents clonal expansion of immature B- or T-lymphoblasts in the bone marrow 🧬

Risk Factors

• Most cases: no identifiable cause ❓
• Genetic: Down syndrome (⬆️ risk), ataxia-telangiectasia, Fanconi anaemia
• Environmental: ionising radiation ☢️, pesticide exposure 🌿

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

WHO & FAB Classification

• WHO: Precursor B-ALL, T-ALL, Mature B-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 seen 🔍
• 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 (<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 (UKALL protocols):
  • 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 (BiTE antibody)
• 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% cured, adults 40–50% 5-yr survival 📊

🧑‍⚕️ Case Examples — Acute Lymphoblastic Leukaemia (ALL)

• Case 1 (Child with bone marrow failure): 👧 A 6-year-old girl presents with 2 weeks of pallor, easy bruising, and recurrent nosebleeds. Exam shows petechiae and hepatosplenomegaly. Bloods: Hb 7 g/dL, platelets 25 × 10⁹/L, WCC 1.2 × 10⁹/L. Peripheral smear: blasts present. Analysis: Pancytopenia due to marrow infiltration is a common presentation in paediatric ALL. Diagnosis: Childhood ALL. Management: Urgent bone marrow biopsy confirms diagnosis. Begin induction chemotherapy as per national protocol (e.g., UKALL). Central venous access inserted. Supportive care with transfusions and antibiotics.
• Case 2 (Teenager with mediastinal mass): 🫁 A 15-year-old boy presents with dyspnoea, facial swelling, and venous congestion. Chest X-ray shows a large anterior mediastinal mass. Bloods: high WCC, abnormal lymphoblasts. Analysis: T-cell ALL often presents with mediastinal mass causing SVC obstruction. Diagnosis: T-cell Acute Lymphoblastic Leukaemia. Management: Stabilise airway, avoid central lines due to risk of mediastinal compression, start corticosteroids to reduce tumour bulk, followed by multi-agent chemotherapy. Oncology team monitors for tumour lysis syndrome (TLS).
• Case 3 (Adult ALL with CNS involvement): 🧠 A 35-year-old man presents with headache, blurred vision, and vomiting. Exam shows papilloedema and cranial nerve palsy. Bloods: WCC 60 × 10⁹/L, blasts on smear. CSF positive for lymphoblasts. Analysis: Adults with ALL may present with CNS infiltration at diagnosis. Diagnosis: Acute Lymphoblastic Leukaemia with CNS involvement. Management: Start systemic chemotherapy plus intrathecal methotrexate for CNS prophylaxis/treatment. Monitor ICP and manage with steroids if needed. Consider allogeneic stem cell transplant if high risk.