Acute Lymphoblastic Leukaemia (ALL) is an aggressive haematological malignancy resulting from the clonal proliferation of lymphoid precursor cells (blasts). It is more common in children but also occurs in adults, with prognosis and management differing by age group. Early recognition and timely intervention are key to improving patient outcomes. This guide provides an overview of ALL for junior doctors rotating through haematology.

Understanding ALL

ALL arises from malignant transformation of lymphoid progenitor cells, leading to uncontrolled proliferation and bone marrow failure. It is broadly classified into B-cell ALL (B-ALL) and T-cell ALL (T-ALL) based on the cell lineage of origin. Genetic and molecular features further stratify risk and guide treatment decisions.

Clinical Presentation

Patients with ALL often present with symptoms related to bone marrow failure and organ infiltration:

• Anaemia – Fatigue, pallor, dyspnoea
• Neutropenia – Recurrent infections, fever
• Thrombocytopenia – Easy bruising, petechiae, mucosal bleeding
• Lymphadenopathy & Hepatosplenomegaly – More common in T-ALL
• Mediastinal Mass – T-ALL often presents with a mediastinal mass causing respiratory distress or superior vena cava syndrome (SVCS)
• Neurological Symptoms – Headache, cranial nerve palsies, or seizures due to central nervous system (CNS) involvement

Investigations

A structured approach is crucial when suspecting ALL. Essential investigations include:

• Full Blood Count (FBC) & Blood Film – Shows anaemia, thrombocytopenia, and lymphoblasts.
• Bone Marrow Aspirate & Biopsy – Confirms the diagnosis with >20% lymphoblasts in the marrow.
• Immunophenotyping (Flow Cytometry) – Differentiates B-ALL from T-ALL.
• Cytogenetics & Molecular Testing – Identifies key mutations (e.g., Philadelphia chromosome t(9;22), TEL-AML1, MLL rearrangements) for prognosis and targeted therapy.
• Lumbar Puncture – Evaluates for CNS involvement.
• Coagulation Studies – Important in cases with disseminated intravascular coagulation (DIC).
• Chest X-ray/CT – Checks for a mediastinal mass in T-ALL.

Management

Management of ALL is intensive and consists of several phases:

Supportive Care

• Blood Product Support – Red cell and platelet transfusions as needed.
• Infection Control – Empirical broad-spectrum antibiotics for febrile neutropenia, antifungal and antiviral prophylaxis in high-risk cases.
• Tumour Lysis Syndrome (TLS) Prophylaxis – Hydration, allopurinol, or rasburicase to prevent TLS.

Definitive Treatment

1. Induction Therapy (Aim: Achieve remission)
   • Multi-agent chemotherapy including vincristine, steroids (dexamethasone or prednisolone), anthracyclines (e.g., doxorubicin), and asparaginase.
   • CNS-directed therapy with intrathecal methotrexate.
2. Consolidation (Intensification) Therapy (Aim: Eradicate residual disease)
   • High-dose methotrexate, cytarabine, and additional systemic chemotherapy.
   • Targeted therapies for specific subtypes (e.g., tyrosine kinase inhibitors [TKIs] for Philadelphia chromosome-positive ALL).
3. Maintenance Therapy (Aim: Prevent relapse)
   • Long-term low-intensity chemotherapy (e.g., mercaptopurine, methotrexate) for 2-3 years, especially in paediatric protocols.
4. Stem Cell Transplantation
   • Considered in high-risk or relapsed cases, particularly in adult ALL.
5. Targeted Therapy
   • TKIs (e.g., imatinib, dasatinib) for Philadelphia chromosome-positive ALL.
   • Monoclonal antibodies (e.g., blinatumomab, inotuzumab) for relapsed or refractory disease.

Palliative Care

• In patients who are unfit for intensive therapy due to age, comorbidities, or frailty, supportive care focuses on symptom management and quality of life.
• Transfusions for anaemia-related symptoms, infection control, and pain management are key.
• Clear discussions about goals of care and advanced care planning should be undertaken.

Complications to Watch For

• Febrile Neutropenia – Requires urgent broad-spectrum antibiotics.
• Tumour Lysis Syndrome (TLS) – Can lead to acute kidney injury and metabolic derangements.
• Disseminated Intravascular Coagulation (DIC) – Common in hyperleukocytosis.
• CNS Involvement – Requires intrathecal chemotherapy.
• Relapsed/Refractory Disease – May require novel therapies or stem cell transplantation.

Prognosis and Follow-Up

• Prognosis is better in children, with cure rates exceeding 80%.
• Adults have a lower survival rate, especially in high-risk subtypes.
• Long-term follow-up includes:
  • Monitoring for late effects of chemotherapy (e.g., secondary malignancies, cardiotoxicity).
  • Surveillance for relapse with periodic blood tests and bone marrow biopsies.

Key Takeaways for Junior Doctors

1. Consider ALL in patients with pancytopenia and circulating lymphoblasts.
2. Early initiation of supportive care, including infection control and TLS prophylaxis, is crucial.
3. ALL management involves multiple chemotherapy phases and is highly protocol-driven.
4. Recognising complications such as febrile neutropenia and mediastinal masses can be life-saving.
5. Palliative care is an important consideration for patients unsuitable for intensive therapy.

ALL is a complex but treatable disease, particularly with advances in targeted therapies and stem cell transplantation. Junior doctors play a key role in initial diagnosis, supportive care, and recognising complications.

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