Haematology for Doctors

Tag: T-ALL

  • Acute vs Chronic Leukaemia – A Brief Overview

    Acute vs Chronic Leukaemia – A Brief Overview

    Leukaemia is a group of malignancies affecting the bone marrow and blood, characterised by the uncontrolled proliferation of abnormal white blood cells. It is broadly classified into acute and chronic types, which differ significantly in presentation, pathophysiology, and management. This guide provides a structured overview to help junior doctors navigate the diagnosis and treatment of leukaemia.

    Classification of Leukaemia

    Leukaemias are divided based on cell lineage (myeloid vs lymphoid) and disease course (acute vs chronic):

    • Acute Myeloid Leukaemia (AML): Rapidly progressive cancer of myeloid progenitor cells.
    • Acute Lymphoblastic Leukaemia (ALL): Rapidly progressive cancer of lymphoid progenitor cells.
    • Chronic Myeloid Leukaemia (CML): Slow-growing cancer of myeloid cells.
    • Chronic Lymphocytic Leukaemia (CLL): Slow-growing cancer of lymphoid cells.

    Pathophysiology

    • Acute leukaemias arise from immature precursor cells (blasts), leading to uncontrolled proliferation and bone marrow failure.
    • Chronic leukaemias involve the accumulation of more mature but dysfunctional cells, leading to a slower disease progression.

    Clinical Presentation

    Acute Leukaemias (AML & ALL)

    • Rapid onset over weeks to months.
    • Symptoms of bone marrow failure, including anaemia (fatigue, pallor), neutropenia (infections), and thrombocytopenia (bleeding, bruising).
    • Systemic symptoms such as fever, weight loss, and night sweats.
    • ALL can involve the central nervous system (CNS), causing headaches, seizures, and neurological deficits.

    Chronic Leukaemias (CML & CLL)

    • Insidious onset over years, often detected incidentally on routine blood tests.
    • Fatigue, weight loss, and night sweats.
    • Lymphadenopathy and splenomegaly, especially in CLL.
    • CML may present with abdominal discomfort due to splenomegaly and a high white cell count.

    Investigations

    Acute Leukaemia

    • Full blood count (FBC): High or low white cell count with circulating blasts; anaemia and thrombocytopenia are common.
    • Blood film: Presence of blasts.
    • Bone marrow biopsy: Confirms diagnosis with >20% blasts.
    • Cytogenetics: Identifies translocations such as PML-RARA in acute promyelocytic leukaemia (APL).

    Chronic Leukaemia

    • FBC: Leukocytosis in CML; lymphocytosis in CLL.
    • Blood film: Smudge cells in CLL; left shift (immature myeloid cells) in CML.
    • Bone marrow biopsy: Hypercellular marrow with mature cells.
    • Cytogenetics: BCR-ABL fusion gene in CML.

    Management

    Acute Myeloid Leukaemia (AML)

    • Intensive chemotherapy with daunorubicin and cytarabine.
    • Bone marrow transplantation for high-risk or relapsed cases.

    Acute Lymphoblastic Leukaemia (ALL)

    • Multi-agent chemotherapy.
    • CNS prophylaxis with intrathecal methotrexate.
    • Bone marrow transplant for high-risk patients.

    Chronic Myeloid Leukaemia (CML)

    • First-line treatment with tyrosine kinase inhibitors (TKIs) such as imatinib or dasatinib.
    • Long-term suppression of disease with excellent survival rates.

    Chronic Lymphocytic Leukaemia (CLL)

    • Early-stage disease is often observed without treatment.
    • Symptomatic or high-risk disease is treated with targeted therapies like BTK inhibitors (ibrutinib) or BCL-2 inhibitors (venetoclax), often combined with monoclonal antibodies like rituximab or obinutuzumab.

    Prognosis

    • Acute leukaemias progress rapidly and require urgent treatment. Survival rates vary: AML has a 40-50% survival rate in younger patients but much lower in the elderly. ALL has a 70-90% survival rate in children but lower in adults.
    • Chronic leukaemias progress slowly and are often manageable for years. CML has an excellent prognosis with TKIs, with >90% five-year survival. CLL is highly variable, with some patients living decades without treatment.

    Key Takeaways for Junior Doctors

    • Acute leukaemias present with bone marrow failure and require urgent treatment.
    • Chronic leukaemias are often incidental findings and may not need immediate therapy.
    • Blasts in blood and bone marrow (>20%) suggest acute leukaemia.
    • CML is driven by BCR-ABL and treated with TKIs.
    • CLL is often indolent but requires treatment in high-risk cases.

    Leukaemia is a complex but fascinating field in haematology. Junior doctors play a vital role in recognising its presentation, initiating investigations, and understanding treatment pathways.

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  • Acute Lymphoblastic Leukaemia (ALL) – A Junior Doctor’s Guide

    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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