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Acute Lymphoblastic Leukaemia

Acute lymphoblastic leukaemia (ALL) is a type of blood cancer characterised by the overproduction of immature lymphocytes, known as lymphoblasts. This condition progresses rapidly and can be fatal within weeks or months if not treated.

Signs and Symptoms

Initial symptoms of ALL are often nonspecific, especially in children. Common signs include generalised weakness, fatigue, anaemia, dizziness, and frequent or unexplained fever and infections. Patients may also present with bone and joint pain, breathlessness, and enlarged lymph nodes, liver, or spleen. Other symptoms can include excessive bruising, petechiae, and weight loss. Central nervous system (CNS) involvement can manifest as headaches, vomiting, lethargy, neck stiffness, or cranial nerve palsies.

Causes and Risk Factors

The exact cause of ALL is typically unknown, but both genetic and environmental factors play a role. Genetic syndromes such as Down syndrome and Li–Fraumeni syndrome increase the risk. Environmental risk factors include significant radiation exposure and previous chemotherapy. Some hypothesise that an abnormal immune response to common infections may trigger the disease.

Diagnosis

Diagnosis begins with a medical history, physical examination, complete blood count, and blood smears. A bone marrow biopsy is essential for confirming ALL, typically showing >20% leukaemic lymphoblasts. A lumbar puncture can detect CNS involvement. Pathological examination, cytogenetics, and immunophenotyping (using techniques like flow cytometry) help classify the disease and predict its aggressiveness. Medical imaging can identify the spread of leukaemia to other organs.

Acute lymphoblastic leukaemia (ALL), peripheral blood of a child, Pappenheim stain, magnification x100
Peripheral blood smear showing ALL in a child, Pappenheim stain, magnification x100.

Treatment

Chemotherapy

Chemotherapy is the primary treatment for ALL, involving three phases: remission induction, intensification, and maintenance therapy. The goal is to reduce leukaemic blasts in the bone marrow to less than 5% and eliminate tumour cells from the blood. CNS prophylaxis with intrathecal chemotherapy or cranio-spinal irradiation is also essential to prevent CNS relapse.

Radiation Therapy

Radiation therapy is less commonly used today but may be indicated for painful bone lesions, high disease burdens, or as part of the preparation for a bone marrow transplant. CNS prophylaxis now relies more on intrathecal chemotherapy.

Biological and Immunotherapy

Biological therapies such as tyrosine-kinase inhibitors (e.g., imatinib) are used for specific ALL subtypes like Bcr-Abl1+ (Ph+) ALL. Immunotherapies, including chimeric antigen receptor (CAR) T-cell therapy, have shown promise. In 2017, the FDA approved tisagenlecleucel, a CAR-T therapy for refractory or relapsed B-cell ALL.

Two girls with ALL demonstrating intravenous access for chemotherapy
Two girls with ALL demonstrating intravenous access for chemotherapy.

Relapsed ALL

Patients with relapsed ALL generally have a poorer prognosis. Treatment typically involves reinduction chemotherapy followed by allogeneic bone marrow transplantation. Blinatumomab and dasatinib are other options that have shown efficacy in increasing remission rates.

Prognosis

Prognosis varies significantly based on several factors, including age, gender, ethnicity, and response to initial treatment. Children generally have a better prognosis, with an over 80% five-year survival rate in developed countries. Adults have a lower survival rate, with those over 70 years having a cure rate of just 5%. Genetic factors, such as the presence of the Philadelphia chromosome, also play a very important role in determining prognosis.

Overall survival rates at 5 years and 10 years in people in paediatric care and adults with ALL
Graphs of overall survival rates at 5 years and 10 years in paediatric and adult patients with ALL.

Self-assessment MCQs (single best answer)

What is the primary characteristic of Acute Lymphoblastic Leukaemia (ALL)?



Which of the following is a common initial symptom of ALL in children?



Which genetic syndrome is associated with an increased risk of developing ALL?



What is the essential diagnostic procedure to confirm ALL?



Which of the following treatments is the primary approach for ALL?



What type of therapy is used for CNS prophylaxis in ALL patients?



Which biological therapy is used for Bcr-Abl1+ (Ph+) ALL?



What is the prognosis for children with ALL in developed countries?



Which of the following is NOT a common symptom of CNS involvement in ALL?



What is a common treatment strategy for relapsed ALL?



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