The exact cause of acute lymphocytic leukemia (ALL) is not well understood, but several factors are known to contribute to its development:

• Genetic Factors:
  • Chromosomal abnormalities: Certain genetic changes, such as translocations (e.g., Philadelphia chromosome), inversions, and deletions, can increase the risk of ALL.
  • Inherited syndromes: Conditions like Down syndrome, Bloom syndrome, Li-Fraumeni syndrome, and Fanconi anemia are associated with a higher risk of ALL.
• Environmental Factors:
  • Radiation exposure: High levels of radiation, such as those from atomic bomb explosions or radiation therapy for other cancers, are linked to an increased risk of developing ALL.
  • Chemical exposure: Exposure to certain chemicals, like benzene (found in industrial settings) and some chemotherapy drugs used to treat other cancers, may increase the risk.
• Immune System Factors:
  • Weakened immune system: Individuals with weakened immune systems, whether due to inherited immune disorders, HIV/AIDS, or medications that suppress the immune system, may have a higher risk of developing ALL.
• Infections:
  • Viral infections: Although less common, some viral infections, such as Epstein-Barr virus (EBV) and Human T-cell leukemia virus-1 (HTLV-1), have been linked to an increased risk of leukemia.

While these factors can contribute to the development of ALL, most cases do not have a clear cause, and having one or more of these risk factors does not mean a person will develop the disease.

Pathophysiology of Acute Lymphocytic Leukemia (ALL)

The pathophysiology of ALL involves uncontrolled proliferation and accumulation of immature lymphoid cells (lymphoblasts) in the bone marrow, blood, and other tissues. The key aspects:

• Genetic mutations and chromosomal abnormalities:
  • Genetic mutations and chromosomal translocations (e.g., t(9;22) leading to the Philadelphia chromosome) disrupt normal cell growth and differentiation. These mutations often affect oncogenes, tumour suppressor genes, and genes involved in cell cycle regulation.
• Disruption of normal hematopoiesis:
  • The excessive proliferation of lymphoblasts in the bone marrow crowds out normal hematopoietic cells, leading to a decrease in the production of normal blood cells. This results in:
    • Anaemia: Due to a lack of red blood cells.
    • Thrombocytopenia: Due to a lack of platelets, leading to increased bleeding and bruising.
    • Neutropenia: Due to a lack of normal white blood cells, increasing the risk of infections.
  • Infiltration of other tissues:
    • Lymphoblasts can infiltrate other organs and tissues, including the liver, spleen, lymph nodes, central nervous system (CNS), and testes. This can cause:
      • Hepatosplenomegaly: Enlargement of the liver and spleen.
      • Lymphadenopathy: Swollen lymph nodes.
      • CNS involvement: Leading to headaches, seizures, or CN palsies.
      • Testicular involvement: Leading to testicular enlargement.
    • Metabolic Complications:
      • Rapid turnover of malignant cells can lead to metabolic abnormalities such as hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia, collectively known as tumour lysis syndrome (TLS).
    • Immune System Dysfunction:
      • The immune system's ability to fight infections is compromised due to the impaired function and production of normal lymphocytes and other immune cells.

General Symptoms

• Fatigue and weakness:  Due to anaemia from decreased red blood cell production.
• Fever: Often caused by infections due to neutropenia.
• Weight loss and loss of appetite

Hematologic Symptoms

• Pallor: Resulting from anaemia.
• Bleeding and bruising: Due to thrombocytopenia, leading to easy bruising, petechiae, epistaxis, and bleeding gums.

Bone and Joint Symptoms

• Bone Pain: Often in the long bones, due to bone marrow expansion.
• Joint Pain: Arthritis-like symptoms can occur due to leukemic infiltration.

Lymphatic Symptoms

• Lymphadenopathy: Enlarged, painless lymph nodes due to lymphoblast infiltration.

Abdominal Symptoms

• Hepatosplenomegaly: Enlarged liver and spleen due to infiltration of leukemic cells.

Neurological Symptoms

• Headaches, vomiting, and visual disturbances:  Due to CNS involvement, which can also cause cranial nerve palsies and seizures

Mediastinal Involvement (more typically seen in adolescent boys with T-ALL)

• Dyspnea and chest pain: Due to a mediastinal mass compressing the airways or vessels.
• Superior vena cava syndrome: Swelling and flushing of the face, neck, and upper extremities resulting from congestion due to superior vena cava compression by the mediastinal mass.

Other Symptoms

• Testicular Enlargement:  Infiltration of the testes by leukemic cells.
• Skin Lesions: Leukemia cutis characterised by infiltration of leukemic cells into the skin, causing nodules or rashes.

• Complete Blood Count (CBC):

• Anemia, thrombocytopenia, and variable white blood cell counts (can be low, normal, or high).
• Presence of blasts on peripheral smear.

• Bone Marrow Examination:

• Hypercellular marrow with a high percentage of lymphoblasts.

• Biochemical Abnormalities:

• Elevated uric acid and lactate dehydrogenase (LDH) levels due to rapid cell turnover.
• Abnormal liver and kidney function tests in advanced disease.

• Diagnostic Confirmation
• Cytogenetic and Molecular Analysis: involves identification of specific genetic abnormalities (e.g., Philadelphia chromosome) using techniques like Fluorescence in-situ Hybridization (FISH), Polymerase Chain Reaction (PCR), or karyotyping.
• Immunophenotyping: Flow cytometry to determine the lineage (B-cell or T-cell) and differentiation status of the lymphoblasts.

The management of acute leukemia is complex and requires a multidisciplinary approach involving haematologists, oncologists, nurses, and support staff. Continuous monitoring and adjustments to treatment plans are essential to achieve the best possible outcomes. There are three phases of treatment including;

Induction Therapy: This is to achieve complete remission by eradicating leukemic cells.

• Drugs: Typically, a combination of chemotherapy agents such as vincristine, corticosteroids (e.g., prednisone or dexamethasone), anthracyclines (e.g., daunorubicin), and asparaginase.

Consolidation Therapy: This is to eliminate residual disease and prevent relapse.

• Drugs: High-dose chemotherapy or additional cycles of similar drugs used in induction, sometimes including methotrexate and cytarabine.

Maintenance Therapy: The goal is to maintain remission and prevent relapse.

• Drugs: Lower-dose chemotherapy, usually including methotrexate and 6-mercaptopurine, for an extended period (often 2-3 years).

Central Nervous System (CNS) Prophylaxis: To prevent or treat CNS involvement.

• Methods: Intrathecal chemotherapy (e.g., methotrexate, cytarabine) and/or cranial irradiation.

Targeted Therapy: For specific genetic abnormalities (e.g., imatinib for Philadelphia chromosome-positive ALL).

Stem Cell Transplant: it is considered for high-risk patients or those who relapse.

• Infection Prevention and Management: Prophylactic antibiotics, antifungals, and antivirals; prompt treatment of infections.
• Transfusion Support: Red blood cells and platelets to manage anaemia and thrombocytopenia.
• Nutritional Support: Ensuring adequate nutrition during treatment.
• Psychosocial Support: Addressing the emotional and psychological needs of patients and their families.

NOTE: In case your facility is inadequately equipped (in terms of manpower and other supportive considerations) to manage such cases, early referral is warranted.

• Children: High cure rates, with long-term remission rates around 85-90%. Favourable prognostic factors: Younger age (1-10 years), lower initial white blood cell count, specific genetic features (e.g., TEL-AML1 translocation).
• Adults: Lower remission and cure rates compared to children. Prognosis worsens with increasing age, presence of high-risk genetic features (e.g., Philadelphia chromosome), and poor response to initial therapy.

Leukemia in children poses significant challenges in low-income settings due to limited access to diagnostic tools, chemotherapy, and supportive care. Early detection is often delayed, leading to poorer outcomes. Improving awareness, strengthening healthcare infrastructure, and providing affordable treatment options are essential for better management. Supportive care and early referral systems can help improve survival rates, making leukemia more manageable even in resource-limited environments.