Makindo Medical Notes.com

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 a type of cancer that affects the blood and bone marrow. It is characterized by the overproduction of immature lymphocytes, a type of white blood cell. ALL is the most common type of cancer in children, but it can also occur in adults. It is an aggressive disease that progresses rapidly and requires prompt treatment. Classifications are useful in allowing standardisation of diagnosis and assessing the benefits of different treatment regimens. Childhood ALL is associated with a good prognosis.

About

• Commonest leukaemia seen in Children
• Any age but usually age 2-4.
• Potentially curable in some - 80% alive at 5 years

Risks

• Most have no link to a cause
• Children with Down syndrome (trisomy 21)
• Ataxia-telangiectasia have an increased risk;
• Exposure to pesticides

Aetiology

• Clonal proliferation of cells from early stages of lymphoid maturation. T or B blasts
• B cell blasts - CD19, CD79a, CD10, CD34, terminal deoxynucleotide transferase
• T cell markers CD7, CD3
• Blast cells are detectable in the peripheral circulation and other tissues

Classification of the of ALL (WHO)

• Precursor B ALL: CD19 and/or CD79a and/or CD22
• Mature B-ALL - surface IgM, and cytoplasmic kappa or lambda light chains (This is the former L3 variant or Burkitt’s leukaemia
• T-lineage ALL characterized by expression of cyCD3 or sCD3.

FAB classification of ALL

• L1 - uniform small blasts with scanty cytoplasm. The nucleus occupies the whole cell, has condensed chromatin and nucleoli are not seen
• L2 - large blasts with more nucleoli and cytoplasm. The chromatin around the nucleolus is condensed. The cytoplasm is pale blue, forms a rim around the nucleus and does not contain any inclusions
• L3 - Large blasts, prominent nucleoli basophilic cytoplasm (High LDH and tumour lysis syndrome commoner). There are 1-2 prominent nucleoli, cytoplasm is moderate in amount blue in colour and there are punched out vacuoles in the cytoplasm and overlying the nucleus

Clinical: Most symptoms relate to bone marrow replacement with leukaemia

• Anaemia - tiredness, fatigue
• Thrombocytopenia, Low platelets - bleeding and petechiae and bruising
• Leucopenia (High WCC also seen) Low WCC - infections and sepsis, Otitis media, pharyngitis, pneumonia, fever
• Bulk disease: Lymphadenopathy, splenomegaly, Hepatomegaly, Mediastinal mass
• CNS involvement - headache, confusion and cranial nerve palsies in < 5%

Investigations

• FBC: Low/high WCC and peripheral blood film may show circulating lymphoblasts. Rarely high WCC may be seen. Rarely the count may be low in subleukaemic leukaemia. Low Hb with anaemia and Low platelets
• U&E: may be raised creatinine and serum uric acid levels raised and raised serum LDH
• Bone marrow biopsy and aspiration: Definitive test shows hypercellular marrow > 20% blasts.
• Flow Cytometry: A test that analyzes the types of cells in the blood or bone marrow to identify specific markers on the leukaemia cells. Allows full immunophenotypic characterization and molecular analyses
• Cytogenetic Analysis: Detects genetic abnormalities in the leukaemia cells, which can help determine the prognosis and guide treatment.
• Imaging Studies: CT scans, X-rays, or ultrasounds may be used to assess the extent of the disease or to detect complications like an enlarged spleen or liver

Differential

• Lymphoblastic lymphoma - less of a blast in peripheral blood. <30% blasts in marrow. Treated same as ALL

Management

• ABC, Manage bone marrow failure. Resuscitate. Treat any sepsis.
• Supportive Care: transfusions, antibiotics, and other treatments to manage symptoms and complications.
• Chemotherapy: The main treatment for ALL. Use multiple drugs to kill leukaemia cells. It is usually given in several phases: induction, consolidation, and maintenance therapy. Give drugs to lower uric acid - Allopurinol and Rasburicase.
• Pneumocystis prophylaxis starting with the second course of chaemotherapy. Granulocyte colony-stimulating factor (G-CSF) may be used.
• Targeted Therapy: e.g. tyrosine kinase inhibitors for patients with the Philadelphia chromosome.
• Induction chaemotherapy - clears the marrow of blast cells - vincristine, Prednisolone, asparaginase and daunorubicin. Then Consolidation - further reduces tumour burden. CNS disease needs high dose methotrexate which crosses the blood-brain barrier. Otherwise, intrathecal drugs may be given. Radiation may be needed. Maintenance therapy for several years. Ensure supportive measures prior to treatment especially to avoid tumour lysis syndromes with good hydration and Allopurinol and to watch for hyperkalaemia
• Bone marrow Transplant: Those who fail chaemotherapy or have a high risk of relapse
• Immunotherapy: CAR T-cell therapy is an emerging treatment that modifies the patient’s T cells to attack leukaemia cells.

Prognosis

• Better Prognosis : Hyperdiploidy, Female, High WCC at presentation, Age > 10
• Worse Prognosis: Philadelphia chromosome found in 5% ALL, Rearrangements of the mixed-lineage leukaemia/lymphoma gene, Hypoploidy, age < 1 years or > 50-60 years, Initial WCC > 50,000