Makindo Medical Notes

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 affecting the blood and bone marrow. It is characterized by the overproduction of immature white blood cells called lymphocytes. ALL is the most common cancer in children, though it can also occur in adults. It is aggressive and progresses rapidly, requiring prompt treatment. Childhood ALL generally has a good prognosis, with many children achieving long-term survival.

About

• Most common leukaemia in children
• Typically affects children aged 2-4, but can occur at any age
• About 80% of children survive at least 5 years post-diagnosis

Risk Factors

• No identifiable cause in most cases
• Increased risk in children with Down syndrome (trisomy 21)
• Other risk factors include ataxia-telangiectasia and pesticide exposure

Aetiology

• Genetic damage may occur before birth
• Clonal proliferation of immature lymphoid cells (T or B lymphoblasts)
• B-cell markers: CD19, CD79a, CD10, CD34, TdT
• T-cell markers: CD7, CD3
• Lymphoblasts can be detected in blood and other tissues

WHO Classification of ALL

• Precursor B-ALL: CD19, CD79a, CD22
• Mature B-ALL: Surface IgM, cytoplasmic kappa/lambda chains
• T-lineage ALL: cyCD3 or sCD3 expression

FAB Classification of ALL

• L1: Small, uniform blasts with scant cytoplasm
• L2: Larger blasts with more cytoplasm and nucleoli
• L3: Large blasts with prominent nucleoli and basophilic cytoplasm

Clinical Features:Bone marrow failure

• Anaemia: Fatigue, tiredness
• Thrombocytopenia: Low platelets causing bleeding, bruising
• Leukopenia: Low white cells causing infections, fever
• Enlarged lymph nodes, spleen, or liver
• CNS involvement: Headache, confusion, cranial nerve palsies (in <5% of cases)

Investigations

• FBC: Abnormal WBC, low haemoglobin, low platelets; lymphoblasts in blood
• U&E: High creatinine, uric acid, and LDH levels
• Bone marrow biopsy: Confirms diagnosis with >20% blasts in the marrow
• Flow cytometry: Identifies specific markers on leukaemia cells
• Cytogenetic analysis: Detects genetic abnormalities for prognosis
• Imaging: CT scans or X-rays to assess disease extent

Differential Diagnosis

• Lymphoblastic lymphoma: Similar to ALL but <30% blasts in bone marrow; treated similarly

Management

• Resuscitation: ABC protocol, treat bone marrow failure, manage infections
• Supportive care: Blood transfusions, antibiotics, hydration, symptom management
• Chemotherapy: Main treatment, includes phases like induction, consolidation, and maintenance. Drugs include cytosine arabinoside, vincristine, prednisolone, asparaginase, and daunorubicin
• Prevent a CNS relapse: Give CNS chemotherapy or high dose methotrexate or brain radiotherapy
• Pneumocystis prophylaxis: Starts after second chemotherapy course
• Targeted therapy: Tyrosine kinase inhibitors for Philadelphia chromosome-positive cases
• Stem cell transplant: For patients who fail chemotherapy or are at high risk of relapse
• Immunotherapy: CAR T-cell therapy to modify T cells to target leukaemia

Prognosis

• Better prognosis: Hyperdiploidy, female sex, age >10 years, high WBC at diagnosis
• Poorer prognosis: Philadelphia chromosome, hypodiploidy, age <1 or >50, high initial WBC count (>50,000)