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)
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 leukemia
- 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
- 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 leukemia.
- Low Hb with anaemia and Low platelets
- U&E: may be raised creatinine
- Serum uric acid levels raised and raised serum LDH
- Bone marrow aspiration ad biopsy examination - hypercellular > 20% blasts. Send for flow cytometric full immunophenotypic characterization and
molecular analyses
- LP and CF examination to look for CNS involvement
- Imaging studies to assess bulk disease (e.g., CT scan of chest &
abdomen)
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. Consider drugs to lower uric acid - Allopurinol and Rasburicase.
- Pneumocystis prophylaxis starting with
the second course of chemotherapy. Granulocyte colony-stimulating
factor (G-CSF) may be used.
- Induction chemotherapy - clears the marrow of blast cells - vincristine, Prednisolone, asparaginase and daunorubicin
- Consolidation - further reduces tumour burden
- CNS: usually high dose methotrexate is given which crosses the blood-brain barrier. Otherwise, intrathecal drugs may be given. Radiation may be needed.
- Maintenance therapy for several years
- Supportive measures prior to treatment especially to avoid tumour lysis syndromes with good hydration and Allopurinol and to watch for hyperkalaemia
- Those who fail chemotherapy may be considered for BMT
- 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