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Acute Leukaemia

Acute Leukaemia. Dr. Soheir Adam, MRCPath Assistant Professor Department of Haematology, KAUH. Acute Lymphoblastic Leukaemia. ALL is a malignant clonal disorder in which early lymphoid precursors proliferate and replace normal marrow cells. Pathophysiology

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Acute Leukaemia

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  1. Acute Leukaemia Dr. Soheir Adam, MRCPath Assistant Professor Department of Haematology, KAUH

  2. Acute Lymphoblastic Leukaemia • ALL is a malignant clonal disorder in which early lymphoid precursors proliferate and replace normal marrow cells. • Pathophysiology Lymphoid precursors are arrested in the early stages of development. This arrest is caused by an abnormal expression of genes, often due to chromosomal translocations.

  3. Acute Lymphoblastic Leukaemia • Incidence - ALL is the most common cancer of childhood - In adults it is more common in men - It is less common in adults than AML

  4. Acute Lymphoblastic Leukaemia • Presentation - Symptoms related to depletion of normal marrow elements e.g. anaemia, bleeding - Bone pain due to infiltration of bone marrow by leukaemic cells - Organomegaly: splenomegaly - T-ALL can present with a mediastinal mass - Fever and/or weight loss

  5. Acute Lymphoblastic Leukaemia • Physical Examination - Signs of anaemia / infection - Lymphadenopathy / organomegaly - Petechiae / ecchymosis due to low platelets - Signs of CNS or testicular involvement - Less commonly signs of hyperleukostasis like mental confusion and headache

  6. Acute Lymphoblastic Leukaemia • Laboratory Investigation - CBC - Peripheral smear - LDH and uric acid - LFT - U&Es - Blood cultures

  7. Acute Lymphoblastic Leukaemia • Radiological Investigation - CXR - Chest CT - Abdominal US - ECG & MUGA scan

  8. Acute Lymphoblastic Leukaemia • Bone marrow aspiration & trephine biopsy - Morphology - Cytochemistry - Flowcytometry - Cytogenetic analysis • Lumbar puncture • Testicular ultrasound

  9. Acute Lymphoblastic Leukaemia • Cytochemical Stains - Myeloperoxidase negative - Tdt positive • Immunophenotyping - Detects B or T antigens expresed on the surface of blast cells =, antibodies are given CD numbers - Some ALL cells co-express myeloid markers

  10. Acute Lymphoblastic Leukaemia • Cytogenetic Analysis - Determines prognosis and determines treatment plan - Bad prognostic chromosomal abnormalities e.g. t(9,22), t(4,11), t(8,14), t(2,8) & t(8,22) - Good prognosis with oter abnormalities e.g. t(10,14), hyperdiploidly > 50 and near tetraploidy - Philidelphia chromosome t(9,22) is found in 10- 15% of adults and 2-5% of children with ALL

  11. Acute Lymphoblastic Leukaemia Management • 1 - Chemotherapy - Induction - Consolidation - Late intensification - Maintenance

  12. Acute Lymphoblastic Leukaemia Management • 2 – CNS prophylaxis - Intrathecal chemotherapy - Cranial irradiation - Systemic chemotherapy - If CNS disease  IT chemotherapy twice weekly until 3 consecutive clear CSF samples

  13. Acute Lymphoblastic Leukaemia Management • 3 – Bone marrow transplantation - Offered to young patients with high risk features who are in first remission - Young patients with no high risk features should be considered for BMT when in relapse - Older patients should be offered non- myeloablative BMT within clinical trials

  14. Acute Lymphoblastic Leukaemia Management • 4 – Mature B-ALL - Burkitt-like leukaemia - Not considered for early transplant as before - Special chemotherapy protocols are used in such cases - Hyper-CVAD regimen produces 81% CR and 61% event-free survival at 3 years

  15. Acute Lymphoblastic Leukaemia Management • 5 – Supportive care - PRBCs transfusion if Hb < 9 g/dl - Platelets transfusion if < 20,000 or if patient is actively bleeding - Antibiotics for febrile neutropenia (gram negative organisms coverage) - Growth factors reduce the nadir and duration of neutropenia - Pneumocystis carinii prophylaxis

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