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Leukaemia 101

Armaan Khalid. Leukaemia 101. What is Leukaemia?. Cancer of the blood or bone marrow Can be classified: Acute/chronic Myeloid/lymphoid. Classification of Leukaemias. Leukaemia. Acute. Chronic. ALL. AML. CLL. CML. Aetiology. ??? Radiation Survivors of Hiroshima & Nagasaki

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Leukaemia 101

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  1. Armaan Khalid Leukaemia 101

  2. What is Leukaemia? • Cancer of the blood or bone marrow • Can be classified: • Acute/chronic • Myeloid/lymphoid

  3. Classification of Leukaemias Leukaemia Acute Chronic ALL AML CLL CML

  4. Aetiology • ??? • Radiation • Survivors of Hiroshima & Nagasaki • Chemicals & drugs • Benzene, melphalan • Genetic • Down’s, Klinefelter’s • Viruses • Human T-cell lymphotropic virus type 1 (HTLV-1)

  5. Pic of cell lineage

  6. Acute Lymphoblastic Leukaemia • Malignant disease of BM in which early lymphoid precursors (lymphoblast) proliferate & replace normal haematopoetic cells • Normally due to chromosomal translocations • Lymphoblasts replace normal bone marrow production • Anaemia • Neutropaenia • Thrombocytopaenia

  7. Acute Myelogenous Leukaemia • Uncontrolled proliferation of myeloblasts in the bone marrow • Bone marrow overcrowding → failure • ♀<♂, affects all ages (↑↑↑ % with age) • Commonly due to • Chromosomal translocations • Genetic abnormalities (Down’s) • Radiation & chemical exposure (benzene) • Past exposure to chemo agents • Cancer survivors • Antecedent haematological disorder • Myelodysplastic Syndromes

  8. ALL/AML Presentation • ALL: Most common paeds malignancy • Hx/Ex • Fever • Fatigue/dizziness/palpitations/dyspnoea • Bleeding/Ecchymoses/Petechiae • Bone pain • Hepatosplenomegaly

  9. ALL/AML Workup • Ix • FBE/LDH/LFT/UNE • Peripheral blood film • Circulatory blast cells • Blood Culture • X-Ray/CT • Bone marrow aspiration & biopsy • Blast cells > 20% • Flow cytometry

  10. ALL/AML Mgmt • Chemotherapy • Induction • Consolidation • Maintenance • CNS prophylaxis (esp. ALL) • Risk of meningeal leukaemia @ diagnosis/relapse • FCR regimen • Fludarabine • Cyclophosphamide • Rituximab • G-CSF usage • BM transplantation

  11. Acute Promyelocytic Leukaemia • APML is a subtype of AML • Can be considered a medical emergency • Commonly assoc w coagulopathy due to DIC & fibrinolysis • Rule out by doing a peripheral blood smear

  12. Febrile Neutropaenia • Essential to monitor neutrophil count • Neutropaenia + Fever = Febrile Neutropaenia • Mgmt • Admit & isolate • Symptomatic Rx • Cease chemoRx • Broad spectrum Abx • E.g. Ticarcillin + Gentamicin • ?CSF administration

  13. Chronic Lymphocytic Leukaemia • Commonest Leukaemia (↑↑↑% in ↑ age) • Accumulation of functionally incompetent lymphocytes • Identical to Small Lymphocytic Lymphoma • Peripheral blood lymphocytosis > 4000 cells/mm3 • CLL • Almost always B lymphocytic in origin • Many pts are asymptomatic • Others present with BM failure & immunosuppresion

  14. CLL Presentation • Hx/Ex • Anaemia (AI haemolytic anaemia) • Fever • Generalised lymphadenopathy • Hepatosplenomegaly • Recurrent infection • Bleeding/Ecchymoses/Petechiae

  15. CLL Workup • Ix • FBE/LDH/LFT/UNE • Peripheral blood film • Lymphocytosis > 5 x 109/L for more 3 mth • Smudge cells • Blood Culture • X-Ray/CT • Bone marrow aspiration & biopsy • Blast cells > 20% • Flow cytometry • Lymph node biopsy

  16. Smudge cells in CLL

  17. CLL Mgmt • When to treat (Absolute indications) • Anaemia • Recurrent infection • Splenic discomfort • X2 lymphocyte count w/in 6 mth • ChemoRx • FCR/CHOP • BM transplantation • Transformation to more aggro tumours • Poor prognosis

  18. Chronic Myelogenous Leukaemia • Acquired abnormality that involves the haematopoetic stem cell • Characterised by ↑ proliferation of the granulocytic cell line w/out the loss of their ability to differentiate • On peripheral blood: ↑ granulocyte & its precursors w occasional blast cells • Philadelphia chromosome (9:22) • Almost always in adults (peak 40-60y/o) • Runs a slowly progressive course • Chronic phase • Accelerated phase • Blast crisis (Fatal)

  19. CML Blast Crisis • After 3-5 years, CML may evolve into a blast crisis • ↑↑↑ BM or peripheral blood blast count • Manifestation similar to acute leukaemia • Usual medication are unable to control leukocytosis & splenomegaly • 2/3 of cases are myeloid in nature • Accelerated phase may last 3-6 months prior to blast crisis

  20. Philadelphia chromosome

  21. Philadelphia chromosome 101 • Reciprocal translocation of b/w long arms of chromosomes 9 & 22 • Translocation causes relocation of abl oncogene (9) to the BCR region (22) • BCR/ABL fusion gene • Hallmark of CML however, can be found in other diseases (ALL)

  22. CML Presentation • Hx/Ex • Tiredness/Fatigue/LOW/Malaise • Hepatosplenomegaly • Low-grade fever & sweating • Anaemia • Lymphadenopathy

  23. CML Workup • Ix • FBE/LDH/LFT/UNE • ↓ Leukocyte alkaline phosphatase • Peripheral blood film • ↑ Granulocytes w myeloid precursors • Presence of different mid-stage progenitor cells • Blood Culture • X-Ray/CT • Bone marrow aspiration & biopsy • ↑ cellularity & myeloid precursors • Cytogenetic studies (Philadelphia chromosome) • Lymph node biopsy

  24. CML Mgmt • Goal • Haematological remission • Normal FBE • Cytogenetic remission • 0% Ph-positive cells • Molecular remission • Negative PCR for BCL/ABL gene • Imatinib (Gleevec) • Inhibits proliferation & induces apoptosis by inhibiting tyrosine kinase activity in cells positive for BCR/ABL fusion gene • Useful in Chronic phase

  25. CML Mgmt • Stem cell transplantation • Hydroxyurea • Myelosuppressive agent used to achieve haematological remission • Busulfan • Interferon • Splenectomy • Useful in pts with large & painful spleens, not managed well on medications

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