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Leukaemia

Leukaemia. Dr. Maria Krutikov FY1 Tuesday 15 th Nov 2011.  Cancer affecting bone marrow and blood causing uncontrolled proliferation of cells at different stages of proliferation. Lymphocytic vs Myelogenous. Lymphocytic affects lymphoid marrow that form lymphocytes

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Leukaemia

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  1. Leukaemia Dr. Maria Krutikov FY1 Tuesday 15th Nov 2011

  2.  Cancer affecting bone marrow and blood causing uncontrolled proliferation of cells at different stages of proliferation

  3. Lymphocytic vs Myelogenous • Lymphocytic affects lymphoid marrow that form lymphocytes • Myelogenous affects myeloid marrow that forms red blood cells, platelets and white blood cells

  4. Acute vs Chronic • Acute causes number of blasts (young immature, non-functional) to increase rapidly and crowd out functional cells in marrow and enter circulation • Chronic affects non-functioning mature cells that slowly increase in number and eventually crowd out functional cells  Can develop into ACUTE leukaemia

  5. Risk Factors • Smoking • Radiation exposure • Downs syndrome • Past chemotherapy • Exposure to Hydrocarbons • Myelodysplasia

  6. Presentation

  7. 4 Main Types: • Acute Lymphocytic (lymphoblastic) ALL • Acute Myelogenous (myeloid) AML • Chronic Myelogenous (myeloid) CML • Chronic Lymphocytic (lymphoblastic) CLL

  8. ALL • Most common in children • 550 new cases / year (UK) • Survival – 85% in children, 35% in adults • 30 % have Ph chromosome – poor prognosis • Radiotherapy + Chemotherapy +/- stem cell transplant

  9. Presentation Marrow failure: Infiltration: AnaemiaHbhepatosplenomegaly Infection – neutropenialymphadenopathy Bleeding + orchidomegaly CNS involvement ie. CN palsy, meningism Infection - mouth, perianal, chest, skin, Herpes Zoster, Candida, measles, CMV

  10. Treatments • Supportive: Transfusion, IV fluids, Allopurinol (prevent tumour lysis), Hickmann line • Chemotherapy: different regimens • BMT

  11. AML • More commonly in adults and in men • Common complication of chemotherapy • 5 year survival – 40% • Chemotherapy +/- stem cell transplant • Philadelphia chromosome • BCR-ABL gene t(9,22) – produce aggressive tyrosine kinase that prevents myelocytes from developing into neutrophils

  12. AML Marrow failure: thrombocytopenia, neutropenia, anaemia, leucostasis (resp distress + altered mental status), DIC - cytokines released that alctivate clotting cascade forming microemboli Organ infiltration • C/O dizziness, SOB, early satiety, petechiae, bruises, gingivitis, bone pain, fever, infection • Can cause gout as plasma URATE increases – give allopurinol + hydrate • Hyperviscosity – increased risk stroke / MI • Auer rods – crystals of coalesced granules

  13. Supportive • Chemotherapy – long term (5 cycles in 1/52 blocks, induce remission) • Tyrosine Kinase inhibitor • BMT

  14. Acute promyelocytic leukaemia – t(15;17) release of thromboplastin, present w DIC and treated with Vitamin A to switch off the gene

  15. CML • Uncontrolled clonal proliferation myeloid cells • Mainly in adults + males • Slow progression -> splenomegaly • Philadelphia chromosome in 80% • Treated w immunomodulators ie. Imatinib (Glivec) • 5 year survival – 90%

  16. Chronic + insiduous:  weight loss, fatigue, fever, sweats gout features, bleeding, anaemia, bruising, abdo discomfort – hepatosplenomegaly • No lymphadenopathy as myeloid do not mature in lymph nodes • ↑WCC , ↓Hb, ↑urate and B12 • Hypercellular bone marrow • Use Imatinib (Glivec) or Stem cell transplant

  17. CLL • Monoclonal proliferation of non-functioning mature B cells • Affects adults > 55 years, never children • 5 year survival – 75% • Incurable • Late defect in maturing lymphocyte • Very slow progression therefore splenomegaly + hepatomegaly + lymphaenopathy

  18. Infection + anaemia + severe sweats, weight loss and anorexia • Enlarged rubbery non-tender nodes, lymphatic obstruction, hepatosplenomegaly • Autoimmune haemolysis • Infection due to decreases IgG esp HZV • If present later - ↑WCC as at first WCC have not yet spilled over into blood

  19. Treatments NON-CURATIVE • Asymptomatic – monitor • Chlorambucil • Steroids – autoimmune haemolysis • Radiotherapy – relieve hepat/splenomegaly • Supportive – transfusions, IV human IgG

  20. Investigations • FBC + haematinics + U+Es + urate • Blood film • Bone marrow biopsy • CXR +/- CT (mediastinal /abdolymphadenopathy) • Flow cytometry- looks at antigen exression on cell surface to elicit stage of development of cells involved • FISH – fluorescent in situ hybridisation- fluorescently labelled DNA

  21. Treatments • Supportive – transfusions, IgG • Radiotherapy • Chemotherapy – vaying regimens • Biologic agents ie Glivec • Prophylactic – Abx • Bone marrow transplant – allogenic transplant from HLA matchingdonor

  22. Tumour lysis syndrome • Rapid cell death on starting chemo can cause rapid rise in URATE, POTASSIUM, PHOSPHATE causing renal failure • Need prevention with good hydration and allopurinol 24h before chemo

  23. Special considerations • Barrier nursing, side room, • Avoid IM injections – chance of infected haematoma • Avoid PR exams • Candida prophylaxis • Oral hygiene – hydrogen peroxidase mouthwash • Avoid cut flowers - pseudomonas

  24. Conclusions • Need to consider cells involved to predict symptoms • Variety of treatments available with new developments amongst biologic agents • Good prognosis in young • Should be in differential for PUO, weight loss, fatigue and neutropenia

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