Leukaemia

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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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LeukaemiaDr. Maria Krutikov FY1 Tuesday 15th Nov 2011 Cancer affecting bone marrow and blood causing uncontrolled proliferation of cells at different stages of proliferationLymphocytic vs Myelogenous
  • Lymphocytic affects lymphoid marrow that form lymphocytes
  • Myelogenous affects myeloid marrow that forms red blood cells, platelets and white blood cells
  • 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 Risk Factors
  • Smoking
  • Radiation exposure
  • Downs syndrome
  • Past chemotherapy
  • Exposure to Hydrocarbons
  • Myelodysplasia
  • Presentation 4 Main Types:
  • Acute Lymphocytic (lymphoblastic) ALL
  • Acute Myelogenous (myeloid) AML
  • Chronic Myelogenous (myeloid) CML
  • Chronic Lymphocytic (lymphoblastic) CLL
  • 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
  • PresentationMarrow failure: Infiltration:AnaemiaHbhepatosplenomegalyInfection – neutropenialymphadenopathyBleeding + orchidomegaly CNS involvement ie. CN palsy, meningismInfection - mouth, perianal, chest, skin, Herpes Zoster, Candida, measles, CMV Treatments
  • Supportive: Transfusion, IV fluids, Allopurinol (prevent tumour lysis), Hickmann line
  • Chemotherapy: different regimens
  • BMT
  • 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
  • AMLMarrow failure: thrombocytopenia, neutropenia, anaemia, leucostasis (resp distress + altered mental status), DIC - cytokines released that alctivate clotting cascade forming microemboliOrgan 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
  • Supportive
  • Chemotherapy – long term (5 cycles in 1/52 blocks, induce remission)
  • Tyrosine Kinase inhibitor
  • BMT
  • Acute promyelocytic leukaemia – t(15;17) release of thromboplastin, present w DIC and treated with Vitamin A to switch off the geneCML
  • 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%
  • 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 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
  • 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
  • Treatments NON-CURATIVE
  • Asymptomatic – monitor
  • Chlorambucil
  • Steroids – autoimmune haemolysis
  • Radiotherapy – relieve hepat/splenomegaly
  • Supportive – transfusions, IV human IgG
  • 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 DNATreatments
  • Supportive – transfusions, IgG
  • Radiotherapy
  • Chemotherapy – vaying regimens
  • Biologic agents ie Glivec
  • Prophylactic – Abx
  • Bone marrow transplant – allogenic transplant from HLA matchingdonor
  • 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
  • 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
  • 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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