Haematological Malignancy leukaemia and lymphoma,myeloma Concepts and principles Medical Students
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Transcript of Haematological Malignancy leukaemia and lymphoma,myeloma Concepts and principles Medical Students
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Haematological Malignancyleukaemia and
lymphoma,myelomaConcepts and principles
Medical Students
2010
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Haematological Malignancies concern blood and lymphoid
tissue
• Myelodysplasia (pre malignant)
• Acute leukaemia
• Chronic leukaemias
• Lymphoma
• Myeloma
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Cancer cells Normal cells
Different growth patterns
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Hahn, W. C. et al. N Engl J Med 2002;347:1593-1603
Acquired Capabilities, Molecular Pathways, and the Transformation of Human Cells: Emerging Rules That Govern Cancer Formation
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Naparstek, E. N Engl J Med 1995;333:516-518
A Possible Mechanism of Leukemic Transformation
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apotosis
• Cells cycle and turn over
• Malignant cells
• Normal cells
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Autophagy
• An concept of cell death avoidance
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Chronic leukaemia
• Chronic myeloid leukaemia
• Chronic lymphatic leukaemia
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Chronic Lymphatic Leukaemia (CLL)
• May present with mild lymphocytosis
• May have lymphadenopathy
• Hb 13.5g.dl, WCC 15x109/l, platelets normal. Neutrophils 4x109/l, lymphocytosis of 10x109/l
• Immunophenotyping on peripheral blood is diagnostic
• Uniquely –biopsy not required
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Mature B lymphocytes
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Therapy for CLL
• No therapy• Chemotherapy• Steroids• Immunotherapy: • Rituximab is a monoclonal antibody to CD20
which is expressed on all CLL cells. It is less toxic than chemotherapy and is effective in combination with chemotherapy drugs
• Ofatumumab
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Chronic Myeloid leukaemia
• Typical count
• Hb 14.0g/dl
• WCC 120x109/l
• Platelets 560x109/l
• Neutrophils 114x109/l
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In CML raised WBC with some immature forms in the blood and often increased eosinophils and basophils . The predominant cell is the neutrophil.
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Neutrophil Alkaline Phosphatase (NAP) low or absent
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Marrow hypercellular with gross myeloid hyperplasia. Why is there so much growth? What’s driving it?
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•Translocation of long arm of 22 to long arm of 9.
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•This results in activation of a hybrid bcr-abl proto-oncogene which can be detected by reverse transcriptase PCR
•This oncogene is critically dependant on thyrosine kinase to transmit its intracellular message
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Imatinib (Gleevec )….Time May 2001
Staying on Gleevec for life could cost a patient as much as $30,000 per year, though the mag predicts insurance companies will probably pick up the tab now that Gleevec's off the experimental list.
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THYROSINE KINASE INHIBITORS
Imatinib
Desatinib
Nilotinib
All licenced in Ireland
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Goldman, J. M. et al. N Engl J Med 2003;349:1451-1464
Signal-Transduction Pathways Affected by BCR-ABL
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Savage, D. G. et al. N Engl J Med 2002;346:683-693
Mechanism of Action of BCR-ABL and of Its Inhibition by Imatinib
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Lymphoma
• Non Hodgkin’s Lymphoma
• Hodgkin’s Disease
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NHL
• T cell
• B cell
• Histology/biopsy of node
• Radiology for staging
• Bone marrow for staging
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NHL
• WHO and other classifications
• Aggressive –often curable
• Low grade-incurable but reasonable prognosis…
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Treatment of Lymphomas
• Chemotherapy• Steroids• Immunotherapy: • Rituximab is a monoclonal antibody to CD20 which
is expressed on all CLL cells. It is less toxic than chemotherapy and is effective in combination with chemotherapy drugs
• Radiotherapy• Radio-immunotherapy (Yttrium-90)• Novel agents, lenalidomide,bortazemib
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Also ofatumumab – a fully humanised anti- CD20 in trials in CUH and elsewhere
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Myeloma
• The malignant cell is the plasma cell
• Plasma cells secrete…..
• The malignant cell is clonal…
• Therefore the paraprotein is clonal…– A monoclonal gammopathy
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Plasma cells in myeloma
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Therapy of myeloma
• Chemotherapy
• Prednisolone and other steroids
• Thalidomide (angiogenesis inhibitors)
• Proteosome inhibitors Bortazemib
• Lenalidomide
• Experimental agents – include monoclonal antibodies
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Tansey, W. P. N Engl J Med 2004;351:393-394
Prodding the Proteasome
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Myeloproliferative disorders
• Chronic myeloid leukaemia (CML)
• Polycythaemia rubra vera (PRV)
• Essential thrombocytosis (ET)
• Myelofibrosis (MF)
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MYELOFIBROSISMYELOFIBROSIS