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Haematological Malignancy leukaemia and lymphoma,myeloma Concepts and principles Medical Students. 2010. Haematological Malignancies concern blood and lymphoid tissue. Myelodysplasia (pre malignant) Acute leukaemia Chronic leukaemias Lymphoma Myeloma. Different growth patterns. - PowerPoint PPT Presentation
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Haematological Malignancyleukaemia and
lymphoma,myelomaConcepts and principles
Medical Students
2010
Haematological Malignancies concern blood and lymphoid
tissue
• Myelodysplasia (pre malignant)
• Acute leukaemia
• Chronic leukaemias
• Lymphoma
• Myeloma
Cancer cells Normal cells
Different growth patterns
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
Naparstek, E. N Engl J Med 1995;333:516-518
A Possible Mechanism of Leukemic Transformation
apotosis
• Cells cycle and turn over
• Malignant cells
• Normal cells
Autophagy
• An concept of cell death avoidance
Chronic leukaemia
• Chronic myeloid leukaemia
• Chronic lymphatic leukaemia
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
Mature B lymphocytes
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
Chronic Myeloid leukaemia
• Typical count
• Hb 14.0g/dl
• WCC 120x109/l
• Platelets 560x109/l
• Neutrophils 114x109/l
In CML raised WBC with some immature forms in the blood and often increased eosinophils and basophils . The predominant cell is the neutrophil.
Neutrophil Alkaline Phosphatase (NAP) low or absent
Marrow hypercellular with gross myeloid hyperplasia. Why is there so much growth? What’s driving it?
•Translocation of long arm of 22 to long arm of 9.
•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
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.
THYROSINE KINASE INHIBITORS
Imatinib
Desatinib
Nilotinib
All licenced in Ireland
Goldman, J. M. et al. N Engl J Med 2003;349:1451-1464
Signal-Transduction Pathways Affected by BCR-ABL
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
Lymphoma
• Non Hodgkin’s Lymphoma
• Hodgkin’s Disease
NHL
• T cell
• B cell
• Histology/biopsy of node
• Radiology for staging
• Bone marrow for staging
NHL
• WHO and other classifications
• Aggressive –often curable
• Low grade-incurable but reasonable prognosis…
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
Also ofatumumab – a fully humanised anti- CD20 in trials in CUH and elsewhere
Myeloma
• The malignant cell is the plasma cell
• Plasma cells secrete…..
• The malignant cell is clonal…
• Therefore the paraprotein is clonal…– A monoclonal gammopathy
Plasma cells in myeloma
Therapy of myeloma
• Chemotherapy
• Prednisolone and other steroids
• Thalidomide (angiogenesis inhibitors)
• Proteosome inhibitors Bortazemib
• Lenalidomide
• Experimental agents – include monoclonal antibodies
Tansey, W. P. N Engl J Med 2004;351:393-394
Prodding the Proteasome
Myeloproliferative disorders
• Chronic myeloid leukaemia (CML)
• Polycythaemia rubra vera (PRV)
• Essential thrombocytosis (ET)
• Myelofibrosis (MF)
MYELOFIBROSISMYELOFIBROSIS
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