1. Haematological Malignancy leukaemia and lymphoma,myeloma Concepts and principles Medical Students 2010

2. Haematological Malignancies concern blood and lymphoid tissue Myelodysplasia (pre malignant) Acute leukaemia Chronic leukaemias Lymphoma Myeloma

3. Cancer cellsNormal cells Different growth patterns

4. 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

5. Naparstek, E. N Engl J Med 1995;333:516-518 A Possible Mechanism of Leukemic Transformation

6. apotosis Cells cycle and turn over Malignant cells Normal cells

7. Autophagy An concept of cell death avoidance

9. Chronic leukaemia Chronic myeloid leukaemia Chronic lymphatic leukaemia

10. Chronic Lymphatic Leukaemia (CLL) May present with mild lymphocytosis May have lymphadenopathy Hb 13.5g.dl, WCC 15x10 9 /l, platelets normal. Neutrophils 4x10 9 /l, lymphocytosis of 10x10 9 /l Immunophenotyping on peripheral blood is diagnostic Uniquely –biopsy not required

11. Mature B lymphocytes

12. 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

13. Chronic Myeloid leukaemia Typical count Hb 14.0g/dl WCC 120x10 9 /l Platelets 560x10 9 /l Neutrophils 114x10 9 /l

14. In CML raised WBC with some immature forms in the blood and often increased eosinophils and basophils. The predominant cell is the neutrophil.

15. Neutrophil Alkaline Phosphatase (NAP) low or absent

16. Marrow hypercellular with gross myeloid hyperplasia. Why is there so much growth? What’s driving it?

17. Translocation of long arm of 22 to long arm of 9.

18. 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

19. 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.

20. THYROSINE KINASE INHIBITORS Imatinib Desatinib Nilotinib All licenced in Ireland

24. Lymphoma Non Hodgkin’s Lymphoma Hodgkin’s Disease

25. NHL T cell B cell Histology/biopsy of node Radiology for staging Bone marrow for staging

26. NHL WHO and other classifications Aggressive –often curable Low grade-incurable but reasonable prognosis…

27. 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

28. Also ofatumumab – a fully humanised anti- CD20 in trials in CUH and elsewhere

29. Myeloma The malignant cell is the plasma cell Plasma cells secrete….. The malignant cell is clonal… Therefore the paraprotein is clonal… –A monoclonal gammopathy

30. Plasma cells in myeloma

32. Therapy of myeloma Chemotherapy Prednisolone and other steroids Thalidomide (angiogenesis inhibitors) Proteosome inhibitors Bortazemib Lenalidomide Experimental agents – include monoclonal antibodies

34. Myeloproliferative disorders Chronic myeloid leukaemia (CML) Polycythaemia rubra vera (PRV) Essential thrombocytosis (ET) Myelofibrosis (MF)

35. MYELOFIBROSIS