Haematological Malignancy leukaemia and lymphoma,myeloma Concepts and principles Medical Students

1. Haematological Malignancyleukaemia and lymphoma,myelomaConcepts and principlesMedical Students 2010

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

3. Different growth patterns Cancer cells Normal cells

4. Acquired Capabilities, Molecular Pathways, and the Transformation of Human Cells: Emerging Rules That Govern Cancer Formation Hahn, W. C. et al. N Engl J Med 2002;347:1593-1603

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

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 15x109/l, platelets normal. Neutrophils 4x109/l, lymphocytosis of 10x109/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 120x109/l • Platelets 560x109/l • Neutrophils 114x109/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. Imatinib Desatinib Nilotinib All licenced in Ireland ThyrosineKinase inhibitors

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