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Chronic leukaemias

Chronic leukaemias. Chronic myelogenous leukaemia Chronic lymphocytic leukaemia. Chronic leukaemias. Chronic myelogenous leukaemia Chronic lymphocytic leukaemia. Chronic myelogenous leukaemia. A Myeloproliferative disorder

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Chronic leukaemias

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  1. Chronic leukaemias Chronic myelogenous leukaemia Chronic lymphocytic leukaemia

  2. Chronic leukaemias Chronic myelogenous leukaemia Chronic lymphocytic leukaemia

  3. Chronic myelogenous leukaemia • A Myeloproliferative disorder • A clonal disorder where 95% of patients have a distinctive cytogenetic abnormality “the Philadelphia (Ph) chromosome” • Median age of ph+ CML is 67 yrs(30-80yrs) • Medial survival is 4-6 yrs, (range 1-10yrs) • Curative only by BMT

  4. Myeloproliferative disorders • Chronic myelogenous leukaemia • Polycythemia Vera • Myelofibrosis • Essential thrombocythemia

  5. CML – Natural History • Chronic phase: • Disease respond to treatment • < 5% of blasts and promyelocytesin the peripheral blood and bone marrow • Accelerated phase • > 5% in either peripheral blood or bone marrow and < 20% in both peripheral blood and bone marrow. • Blast crisis  acute leukaemia • > 20% blasts are present in peripheral blood or bone marrow • 70% AML • 30% ALL

  6. CML- Symptoms • Fatigue • Abdominal fullness and discomfort • Symptoms of anaemia • Night sweating • Low grade fever • When WBC count is very high “leukostasis” • Blurred vision • Respiratory distress • priapism

  7. CML- Signs Splenomegaly ; mild to gross, usually marked 10% have normal spleen Sternal tenderness Signs of anaemia

  8. Philadelphia chromosome • A cytogenetic abnormality • Due to reciprocal translocation between the long arm of chromosomes 9(9q) and 22(22q) (9:22 translocation) • It is found in all haematopoietic precursors of CML patients. • This result in the transfer of the Abelson's (abl) oncogene to an area of chromosome 22 termed the break-point cluster region (bcr) • This results in a fused bcr-abl gene and production of an abnormal tyrosine kinase protein. • This protein causes disordered myelopoiesis in CML

  9. CML- Investigations • Complete blood count • Peripheral blood film smear • Bone marrow aspiration • Ph chromosome analysis • Others

  10. CML- Investigations • Complete blood count • Peripheral blood film smear • Bone marrow aspiration • Southern Blot analysis • Ph chromosome analysis • NAP score • Others

  11. Complete blood count •  WBC counts • It may reach up to 500 x 109/l • Usually around 150 x 109/l • Anaemia • Platelets N or 

  12. CML- Investigations • Complete blood count • Peripheral blood film smear • Bone marrow aspiration • Ph chromosome analysis • Others

  13. Peripheral blood film smear Shift to left of myeloid series with more myelocytes in PBF than mature WBCs Blast cells are < 5% Basophilia

  14. PBF in CML

  15. CML- Investigations • Complete blood count • Peripheral blood film smear • Bone marrow aspiration • Assess cellularity • Assess fibrosis • Cytogenetic studies for Ph chromosome analysis • Others

  16. CML - Bone marrow aspiration • Hyper cellular bone marrow • Shift in the myeloid series to immature forms, this increase in number as patients progress to blastic phase of the disease. • Myeloblastcount <5% of myeloid cells in chronic phase. • Elevated myeloid/ erythroid ratio in the marrow.

  17. CML- Investigations • Complete blood count • Peripheral blood film smear • Bone marrow aspiration • Assess cellularity • Assess fibrosis • Cytogenetic studies for Ph chromosome analysis • Others •  Vitamin B12 level due to  secretion of transcobolamin III •  Uric acid

  18. Management of Chronic CML • Gleevec® (Imatinib mesylate) • A tyrosine kinase inhibitor • Tyrosine kinase is required for transforming functioin of the bcr-able fusion protein • It induces hematological remission in almost all patients with interferon resistent CML • Cytogenetic response is seen in 50% of patients.

  19. Management of Chronic CML • Allogenic BMT • Is the only curative treatment available of CML so far • It should be considered in the first year of diagnosis if the patient is <40 yrs of age and has an HLA matched donor. • Interferon α • Used for patients who are not eligible for BMT • May induce a cytogenetic response in 20% of patients.

  20. Management of Chronic CML • Hydroxurea • Uses: • Initial treatment to lower WBC count prior to interferon therapy. • Palliative treatment of patients failing other treatment. • Splenectomy • Hypersplenism • discomfort

  21. Accelerated phase of CML • Features • Bone pain • Spleenomegaly • Resistance to current treatment • Progressive anaemia • Thrombocytopenia or thrombocytosis • Blast cells >5% in either PB or BM and <30% of both PB and BM.

  22. Accelerated phase of CML • Treatment • Imatinibmesylate • Bone marrow transplantation • High dose cytarabine

  23. Blastic phase of CML • Features • Fever • Malaise • Progressive splenomgaly • Blast cells >20% in PB or BM

  24. Blastic phase of CML • Treatment • Imatinibmesylate • As in ALL (Vincrisitneand prednisolone +anthracycline) • AllogenicBMT

  25. Chronic lymphocytic leukemia • It is a disease of morphologically mature but immunologically less mature lymphocytes. • Manifested by progressive accumulation of lymphocytes in the blood, bone marrow and lymphatic tissues.

  26. CLL • Epidemiology • The most common leukemia in adult • males >females • > 45 yrs • Here mature lymphocytes fail to respond to Ag stimulation • 95% are B cell type • 5% are T cell type • The overall 5 year survival is 60%

  27. Indolent lymphocytosis (asymptomatic) Generalized lymphadenopathy Hepato-splenomegaly CLLClinical presentation

  28. Pancytopenia Anaemia Coombs positive hemolysis Hypoplastic Bleeding Production thrombocytopenia Immune thrombocytopenia Infection Depressed immunoglobulin levels CLLClinical presentation

  29. CLLinvestigations • CBC • PBF • BM aspiration • Immunochemistry • Total protein and Ig level

  30. CLLinvestigations • CBC • PBF • BM aspiration • immunochemistry • Total protein and Ig level

  31. Complete blood counts • WBC: • Increased counts • Mainly lymphocytes • Lymphocyte count >=10 x 109/l • Hb: • Normal or low • Hemolytic anaemia • Platelets: • Normal or low

  32. CLLinvestigations • CBC • PBF • BM aspiration • Immunochemistry • Total protein and Ig level

  33. Perioheral blood film • Predominantly lymphocytosis • Normally looking • Presence of smudge cells

  34. CLLinvestigations • CBC • PBF • BM aspiration • Immunochemistry • Total protein and Ig level

  35. Bone marrow aspiration • Not necessary for diagnosis • Infiltration of the bone marrow by lymphocytes.

  36. CLLinvestigations • CBC • PBF • BM aspiration • Immuno chemistry • Total protein and Ig level

  37. Immunoglobulin levels Immuno-chemistry • Low immunoglobulin levels • CD19 positive • CD20 positive • CD5 positive

  38. CLL- staging

  39. CLLwhom to treat? • Stage A  No Treatment • Observation only • Stage B  Treat if symptomatic • Observation only for asymptomatic • Chemotherapy for symptomatic lymphadenopathy • Stage C  Treat All • Should be treated

  40. CLLtreatment • Supportive treatment • Treat infection • Herpes zoster • Pseudomonas carinii • Proper hydration + allopurinol • Automimmuneanaemia or thrombocytopenia • corticosteroids • Blood transfusion • High dose immuneglobulin • Cyclosporine • Splenectomy • Low dose radiation to the spleen

  41. CLLTreatment options • Oral alkylating agents + corticosteroids • Chlorambucil+ prednisolone • Purine analogues: Fludrabine, • Combination chemotherapy: • CVP or CHOP • Involved field radiotherapy: for lymph node areas • Splenic radiation for palliation of hypersplenism

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