1. 1 Chronic Leukemia Dr.Huad alkarim.

2. 2 What Are the Types of Chronic Leukemia?

3. 3 Classification of CL. There are two types: There are two types: – 1-chronic myeloid leukemia. – 2-chronic lymphoid leukemia.

4. 4 Chronic Myeloid Leukemia.

5. 5 Definition of CML: Is a clonal disorder of a pluripotent stem cell and is classified as one of the myeloproliferative disorder. Is a clonal disorder of a pluripotent stem cell and is classified as one of the myeloproliferative disorder. Constitute six different types of leukemia. Constitute six different types of leukemia. See table. See table.

6. 6 Types of Chronic CML: Typename 1 (CML,Ph+)(chronic granulocytic leukemia) 2(CML,Ph-) 3 Juvenile CML 4 Chronic neutrophilic leukemia. 5 Esinophilic leukemia 6 Chronic myelomonocytic leukemia

7. 7 Cont: The disease accounts for around 15% of leukemia. The disease accounts for around 15% of leukemia. May occur at any age. May occur at any age.

8. 8 What Is Philadelphia Chromosome?

9. 9 Philadelphia : Is the chromosome which result from the t(9;22)(q34;q11)  part of the Abelson proto- oncogene ABL is moved to the BCR gene on chromosome 22 & part of chromosome 22 moves to chromosome 9. Is the chromosome which result from the t(9;22)(q34;q11)  part of the Abelson proto- oncogene ABL is moved to the BCR gene on chromosome 22 & part of chromosome 22 moves to chromosome 9. The abnormal chromosome 22is the Ph. The abnormal chromosome 22is the Ph. See fig. See fig.

10. 10 Fig

11. 11 How Would the Patient With CML Present?

12. 12 Clinical Presentation: It can occur in any age.But the most age presentation is between 40-60. It can occur in any age.But the most age presentation is between 40-60. Symptoms related to hyper metabolism: Symptoms related to hyper metabolism: (weight loss,lassitude,anorexia or night sweats). (Gout or renal impairment caused by hyperuriceamia ). Bone marrow failure: Bone marrow failure:Anemia.

13. 13 Cont: Bruising,epistaxis,menorrhagia or hemorrhage from any site because of platelet dysfunction. Bruising,epistaxis,menorrhagia or hemorrhage from any site because of platelet dysfunction. Organ infiltration: Organ infiltration: Splenomegally almost always present and is frequently massive. Rare symptoms include visual disturbance.

14. 14 How Would You Investigate the Patient With Suspected CML? ….

15. 15 Investigation: CBC: CBC: Wbc is usually >50X10/l & some times >500X10/l. Normocytic normochromic anemia. Platelets . peripheral blood film: peripheral blood film:  circulating basophil.

16. 16 fig

17. 17 Cont: Neutrophil alkaline phosphatase score is invariably low. Neutrophil alkaline phosphatase score is invariably low. BM: is hyper cellular with granulopoietic predominance. BM: is hyper cellular with granulopoietic predominance. Cytogenetics: ph chromosome. Cytogenetics: ph chromosome. Serum vitamin B12 & vitamin b12-binding capacity are . Serum vitamin B12 & vitamin b12-binding capacity are . Serum uric acid is usually . Serum uric acid is usually .

18. 18 What Are the Phases of CML? …

19. 19 Phases of CML: Chronic phase : Chronic phase : Accelerated phase: Accelerated phase: Blast phase: Blast phase:

20. 20 How Would You Treat CML? …

21. 21 Treatment: Chemotherapy: Chemotherapy: Tyrosine kinase inhibitor: Tyrosine kinase inhibitor: Interferon- . Interferon- . Stem cell transplant. Stem cell transplant.

22. 22 What Is the Course and Prognosis of CML?..

23. 23 Course & prognosis: Usually shows excellent response to chemtherapy in the chonic phase. Usually shows excellent response to chemtherapy in the chonic phase. Death usually occur from terminal acute trasformation,hemorrhage or infection. Death usually occur from terminal acute trasformation,hemorrhage or infection.

24. 24 Take a Break ! …

25. 25 Chronic lymphocytic Leukemia:

26. 26 Introduction: CLL is the most common of the chronic lymphoid leukemias. CLL is the most common of the chronic lymphoid leukemias. Peak incidence between 60-80yrs. Peak incidence between 60-80yrs. It is characterize by chronic persistent lymphocytosis which later infiltrate different organs. It is characterize by chronic persistent lymphocytosis which later infiltrate different organs.

27. 27 What Is the Clinical Presentation?

28. 28 Clinical presentation: The disease occurs in older subject,rare before 40yrs. The disease occurs in older subject,rare before 40yrs. M:F is 2:1. M:F is 2:1. Many cases discover routinely. Many cases discover routinely. Symmetrical enlargement of superficial lymph node is the most frequent clinical sign. Symmetrical enlargement of superficial lymph node is the most frequent clinical sign. Feature of anemia. Feature of anemia.

29. 29 Fig(1)

30. 30 Cont: Splenomegaly & hepatomegaly usual in later stage. Splenomegaly & hepatomegaly usual in later stage. Repeated bacterial or fungal infection. Repeated bacterial or fungal infection. Thrombocytopenia. Thrombocytopenia.

31. 31 Fig(2)

32. 32 How would you investigate patient with CLL?..

33. 33 Investigation: CBC: CBC: – Wbc: . – Diff:lymphocytosis,the absolute lymphocyte count is>5x10 9 /l and may be up to 300x10 9 /l or. More. Anemia:normocytic normochromic anemia is present in later stages,autoimmune haemolysis. Platelets : thrombocytepenia may occur.

34. 34 Cont: Blood film: 70-99% of white cells mature lymphocyte. Smudge or smear cells also present. Immunophenotyping: Shows that the lymphocyte are B cells(CD19)expressing one form of light chain(  or only)cells are also CD5&CD23+ve.

35. 35 Fig(3)

36. 36 Cont: Bone marrow aspiration: Bone marrow aspiration: Lymphocytic replacement of normal marrow. Immunoglobulinelectrophoresis: Immunoglobulinelectrophoresis:  of Ig more marker with advance disease. Cytogenetic : Cytogenetic : The 4 most common abnormalities are; deletion of13q14,trisomy 12,deletion of11q23&structural abnormality of 17p involving the p53 gene.

37. 37 What Is the Staging of CLL? …

38. 38 Staging : Staging is very important for prognosis and treatment. Staging is very important for prognosis and treatment. There are two staging system(Rai and Binet). There are two staging system(Rai and Binet). See table. See table.

39. 39 A-Rai Classification: Stagedefinition 0 Absolute lymphocytosis >15x10 9 /l. 1 Stage 0+enlarged lymph nodes. 11 Stage 0+liver or/and spleen   adenopathy. 111 Stage 0+anemia  organomegally or adenopathy. 1V Stage 0+thrombocytopenia  organomegally or adenopathy.

40. 40 B-Binet Classification: Stage. Organomegally. HbPlatelet. A(50-60%)0,1,or2areas B(30%) 3,4,or 5areas  10  100 C(<20%) Not considered <10 and /or <100 and /or <100

41. 41 How Would You Treat Patient With CLL? …

42. 42 Treatment : Since cure is rare,the treatment aim is only symptoms control. Since cure is rare,the treatment aim is only symptoms control. Indication for treatment: Indication for treatment: – Troublesome organomegaly. – Hemolytic episodes. – Bone marrow suppression.

43. 43 Modality of Treatment: 1-chemotherapy: 1-chemotherapy: Chlorambucil: 6mg/m 2 daily for 10 days monthly for 2-4 month after which remission will be obtain. Fludarabine:more effective as single agent. Corticosteroid :indicated in bone marrow failure,also indicated in autoimmune hemolytic anemia and thrombocytopenia.

44. 44 Cont: 2-Radiotherapy: 2-Radiotherapy: Is useful in reducing the size of lymphnode not responsive to chemo. 3-Monoclonal antibody: 3-Monoclonal antibody: Both campath IH(anti CD52)and Rituximab(anti CD20)produce response in proportion of patient.

45. 45 Cont: 4-Splenectomy : 4-Splenectomy : For immune-mediated cytopenia or painful bulky splenomegally. 5-immunoglobulin replacement: 5-immunoglobulin replacement: 250mg/kg /month by IV for patient with hypogammaglobulinemia and recurrent infection.

46. 46 Cont: 5- Stem cell transplant: 5- Stem cell transplant: Under clinical trial.

47. 47 Good Luck! ……..