1. This lecture was conducted during the Nephrology Unit Grand Ground by Nephrology Registrar under Nephrology Division, Department of Medicine in King Saud University. Nephrology Division is not responsible for the content of the presentation for it is intended for learning and /or education purpose only.

2. Chronic Myeloid Leukemia
Balqis alabdulkarim

3. Chronic Myeloid Leukemia
Objectives:
Definition
Pathophysiology
Clinical presentation
Diagnosis.
Treatment

4. Chronic Myeloid Leukemia
Objectives:
Definition
Pathophysiology
Clinical presentation
Diagnosis
Treatment

5. What is CML Myeloproliferative disorder.
Increase proliferation of granulocytic cell line without losing their capacity to differentiate.
The peripheral blood cell profile shows an increased number of granulocytes and their immature precursors, including occasional blast cells.

6. What is CML
Single specific genetic mutation.
Philadelphia chromosome.

7. What is CML CML progresses through 3 phases: -Chronic -Accelerated
-Blast

8. What is CML
Epidemiology:
-Middle-aged (most)
-Younger and older

9. Chronic Myeloid Leukemia
Objectives:
Definition
Pathophysiology
Clinical presentation
Diagnosis
Treatment

10. Pathopysiology cytogenetic aberration in hematopoietic stem cell.
Translocation between the long arms of chromosomes 22 and 9 [t(9;22)].
 shortened chromosome 22.

12. Pathophysiology relocates an oncogene called ABL.
BCR/ABL fusion gene. (hallmark)

13. Pathiphysiology
Why did it happen?

14. Chronic Myeloid Leukemia
Objectives:
Definition
Pathophysiology
Clinical presentation
Diagnosis
Treatment

15. Clinical Presentation
Insidious.
Routine blood count: elevated white blood cell (WBC) count .
Non-Specific symptoms.
symptoms related to enlargement of the spleen and liver.
low-grade fever and excessive sweating related to hypermetabolism.

16. Clinical Presentation
Accelerated phase presentation:
 Bleeding, petechiae, and ecchymoses.
Fever
Infection
Bone pain

17. Clinical presentation
Physical examination:
Splenomegaly.
Hepatomegaly.
Leukostasis and hyperviscosity symptoms.

18. Chronic Myeloid Leukemia
Objectives:
Definition
Pathophysiology
Clinical presentation
Diagnosis.
Treatment

19. Diagnosis Blood Count and Peripheral Smear. Bone Marrow Analysis
Laboratory Abnormalities :
Hyperuricemia.
Markedly increased serum vitamin B12 binding protein.

20. Blood Count and Peripheral Smear
Increase in granulocytes 20,000-60,000 cells/μL
Mostly neutophiles, but there is a mild elevation in basophils and esophils.
No change in lymphocytes count, might exhibit a dilutional effect .
Normocytic normochromic anemia
Low platelets

21. Blood Count and Peripheral Smear

22. Bone Marrow Analysis
Hypercellular.
Mild fibrosis.

25. Chronic Myeloid Leukemia
Objectives:
Definition
Pathophysiology
Clinical presentation
Diagnosis.
Treatment

26. Treatment Goals of treatment: Hematologic remission.
Cytogenetic remission.
Molecular remission.

27. Treatment Tyrosine kinase inhibitor Myelosuppressive therapy.
Interferon alpha.
Transplantation.

28. Tyrosine Kinase Inhibitors
Imatinib is a tyrosine kinase inhibitor that inhibits the abnormal bcr-abl tyrosine kinase created by the Philadelphia (Ph1) chromosome translocation abnormality.
inhibits proliferation and induces apoptosis in cells positive for BCR/ABL

29. Tyrosine Kinase Inhibitors
Two newer BCR/ABL inhibitors, dasatinib and nilotinib.
More potent inhibitors of BCR/ABL than imatinib.
exhibit significant activity against almost all resistant mutations.

30. Myelosuppressive therapy
Myelosuppressive therapy was formerly the mainstay of treatment to convert a patient with CML from an uncontrolled initial presentation to one with hematologic remission and normalization of the physical examination and laboratory findings.
However, it may soon fall out of favor as the new agents prove to be more effective, with fewer adverse events and longer survival.

31. Interferon Alpha
In the past interferon alfa was the treatment of choice for most patients with CML whom bone marrow transplantation was not an option.
With the advent of tyrosine kinase inhibitors, interferon alfa is no longer considered first-line therapy for CML.
Used in combination with newer drugs for treatment of refractory cases

32. Transplantation
Allogeneic bone marrow transplantation or stem cell transplantation is currently the only proven cure for CML.
Young patients (< 55 yr)

33. Thank you!