A Glimpse into the World of Leukemia

1. A Glimpse into the World of Leukemia Jeffrey Bryan, Pharm.D. Clinical Pharmacy Specialist, Leukemia MD Anderson Cancer Center

3. Objectives • Describe the epidemiology, etiology and pathophysiology of acute and chronic leukemia • Discuss the presenting signs and symptoms of adult patients with acute and chronic leukemia • Summarize approaches to the diagnosis of leukemia • Compare the general approaches to the treatment of acute and chronic leukemia patients • Discuss the supportive care issues associated with acute and chronic leukemia patients

4. Leukemia: Epidemiology http://seer.cancer.gov/statfacts/html/leuks.html

5. Leukemia: Etiology • Chromosomal abnormalities/changes • Congenital disorders • Environmental factors • Family history • Chemical agents • Chemotherapeutic agents • Viruses

6. Leukemia: Pathophysiology • The pathophysiology of leukemia involves: Abnormal proliferation of leukocytes Failure of leukocytes to mature Metabolic complications • Abnormal leukocytes cannot perform the primary function • Abnormal cells crowd the bone marrow, lymph nodes, and spleen • Infection and bleeding are two common perils

7. Leukemia: Clinical Presentation

8. Leukemia: Clinical Problems

9. Leukemia: Approach to Diagnosis • Medical history and physical • CBC with differential • Chemistry panel • Bone marrow biopsy and aspiration • Immunophenotyping • Cytogenetics

10. Leukemia: Major Types • Acute Lymphocytic Leukemia (ALL) • Acute Myelogenous Leukemia (AML) • Chronic Lymphocytic Leukemia (CLL) • Chronic Myelogenous Leukemia (CML)

11. Leukemia: Diagnostic Categories FAB: French-American-British

12. Leukemia: Diagnostic Categories FAB: French-American-British

13. Acute Leukemias

14. Acute Leukemia: Blast Cells • Immature precursors of either lymphocytes (lymphoblasts), or granulocytes (myeloblasts) • Not normally appear in peripheral blood • Large size and primitive nuclei (i.e. the nuclei contain nucleoli) • Presence of Auer Rods • Special stains and surface marker techniques are needed to identify the lineage of the cells

15. ALL: Treatment Phases CNS Therapy (intrathecal chemotherapy)

16. AML: Treatment Phases

17. Acute Leukemia: Treatment Goals • Induction therapy Rapidly achieve complete response (CR) • Consolidation therapy Maintain CR Eliminate clinically undetectable leukemia Prevent/delay relapse • Maintenance therapy Eliminate residual leukemia Prolong remission • CNS therapy Prevent relapse

18. Acute Leukemia: Remission Criteria • Disappearance of all evidence of leukemia • Bone marrow: > 20% cellularity • Bone marrow: < 5% blasts • Absolute neutrophil count: > 1000 • Platelets: > 100x109/L

19. Acute Leukemia: Frontline Agents

20. Chronic Leukemias

21. CLL: Clinical Features of Staging

22. CLL: Treatment Phases

23. CLL: Response Criteria National Cancer Institute Working Group Criteria for complete remission in CLL

24. Chronic Leukemia: Frontline Agents

25. Chronic Myelogenous Leukemia

26. CML: Pathophysiology • CML arises from abnormal hematopoietic stem cells that give rise to progeny that have the Philadelphia chromosome (Ph) • Ph is created from the reciprocal translocation between chromosome 9 and 22 forming a BCR-Abl gene on a shortened chromosome 22 • Translocation is termed t(9;22)(q34.1;q11.2)

28. CML: Three Clinical Phases Disease Progression

29. CML: Clinical Presentation

30. CML: Treatment

31. CML: Response Criteria

32. CML: Tyrosine Kinase Inhibitors

33. Leukemia: Supportive Care Common Occasional Rare