Acute Leukemia Samed Al-Ameri, BSc MLT.

1. Acute LeukemiaSamed Al-Ameri, BSc MLT.

2. Headline • Definition • Etiology • Pathophysiology • Classification • Clinical Manifestations • Diagnostic Studies

3. Leukemia Definition • A group of malignant disorders affecting the blood and blood-forming tissues of • Bone marrow • Lymph system • Spleen • Results in an accumulation of dysfunctional cells because of a loss of regulation in cell division

4. Leukemia Etiology • No single causative agent • Most from a combination of factors: • Genetic and environmental influences • Chemical agents • Chemotherapeutic agents • Viruses • Radiation • Immunologic deficiencies

5. Pathophysiology

7. Stage 1- Normal Stage 2- Symptoms Stage 3- Diagnosis Stage 5a- Anemia Stage 4- Worsening Stage 5b- Infection Development of Leukemia in the Bloodstream Legend White Cell Red Cell Platelet Blast Germ Sources from Leukemia, by D. Newton and D. Siegel

8. leukemia Classification Main classification Acute leukemia Chronic leukemia Lymphoid (CLL) Myeloid (CML) Lymphoid (ALL) Myeloid (AML)

9. Acute Leukemia

10. FAB criteria Morphology Cytochemistry WHO criteria Morphology Immunophenotyping Genetic features Karyotyping Molecular testing Clinical features Acute LeukemiaClassifications FABvs. WHO

11. Acuteleukemia FAB Classification (1976) Acute leukemia Lymphoid (ALL) Myeloid (AML) L1 Homogenous small lymphoblasts; mostly in children L2 Large heterogeneous blasts; mostly in adults L3 -Burkett's large basophilic B-cell blasts with vacuoles M0 - Undifferentiated M1myeloblastic undifferentiated M2myeloblastic with differentiaion M3promyelocytic M4myelomonocytic M5monoblastic M6erythroleukaemia M7megakaryoblastic

12. WHO Classification of AML • AML with recurrent genetic abnormalities • AML with multilineage dysplasia • AML therapy related • AML not otherwise categorised • AML of ambiguous lineage

13. WHO classification of ALL

14. ALL germinal center B-lymphocytes Plasma cells Lymphoid progenitor T-lymphocytes Neutrophils AML Myeloid progenitor Eosinophils Hematopoietic stem cell Basophils Monocytes Platelets Red cells

15. Signs and Symptoms • Most of the signs and symptoms are due to: 1-Anemia. 2-Leukopenia. 3-Thrombocytopenia. • Bicytopenia, Pancytopenia. • All symptoms associated with leukemia can be attributed to other diseases, consequently, leukemiais always diagnosed by laboratory investigations.

16. Acute Lymphoblastic Leukaemia • Cancer of the blood affecting the white blood cell known as LYMPHOCYTES. • Commonest in the age 2-10 years • Peak at 3-4 years. • Incidence decreaseswith age, and a secondary rise after40 years. • In children - most common malignant disease • 85% of childhood leukemia

17. Acute Lymphoblastic Leukemia • Specific manifestation : *Bone pain, arthritis * Lymphadenopathy *Hepatosplenomegaly *Mediastinal mass *testicular swelling *Meningeal syndrome

18. Acute Myeloid Leukemia • Arise from the malignant transformation of a myeloid precursor • Rare in childhood (10%-15%) • The incidence increases with age • 80% in adults • Most frequent leukemia in neonate

19. Acute Myeloid Leukemia • Specific manifestation : - Gum hypertrophy • Hepatosplenomegaly • Skins deposit • Lymphadenopathy • Renal damage • DIVC mainly in (M3)

20. Diagnostic Studies Diagnosis • Morphology • Cytochemistry • Immunophenotyping • Cytogentics

21. Laboratory Findings CBC: • WBC:60% of pts have an elevated WBC. WBC count in acute leukemia can be high, normal, or low. ALL: • WBC usually elevated (20,000- 100,000 / cmm ). • 20% of pts have 50,000 / cmm • 90%have blast in the peripheral blood film. AML: • Median WBC count in AML is 15000/ cmm. • 20% of patients have > 100,000/cmm. • 25-40% of patients have <5000/cmm. • 95% of patients have blast cells on blood film. • Most are anemic, Anemia (normochromic, normocytic) • Most are thrombocytopenic, Thrombocyte <100,000/mm3

22. Laboratory Findings • Electrolytes: • Hypo/hyper kalemia • Hypomagnesaemia • hyperphosphatemia • Hypermetabolism: • LDH. • uric acid. • Abnormal Coagulation Test (DIC) • LFT, RFT

23. Platelet Platelet White Cell Red Cell Red Cell Blasts White Cell Normal human blood Blood with leukemia Pictures Of Blood Sources from beyond2000.com Sources from Arginine.umdnj.edu

24. Bone marrow biopsy and aspirate: • 20%or more of all nucleated cells are blast. • ALL (Lymphoblast) • Blast size :small • Cytoplasm: Scant • Chromatin: Dense • Nucleoli :Indistinct • Auer-rods: Never present • AML (Myeloblast) • Large • Moderate • Fine, Lacy • Prominent • Present in 50%

25. Bone marrow smear Normal Bone marrow ALL AML

26. Acute Myeloid Leukaemia – Auer Rod

27. Bone marrow biopsy

28. The Cytochemistry ______________________ALL____________AML__________ • Myeloperoxidase - + • Suddan black - + • Non-specific esterase - + in M4, M5 • Periodic acid Schiff (PAS) + in c-ALL + in M6 • Acid phosphatase + in T-ALL + in M6

29. The Cytochemistry Periodic acid Schiff (PAS) positive ALL Peroxidase positive AML Acid phosphatase -focal positive (T-ALL)

30. AML CD13 CD33 CD34 Glycophorin M6 Platelet Antigen M7 ALL B lineage CD19 CD22 CD10 T lineage CD7 CD3 CD2 CD5 Immunophenotyping

31. Cytogentics • Chromosomal abnormalities are found in the blasts in 70% of cases of AML and 90% of ALL • Important in the pathogenesis of the disease • Important for diagnosis • Prognostic implication

32. Cytogentics Common Chromosome Abnormalities Associated With Acute Leukemia • t(8;21) AML with maturation (M2) • t(15;17) AML-M3(APML) • Inv 16 AML-M4 • t(8;14) B-ALL • t(9;22) Chronic granulocytic leukemia • The Philadelphia chromosome : the product of a translocation between chromosomes 9 and 22 -confers a very poor prognosis in ALL.

33. Treatment • Supportive treatment • Chemotherapy • Blast Cell Transplantation

34. THANK YOU

35. ALL/L1 ALL/L2

36. ALL/L3

37. AML/M0 AML/M1

38. AML/M2 AML/M3

39. AML/M4 AML/M5

40. AML/M6 AML/M7