Acute leukemias

acute leukemia, acute myeloblastic leukemia, acute lymphoblastic leukemia, WHO classification

1. LEUKEMIAS Acute leukemias

2. What you will learn now? Definition Types Differences between myloblasts and lymphoblasts Pathogenesis( leukemogenesis) Morphology Clinical features Lab findings

3. Leukemias are the group of disorders characterized by malignant transformation of the blood forming cells It may involve any of the cell lines or a stem cell common to several cell lines.

4. Leukemias are classified into 2 major groups Acute Onset is usually rapid, The disease is very aggressive, The cells involved are usually poorly differentiated with many blasts. Chronic Onset is insidious, The disease is usually less aggressive, The cells involved are usually more mature cells

5. Both acute and chronic leukemias are further classified according to the prominent cell line involved in the expansion: If the prominent cell line is of the myeloid series it is a MYELOCYTIC LEUKEMIA (sometimes also called granulocytic) If the prominent cell line is of the lymphoid series it is a LYMPHOCYTIC LEUKEMIA

6. Therefore, there are four basic types of leukemia Acute myelocytic leukemia – AML Acute lymphocytic leukemia – ALL Chronic myelocytic leukemia – CML Chronic lymphocytic leukemia – CLL

7. Etiology the exact cause is frequently not known, but predisposing factors are known Host factors Environmental factors

8. Etiology the exact cause is frequently not known, but predisposing factors are known Host factors Some individuals have an inherited increased predisposition to develop leukemia There is an increased incidence in those with an inherited tendency for chromosome fragility or abnormality or those with increased numbers of chromosomes (such as Down’s syndrome). Many of these diseases are characterized by chromosomal translocations.

9. There is an increased incidence in those with hereditary immunodeficiencies. There is an increased incidence in those with chronic marrow dysfunction such as those with myeloproliferative diseases, myelodysplastic syndromes, aplastic anemia, or paroxsymal nocturnal hemoglobinuria.

10. Environmental factors: Exposure to ionizing radiation Exposure to mutagenic chemicals and drugs Viral infections

11. Incidence Acute leukemias can occur in all age groups ALL is more common in children AML is more common in adults Chronic leukemias are usually a disease of adults CLL is extremely rare in children and unusual before the age of 40 CML has a peak age of 30-50

12. Comparison of acute and chronic leukemias: Acute Chronic Age all ages usually adults Clinical onset sudden insidious Course (untreated) 6 mo. or less 2-6 years Leukemic cells immature >20% blasts more mature ` cells Anemia prominent mild Thrombocytopenia prominent mild WBC count variable increased Lymphadenopathy mild present;often prominent Splenomegaly mild present;often prominent

13. Acute leukemia - pathogenesis Is a result of: Malignant transformation of a stem cell leading to unregulated proliferation and Arrest in maturation at the primitive blast stage. Remember that a blast is the most immature cell that can be recognized as committed to a particular cell line.

14. Leukemic proliferation, accumulation, and invasion of normal tissues, including the liver, spleen, lymph nodes, central nervous system, and skin, cause lesions ranging from rashes to tumors. A humoral mediator from the leukemic cells may inhibit proliferation of normal cells. Failure of the bone marrow and normal hematopoiesis may result in pancytopenia with death from hemorrhaging and infections.

15. Acute leukemias AML and ALL FAB classification AML( 8 subtypes M0 to M7 ) ALL ( L1 to L3 )

16. Myeloblasts with auer rods the MYELOBLAST is a large blast with a moderate amount of cytoplasm, fine lacey chromatin, and prominent nucleoli. 10-40% of myeloblasts contain auer rods

17. Lymphoblast in contrast to the myeloblast, the LYMPHOBLAST is a small blast with scant cytoplasm, dense chromatin, indistinct nucleoli, and no auer rods

18. Cytochemical stains Myeloperoxidase Sudan black Periodic acid schiff(PAS) Non specific esterase Acid phosphatase Myeloblasts( except M0) Immature cells in AML Lymphoblasts , erythroblasts Monocytic ( M4 M 5) Monocytic cells and focally in lymphoblasts

19. FAB Acute Myeloid Leukemia M0 Minimally differentiated AML 5% - 10% Negative or < 3% blasts stain for MPO ,PAS and NSE blasts are negative for B and T lymphoid antigens, platelet glycoproteins and erythroid glycophorin A. M1 Myeloblastic without maturation 10 - 20% >90% cells are myeloblasts 3% of blasts stain for MPO +8 frequently seen

20. M2 AML with maturation 30 - 40% 30% - 90% are myeloblasts ~ 15% with t(8:21)

21. M3 Acute Promyelocytic Leukemia (APML) 10-15% Auer rods/ faggot cells may be seen Granules contain procoagulants (thromboplastin-like) - massive DIC t(15:17) is diagnostic  

22. M4 Acute Myelomonocytic Leukemia 10-15% Incresed incidence CNS involvement Monocytes and promonocytes 20% - 80%

23. M5a Acute Monoblastic Leukemia 10-15% M5b AMoL with differentiation <5% Often asso with infiltration into gums/skin Weakness, bleeding and diffuse erythematous skin rash

24. M6 Erythroleukemia (Di Guglielmo) <5% 50% or more of all nucleated marrow cells are erythroid precursors, and 30% or more of the remaining nonerythroid cells are myeloblasts

25. M7 Acute Megakaryoblastic Leukemia <5% Assoc with fibrosis

26. FAB Acute Lymphoblastic Leukemia Acute lymphoblastic leukemia L-1 85% L-2 14% L-3 (Burkitt's)1% childhood

27. ALL L1 Homogenous small lymphoblasts Scant cytoplasm Regular round nuclei Inconspicuous nucleoli

28. ALL L2 Heterogenous lymphoblasts Variable cytoplasm Cleft nuclei Large nucleoli

29. ALL L3 Homogenous large lymphoblasts Vacuolated cytoplasm Round nuclei

30. Clinical features Bone marrow failure Organ infiltration Pallor, lethargy, dyspnea Bleeding manifestations Infections fever Pain & tenderness of bones Lymphadenopathy Hepatosplenomagaly Gum hypertrophy Chloromas Meningeal signs

31. Lab findings 1. Blood picture RBC WBC Platelets 2. Bone marrow 3. Cytochemistry 4. Cytogenetics

32. FAB vs WHO Classifications of Hematologic Neoplasm FAB criteria Morphology Cytochemistry WHO criteria Morphology Immunophenotyping Genetic features Karyotyping Molecular testing Clinical features

33. WHO Classification of AML AML with recurrent cytogenic translocations AML with multi-lineage dysplasia AML and myelodysplasia, therapy related AML, not otherwise categorized

34. Summary Definition Types Differences between myloblasts and lymphoblasts Pathogenesis( leukemogenesis ) Morphology Clinical features Lab findings WHO classification

35. Thank you